Methods And Compositions For Inhibiting Polyomavirus-associated Pathology

Abstract

Disclosed herein are methods of eliciting an immune response against a polyomavirus (for example, BKV serotype I (BKV-I), BKV serotype II (BKV-II), BKV serotype III (BKV-III) and/or BKV serotype IV (BKV-IV)) and methods of treating or inhibiting polyomavirus-associated pathology (such as polyomavirus-associated nephropathy, BKV-associated hemorrhagic cystitis, or JC virus-associated progressive multifocal leukoencephalopathy; PML). Further disclosed are immunogenic compositions of use in the disclosed methods. Also disclosed are methods of selecting an organ transplant donor and/or recipient including detecting whether the prospective donor and/or recipient has BKV serotype-specific (such as BKV serotype IV-specific) neutralizing antibodies.

Description

CROSS REFERENCE TO RELATED APPLICATIONS

[0001] This is a divisional of U.S. patent application Ser. No. 14/233,582, filed Jan. 17, 2014, which is the U.S. National Stage of International Application No. PCT/US2012/047069, filed Jul. 17, 2012, which was published in English under PCT Article 21(2), which in turn claims the benefit of U.S. Provisional Application No. 61/508,897, filed Jul. 18, 2011, all of which are incorporated by reference herein in their entirety.

FIELD

[0002] This disclosure relates to the field of immunology, more specifically to methods and compositions for producing an immune response to polyomavirus, particularly BK polyomavirus.

BACKGROUND

[0003] The process of organ transplantation has been revolutionized since the first successful kidney transplant in identical twins more than five decades ago (Harrison et al., Surg. Forum 6:432-436, 1956; Merrill et al., J. Am Med. Assoc. 160:277-282, 1956). Since then, the use of immunosuppressants, such as cyclosporine, have improved the outcome of transplants (Caine, Mt. Sinai J. Med. 54:465-466, 1987), but the process is still fraught with many challenges, such as the management of chronic and acute rejection, nephrotoxicity from immunosuppressant and antiviral drugs, and avoiding reactivated (or novel) infectious agents that could threaten the graft. To balance these needs, clinical guidelines on the management of kidney transplant (Kasiske et al., Am. J. Transpl. 9:S1-S155, 2009) generally suggest the use of an immunosuppressant and an anti-proliferative agent in the initial stages of the process, followed by a lowering of dose of immunosuppressants if there is no acute rejection. However, careful monitoring of allograft function is crucial; and tests to detect increase in proteinuria, elevated serum creatinine levels, and detection of viral nucleic acids in plasma are also recommended.

[0004] One of the problems that threatens kidney allograft survival is the development of polyomavirus-associated nephropathy (PVAN) (Purighalla et al., Am. J. Kidney Dis. 26:671-673, 1995; also known as BKV associated nephropathy (BKVN)). Left untreated, PVAN can lead to a loss of the allograft, but early diagnosis, monitoring and intervention can prevent it. In kidney transplant recipients, current estimates of PVAN are about 1-10% (Ramos et al., Clin. Transpl. 2002:143-153; Hirsch et al., Transplantation 79:1277-1286, 2005), and graft losses range from 10-100% (Hirsch and Steiger, Lancet Inf. Dis. 3:611-623, 2003) depending on the drug regimen, monitoring, and interventions performed. Polyomavirus-associated pathologies such as PVAN or progressive multifocal leukoencephalopathy (PML) also cause significant morbidity or even mortality in other patients receiving immunosuppressive therapy (for example, for auto-immune disorders).

SUMMARY

[0005] Disclosed herein are methods of eliciting an immune response against a polyomavirus (for example, BKV serotype I (BKV-I), BKV serotype II (BKV-II), BKV serotype III (BKV-III), and/or BKV serotype IV (BKV-IV)) and methods of treating or inhibiting polyomavirus-associated pathology (such as PVAN, BKV-associated hemorrhagic cystitis, or JC virus-associated PML). Further disclosed are immunogenic compositions of use in the disclosed methods. In some embodiments, the immunogenic composition includes at least one capsid polypeptide (or a nucleic acid encoding such polypeptides) from two or more BKV serotypes (e.g., a multivalent immunogenic composition).

[0006] Also disclosed are methods of selecting a transplant donor and/or transplant recipient (for example a renal transplant donor or recipient) including detecting whether the prospective donor and/or recipient has BKV serotype-specific (such as BKV-IV-specific) neutralizing antibodies.

[0007] The foregoing and other features of the disclosure will become more apparent from the following detailed description, which proceeds with reference to the accompanying figures.

BRIEF DESCRIPTION OF THE DRAWINGS

[0008] FIG. 1 is a series of graphs showing ELISA and neutralizing antibody titers in mice immunized with virus-like particles (VLPs) formed by expression of recombinant VP1 capsid proteins derived from BKV-I isolate KOM-5 (subtype BKV-Ib1) or BKV-IV isolate A-66H (subtype BKV-IVc2). Six mice were immunized with BKV-I (circles) or BKV-IV (squares) VLPs. In the top panel, sera were titered using separate BKV-I (x axis) or BKV-IV (y axis) VLP ELISAs. A data point from one relatively non-responsive animal is shown as an open circle. The middle panel depicts BKV genotype-specific neutralizing titers for the same set of mice. The bottom panel shows the ratio of the neutralizing titer for the BKV genotype administered as a vaccine versus the neutralizing titer for the heterologous BKV genotype for individual animals. The non-responsive animal was excluded from the analysis in the bottom panel. In the top and middle panels, the diagonal line shows a theoretical 1:1 correlation between BKV-I and BKV-IV titers.

[0009] FIG. 2 is a series of graphs showing BKV-I and BKV-IV ELISA versus neutralizing titers in VLP immunized mice. ELISA (x axis) or neutralizing titers (y axis) for six BKV-I (circles) or BKV-IV (squares) VLP immunized mice are shown. Neutralizing titers against the BKV-I pseudovirus are shown in the left panel and anti-BKV-IV titers are shown in the right panel. A data point from the relatively non-responsive animal (FIG. 1) is shown as an open circle.

[0010] FIG. 3 is a pair of graphs showing BKV-I and BKV-IV serological titers in healthy adults. Sera from 48 healthy adults were evaluated for BKV type-specific serological titers. The upper panel shows BKV-I and BKV-IV titers evaluated by ELISA. The lower panel shows neutralizing titers. The diagonal line shows a theoretical 1:1 correlation between BKV-I and BKV-IV titers.

[0011] FIG. 4 is a series of graphs showing BKV-I and BKV-IV ELISA versus neutralizing titers in healthy adults. ELISA (x axis) or neutralizing titers (y axis) for BKV-I (circles) or BKV-IV (squares) are shown. Neutralizing titers against the BKV-I pseudovirus are shown in the left panel and anti-BKV-IV titers are shown in the right panel.

[0012] FIG. 5 is a series of graphs showing BKV-I and BKV-IV serological patterns in sera from individual kidney transplant recipients. Sera from kidney transplant recipients were titered for the presence of BKV-I (circles) or BKV-IV (squares) type-specific neutralizing titers (y axis). The neutralizing titer categories shown on the y axis are defined as: 1) <95% neutralization at a serum dilution of 1:100; 2) .gtoreq.95% neutralization at 1:100; 3) .gtoreq.95% neutralization at 1:500; 4) .gtoreq.95% neutralization at 1:5000; and 5) .gtoreq.95% neutralization at 1:50,000. Sera were collected at five different time points (x axis) spanning roughly 1, 4, 12, 26, and 52 weeks post-transplantation, designated A-E. In each panel, the notations in the bottom right corner represent the BKV genotype (I or IV) observed in the patient's urine (superscript u) or blood (superscript b). The subject denoted I/IV.sup.u showed urinary shedding of BKV-I at week 5 and urinary shedding of BKV-IV at week 16. The patterns of 12 representative patients are shown.

[0013] FIG. 6 is a series of graphs showing BKV-I and BKV-IV serological profiles in all 108 kidney transplant patients analyzed. Neutralizing titer categories (y-axis) and time points (x-axis) are as described for FIG. 5. The numbers at the top of each graph denote quantitation of BKV viruria (log10 BKV DNA copies per ml) at each time point. Dashes indicate that BKV DNA was not detected in the urine. The symbol "nr" indicates no results for the time point. The symbol "utq" indicates that the BKV viruria signal was too low for accurate quantitation. Asterisks mark time points at which BKV viremia was quantitated. The symbol JC+ indicates that JC virus DNA was detected.

[0014] FIG. 7 is a pair of graphs showing BKV-I and BKV-IV neutralizing titers in kidney transplant recipients at study entry and exit. Sera from 108 kidney transplant recipients were titered for the presence of BKV-I (top panel) or BKV-IV (bottom panel) type-specific neutralizing antibodies. The percentages of patients at a particular titer cut-off at study entry (one week after transplantation) are depicted as open bars, while the percentages of patients at a particular titer cut-off at study exit (one year post-transplantation) are depicted as filled bars.

[0015] FIG. 8 is a sequence alignment of BKV VP1 polypeptides. Because it is not possible to distinguish between Ia and IbIb1 subtypes based on VP1 amino acid sequences, BKV-Ia indicates genotypes Ia/Ib1 and BKV-Ib indicates genotype Ib2. It is also not possible to distinguish between BKV-IV subtypes based on VP1 amino acid sequences. Therefore, BKV-IV indicates genotypes IV-b1/IV-c2. Amino acids that are completely conserved among all BKV types are shaded. Sequence identifiers for the amino acid sequences are provided in Table 5 (below).

[0016] FIG. 9 is a phylogenetic tree showing the relationship of additional partial BKV VP1 sequences with selected BKV-I to BKV-IV VP1 sequences

[0017] FIG. 10 is a sequence alignment of BKV partial VP1 polypeptides (SEQ ID NOs: 126-158) with amino acids 31-174 of BKV-Ia (SEQ ID NO; 52), BKV-Ia (SEQ ID NO: 75), BKV-Ib2 (SEQ ID NO: 75), BKV-Ic (SEQ ID NO: 103), BKV-II (SEQ ID NO: 105), BKV-III (SEQ ID NO: 107), BKV-IVb1 (SEQ ID NO: 125), and BKV-IVc2 (SEQ IDNO: 124) polypeptides.

SEQUENCE LISTING

[0018] Any nucleic acid and amino acid sequences listed herein or in the accompanying sequence listing are shown using standard letter abbreviations for nucleotide bases and amino acids, as defined in 37 C.F.R. 1.822. In at least some cases, only one strand of each nucleic acid sequence is shown, but the complementary strand is understood as included by any reference to the displayed strand.

[0019] The Sequence Listing is submitted as an ASCII text file in the form of the file named Sequence_Listing.txt, which was created on Aug. 31, 2017, and is 380,503 bytes, which is incorporated by reference herein. [0020] SEQ ID NOs: 1-3 are amino acid sequences of exemplary BKV-Ib1 VP1, VP2, and VP3 proteins, respectively. [0021] SEQ ID NOs: 4-6 are amino acid sequences of exemplary BKV-IVc2 VP1, VP2, and VP3 proteins, respectively. [0022] SEQ ID NOs: 7-9 are amino acid sequences of exemplary BKV-II VP1, VP2, and VP3 proteins, respectively. [0023] SEQ ID NOs: 10-12 are amino acid sequences of exemplary BKV-III VP1, VP2, and VP3 proteins, respectively. [0024] SEQ ID NO: 13 is an exemplary BKV-Ia VP1 amino acid sequence. [0025] SEQ ID NO: 14 is an exemplary BKV-Ib2 VP1 amino acid sequence. [0026] SEQ ID NO: 15 is an exemplary BKV-Ic VP1 amino acid sequence. [0027] SEQ ID NO: 16 is an exemplary BKV-IV-b1 VP1 amino acid sequence. [0028] SEQ ID NOs: 17-19 are amino acid sequences of exemplary JCV-1A VP1, VP2, and VP3 proteins, respectively. [0029] SEQ ID NO: 20 is an exemplary JCV-2A VP1 amino acid sequence. [0030] SEQ ID NO: 21 is an exemplary JCV-3B VP1 amino acid sequence. [0031] SEQ ID NOs: 22-23 are exemplary JCV consensus VP2 and VP3 amino acid sequences, respectively. [0032] SEQ ID NOs: 24-26 are exemplary BKV-Ib1 VP1, VP2, and VP3 encoding nucleic acid sequences, respectively. [0033] SEQ ID NOs: 27-29 are exemplary BKV-IVc2 VP1, VP2, and VP3 encoding nucleic acid sequences, respectively. [0034] SEQ ID NOs: 30-32 are exemplary BKV-II VP1, VP2, and VP3 encoding nucleic acid sequences, respectively. [0035] SEQ ID NOs: 33-35 are exemplary BKV-III VP1, VP2, and VP3 encoding nucleic acid sequences, respectively. [0036] SEQ ID NOs: 36-38 are exemplary JCV-1A VP1, VP2, and VP3 encoding nucleic acid sequences, respectively. [0037] SEQ ID NOs: 39-41 are exemplary codon-optimized BKV-IVc2 VP1, VP2, and VP3 polypeptide encoding nucleic acid sequences, respectively. [0038] SEQ ID NO: 42 is an exemplary codon-optimized BKV-Ia VP1 polypeptide encoding nucleic acid sequence. [0039] SEQ ID NO: 43 is an exemplary codon-optimized BKV-Ib2 VP1 polypeptide encoding nucleic acid sequence. [0040] SEQ ID NO: 44 is an exemplary codon-optimized BKV-Ic VP1 polypeptide encoding nucleic acid sequence. [0041] SEQ ID NOs: 45 and 46 are exemplary codon-optimized BKV-II and BKV-III VP1 polypeptide encoding nucleic acid sequences, respectively. [0042] SEQ ID NO: 47 is an exemplary codon-optimized BKV-IVb1 VP1 polypeptide encoding nucleic acid sequence. [0043] SEQ ID NO: 48 is an exemplary codon-optimized JCV-2A VP1 polypeptide encoding nucleic acid sequence. [0044] SEQ ID NO: 49 is an exemplary codon-optimized JCV-3B VP1 polypeptide encoding nucleic acid sequence. [0045] SEQ ID NOs: 50 and 51 are exemplary codon-optimized JCV consensus VP2 and VP3 polypeptide encoding nucleic acid sequences, respectively. [0046] SEQ ID NOs: 52-125 are exemplary BKV VP1 polypeptide amino acid sequences. [0047] SEQ ID NOs: 126-160 are exemplary partial BKV VP1 polypeptide amino acid sequences.

DETAILED DESCRIPTION

[0048] BKV is a ubiquitous DNA virus and up to 90% of healthy individuals are seropositive. This virus is believed to initiate infection in the urinary tract and then remain latent without disturbing its host, with occasional reactivation in the form of low-level shedding of virions in the urine (viruria). However, in immunocompromised individuals BKV (and the related JC polyomavirus) can cause significant morbidity or even mortality.

[0049] In pediatric kidney transplants, being seronegative for BKV by a serological test before the procedure has been associated with developing PVAN. In adult kidney transplant recipients, it has been suggested that the role of donor BKV status plays a role in developing PVAN. However, pre-transplant BKV serology is not usually monitored; both because nearly all adults are believed to be seropositive for BKV, and because it has been generally believed that seropositivity for BKV is associated with protection against development of PVAN. Furthermore, the role of intravenous immunoglobulin (IVIG) in treating PVAN has been unclear.

[0050] BKV consists of four subgroups (or types; BKV-I, BKV-II, BKV-III, and BKV-IV) that have been equated with separate serotypes and have limited cross-reactivity as measured by hemagglutination inhibition (HI) and neutralization assays. However, the high BKV prevalence rates in humans, as measured by polymerase chain reaction or BKV seropositivity generally refer to serotype I only. The incidence of the other BKV types in patients prior to kidney or bone marrow transplant in Caucasians has been estimated to be about 3% for BKV-II, 6-7% for BKV-IV and undetectable for BKV-III. However, the present inventors have found a panel of sera from 48 healthy adults to be substantially higher than expected for genotypes II, III, and IV. In a few cases, the inventors have demonstrated that kidney transplant patients who initially had only BKV-I viruria later developed viruria and viremia (presence of virus in the bloodstream) with BKV-IV.

[0051] The cross-reactivity of anti-BKV antibodies between types has not been revisited since 1989; and it may have important implications in the development of PVAN in transplant patients, especially if the organ donor is positive for a less common BKV type. The present inventors have demonstrated that 23-43% of renal transplant patients with undetectable levels of BKV-IV neutralizing antibodies at the time of transplant seroconverted (changed from a negative result to a positive result in a serologic test) within one year, irrespective of their BKV-I serostatus. The small number of initially BKV-I seronegative renal transplant recipients all seroconverted for BKV-I, irrespective of their BKV-IV serostatus.

[0052] Thus, the inventors have demonstrated that presence of neutralizing antibodies against one BKV serotype does not protect from infection with other BKV serotypes, as was previously believed. Furthermore, the presence of neutralizing antibodies to BKV-Ib2 does not provide neutralization of BKV-Ia, demonstrating that not all BKV-I neutralizing antibodies can provide protection from all BKV-I subtypes. This indicates that vaccination of individuals (such as organ transplant recipients or other immunocompromised individuals) with a vaccine to a single BKV serotype or subtype may not effectively elicit an immune response to all serotypes or subtypes and may not provide adequate protection from polyomavirus-associated pathologies such as PVAN or PML. Furthermore, it indicates that the prevalence of BKV-I in the general population does not protect at risk individuals from infection with other BKV serotypes (such as BKV-IV).

I. Abbreviations

[0053] BKV BK polyomavirus [0054] BKV-I BKV serotype I [0055] BKV-II BKV serotype II [0056] BKV-III BKV serotype III [0057] BKV-IV BKV serotype IV [0058] ELISA enzyme-linked immunosorbant assay [0059] IVIG intravenous immunoglobulin [0060] JCV JC polyomavirus [0061] PML progressive multifocal leukoencephalopathy [0062] PVAN polyomavirus-associated nephropathy [0063] SV40 simian virus 40 [0064] VLP virus-like particle

II. Terms

[0065] Unless otherwise noted, technical terms are used according to conventional usage. Definitions of common terms in molecular biology may be found in Benjamin Lewin, Genes VII, published by Oxford University Press, 2000 (ISBN 019879276X); Kendrew et al. (eds.), The Encyclopedia of Molecular Biology, published by Blackwell Publishers, 1994 (ISBN 0632021829); Robert A. Meyers (ed.), Molecular Biology and Biotechnology: a Comprehensive Desk Reference, published by Wiley, John & Sons, Inc., 1995 (ISBN 0471186341); and George P. Redei, Encyclopedic Dictionary of Genetics, Genomics, and Proteomics, 2nd Edition, 2003 (ISBN: 0-471-26821-6).

[0066] The following explanations of terms and methods are provided to better describe the present disclosure and to guide those of ordinary skill in the art to practice the present disclosure. The singular forms "a," "an," and "the" refer to one or more than one, unless the context clearly dictates otherwise. For example, the term "comprising a polypeptide" includes single or plural polypeptides and is considered equivalent to the phrase "comprising at least one polypeptide." As used herein, "comprises" means "includes." Thus, "comprising A or B," means "including A, B, or A and B," without excluding additional elements.

[0067] All publications, patent applications, patents, and other references mentioned herein are incorporated by reference in their entirety for all purposes. In case of conflict, the present specification, including explanations of terms, will control.

[0068] Although methods and materials similar or equivalent to those described herein can be used to practice or test the disclosed technology, suitable methods and materials are described below. The materials, methods, and examples are illustrative only and not intended to be limiting.

[0069] To facilitate review of the various embodiments of this disclosure, the following explanations of specific terms are provided:

[0070] Antibody: A protein (or protein complex) that includes one or more polypeptides substantially encoded by immunoglobulin genes or fragments of immunoglobulin genes. The recognized immunoglobulin genes include the kappa, lambda, alpha, gamma, delta, epsilon, and mu constant region genes, as well as the myriad of immunoglobulin variable region genes. Light chains are classified as either kappa or lambda. Heavy chains are classified as gamma, mu, alpha, delta, or epsilon, which in turn define the immunoglobulin classes, IgG, IgM, IgA, IgD and IgE, respectively. A neutralizing antibody is an antibody which, on mixture with the homologous infectious agent (such as a polyomavirus), reduces the infectious titer. In some examples, a neutralizing antibody is an antibody that blocks the ability of its antigen to perform a physiological function.

[0071] The basic immunoglobulin (antibody) structural unit is generally a tetramer. Each tetramer is composed of two identical pairs of polypeptide chains, each pair having one "light" (about 25 kDa) and one "heavy" (about 50-70 kDa) chain. The N-terminus of each chain defines a variable region of about 100 to 110 or more amino acids primarily responsible for antigen recognition. The terms "variable light chain" (V.sub.L) and "variable heavy chain" (V.sub.H) refer, respectively, to these light and heavy chains.

[0072] As used herein, the term "antibodies" includes intact immunoglobulins as well as a number of well-characterized fragments. For instance, Fabs, Fvs, and single-chain Fvs (SCFvs) that bind to target protein (or epitope within a protein or fusion protein) would also be specific binding agents for that protein (or epitope). These antibody fragments are defined as follows: (1) Fab, the fragment which contains a monovalent antigen-binding fragment of an antibody molecule produced by digestion of whole antibody with the enzyme papain to yield an intact light chain and a portion of one heavy chain; (2) Fab', the fragment of an antibody molecule obtained by treating whole antibody with pepsin, followed by reduction, to yield an intact light chain and a portion of the heavy chain; two Fab' fragments are obtained per antibody molecule; (3) (Fab').sub.2, the fragment of the antibody obtained by treating whole antibody with the enzyme pepsin without subsequent reduction; (4) F(ab').sub.2, a dimer of two Fab' fragments held together by two disulfide bonds; (5) Fv, a genetically engineered fragment containing the variable region of the light chain and the variable region of the heavy chain expressed as two chains; and (6) single chain antibody, a genetically engineered molecule containing the variable region of the light chain, the variable region of the heavy chain, linked by a suitable polypeptide linker as a genetically fused single chain molecule. Methods of making these fragments are routine (see, for example, Harlow and Lane, Using Antibodies: A Laboratory Manual, CSHL, New York, 1999).

[0073] BK polyomavirus (BKV): A polyomavirus originally isolated from patient B.K. after renal transplantation (Gardner et al., Lancet 1:1253-1257, 1971). Four BKV serotypes are known (serotypes I-IV; e.g., Knowles et al., J. Med. Virol. 28:118-123, 1989). BKV is nearly ubiquitous, and up to 90% of healthy individuals are seropositive for BKV. Acute infection is generally asymptomatic and proceeds to latent infection, primarily in the urogenital tract. BKV can be reactivated in immunocompromised individuals, and can cause significant morbidity, particularly in renal transplant patients.

[0074] BKV nucleic acid and amino acid sequences are publicly available. For example, GenBank Accession Nos. AB211374, AB263920, AB211386, and AB369093 disclose exemplary BKV-I, BKV-II, BKV-III, and BKV-IV nucleic acid sequences, respectively, all of which are incorporated by reference as present in GenBank on Jul. 15, 2011.

[0075] Capsid polypeptide: One of three structural proteins that forms the polyomavirus capsid. The polyomavirus capsid is formed from viral protein 1 (VP1), viral protein 2 (VP2), and viral protein 3 (VP3).

[0076] Codon-optimized: A "codon-optimized" nucleic acid refers to a nucleic acid sequence that has been altered such that the codons are optimal for expression in a particular system (such as a particular species or group of species). For example, a nucleic acid sequence can be optimized for expression in mammalian cells, bacteria or yeast. Codon optimization does not alter the amino acid sequence of the encoded protein.

[0077] Conservative variants: A substitution of an amino acid residue for another amino acid residue having similar biochemical properties. "Conservative" amino acid substitutions include those substitutions that do not substantially affect or decrease an activity or antigenicity of a polypeptide. A peptide can include one or more amino acid substitutions, for example 1-10 conservative substitutions, 2-5 conservative substitutions, 4-9 conservative substitutions, such as 1, 2, 5 or 10 conservative substitutions. Specific, non-limiting examples of a conservative substitution include the following examples (Table 1).

TABLE-US-00001 TABLE 1 Exemplary conservative amino acid substitutions Original Amino Acid Conservative Substitutions Ala Ser Arg Lys Asn Gln, His Asp Glu Cys Ser Gln Asn Glu Asp His Asn; Gln Ile Leu, Val Leu Ile; Val Lys Arg; Gln; Glu Met Leu; Ile Phe Met; Leu; Tyr Ser Thr Thr Ser Trp Tyr Tyr Trp; Phe Val Ile; Leu

[0078] The term conservative variation also includes the use of a substituted amino acid in place of an unsubstituted parent amino acid, provided that antibodies raised to the substituted polypeptide also immunoreact with the unsubstituted polypeptide, or that an immune response can be generated against the substituted polypeptide that is similar to the immune response against the unsubstituted polypeptide. Thus, in one embodiment, non-conservative substitutions are those that reduce an activity or antigenicity.

[0079] Immune response: A response of a cell of the immune system, such as a B-cell, T-cell, macrophage or polymorphonucleocyte, to a stimulus such as an antigen. An immune response can include any cell of the body involved in a host defense response, for example, an epithelial cell that secretes an interferon or a cytokine. An immune response includes, but is not limited to, an innate immune response or inflammation.

[0080] Immunocompromised: An immunocompromised subject is a subject who is incapable of developing or unlikely to develop a robust immune response, usually as a result of disease, malnutrition, or immunosuppressive therapy. An immunocompromised immune system is an immune system that is functioning below normal Immunocompromised subjects are more susceptible to opportunistic infections, for example viral, fungal, protozoan, or bacterial infections, prion diseases, and certain neoplasms.

[0081] Those who can be considered to be immunocompromised include, but are not limited to, subjects with AIDS (or HIV positive), subjects with severe combined immunodeficiency (SCID), diabetics, subjects who have had transplants and who are taking immunosuppressants, and those who are receiving chemotherapy for cancer. Immunocompromised individuals also includes subjects with most forms of cancer (other than skin cancer), sickle cell anemia, cystic fibrosis, those who do not have a spleen, subjects with end stage kidney disease (dialysis), and those who have been taking corticosteroids or other immune suppressing therapy on a frequent basis within the last year.

[0082] Immunosuppressant: Any compound that decreases the function or activity of one or more aspects of the immune system, such as a component of the humoral or cellular immune system or the complement system. Immunosuppressants are also referred to as "immunosuppressive agents" or "immunosuppressive therapies."

[0083] In some examples, an immunosuppressant includes, but is not limited to: (1) antimetabolites, such as purine synthesis inhibitors (such as inosine monophosphate dehydrogenase (IMPDH) inhibitors, e.g., azathioprine, mycophenolate, and mycophenolate mofetil), pyrimidine synthesis inhibitors (e.g., leflunomide and teriflunomide), and antifolates (e.g., methotrexate); (2) calcineurin inhibitors, such as tacrolimus, cyclosporine A, pimecrolimus, and voclosporin; (3) TNF-.alpha. inhibitors, such as thalidomide and lenalidomide; (4) IL-1 receptor antagonists, such as anakinra; (5) mammalian target of rapamycin (mTOR) inhibitors, such as rapamycin (sirolimus), deforolimus, everolimus, temsirolimus, zotarolimus, and biolimus A9; (6) corticosteroids, such as prednisone; and (7) antibodies to any one of a number of cellular or serum targets (including anti-lymphocyte globulin and anti-thymocyte globulin).

[0084] Exemplary cellular targets and their respective inhibitor compounds include, but are not limited to complement component 5 (e.g., eculizumab); tumor necrosis factors (TNFs) (e.g., infliximab, adalimumab, certolizumab pegol, afelimomab and golimumab); IL-5 (e.g., mepolizumab); IgE (e.g., omalizumab); BAYX (e.g., nerelimomab); interferon (e.g., faralimomab); IL-6 (e.g., elsilimomab); IL-12 and IL-13 (e.g., lebrikizumab and ustekinumab); CD3 (e.g., muromonab-CD3, otelixizumab, teplizumab, visilizumab); CD4 (e.g., clenoliximab, keliximab and zanolimumab); CD11a (e.g., efalizumab); CD18 (e.g., erlizumab); CD20 (e.g., rituximab, afutuzumab, ocrelizumab, pascolizumab); CD23 (e.g., lumiliximab); CD40 (e.g., teneliximab, toralizumab); CD52 (e.g., alemtuzumab); CD62L/L-selectin (e.g., aselizumab); CD80 (e.g., galiximab); CD147/basigin (e.g., gavilimomab); CD154 (e.g., ruplizumab); BLyS (e.g., belimumab); CTLA-4 (e.g., ipilimumab, tremelimumab); CAT (e.g., bertilimumab, lerdelimumab, metelimumab); integrin (e.g., natalizumab); IL-6 receptor (e.g., tocilizumab); LFA-1 (e.g., odulimomab); and IL-2 receptor/CD25 (e.g., basiliximab, daclizumab, inolimomab).

[0085] Inhibiting or treating a disease: "Inhibiting" a disease refers to inhibiting the full development of a disease, for example, PVAN, PML, or BKV-associated hemorrhagic cystitis. Inhibition of a disease can span the spectrum from partial inhibition to substantially complete inhibition (e.g., including, but not limited to prevention) of the disease. In some examples, the term "inhibiting" refers to reducing or delaying the onset or progression of a disease. A subject to be administered with a therapeutically effective amount of the disclosed immunogenic compositions can be identified by standard diagnosing techniques for such a disorder, for example, basis of family history, or risk factor to develop the disease or disorder. "Treatment" refers to a therapeutic intervention that ameliorates a sign or symptom of a disease or pathological condition after it has begun to develop.

[0086] Isolated: An "isolated" or "purified" biological component (such as a nucleic acid, peptide, protein, protein complex, or virus-like particle) has been substantially separated, produced apart from, or purified away from other biological components in the cell of the organism in which the component naturally occurs, that is, other chromosomal and extrachromosomal DNA and RNA, and proteins. Nucleic acids, peptides and proteins that have been "isolated" or "purified" thus include nucleic acids and proteins purified by standard purification methods. The term also embraces nucleic acids, peptides and proteins prepared by recombinant expression in a host cell, as well as chemically synthesized nucleic acids or proteins.

[0087] The term "isolated" or "purified" does not require absolute purity; rather, it is intended as a relative term. Thus, for example, an isolated biological component is one in which the biological component is more enriched than the biological component is in its natural environment within a cell, or other production vessel. Preferably, a preparation is purified such that the biological component represents at least 50%, such as at least 70%, at least 90%, at least 95%, or greater, of the total biological component content of the preparation.

[0088] JC polyomavirus (JCV): A polyomavirus originally isolated from a patient (J.C.) with progressive multifocal leukoencephalopathy (Padgett et al., Lancet 1:1257-1260, 1971). JCV is genetically similar to BKV and simian virus 40 (SV40). JCV is very common in the general population, with 70-90% of individuals seropositive for JCV. The initial site of infection may be the tonsils or gastrointestinal tract. The primary sites of JC infection are thought to be tubular epithelial cells in the kidney, the lining of the ureters and bladder, and oligodendrocytes and astrocytes in the central nervous system.

[0089] JCV can reactivate in immunocompromised individuals and can cause JCV-associated progressive multifocal leukoencephalopathy (PML), which is usually fatal. PML occurs in about 10% of patients suffering from HIV-induced AIDS and can also occur in other immunosuppressed patients, including but not limited to patients treated with rituximab, natalizumab, alemtuzumab, or efalizumab. JCV can also cause urinary tract pathology in some organ transplant recipients.

[0090] JCV nucleic acid and amino acid sequences are publicly available. For example, GenBank Accession Nos. NC_001699, AB038251, and AF281600 disclose exemplary JCV nucleic acid sequences, all of which are incorporated by reference as present in GenBank on Jul. 15, 2011. JCV isolates have been classified into eight distinct genotypes, based in part on the amino acid sequences of VP1 proteins of individual isolates (Cubitt et al., J. Neurovirol. 7:339-344, 2001).

[0091] Pharmaceutically acceptable carrier: The pharmaceutically acceptable carriers (vehicles) useful in this disclosure are conventional. Remington: The Science and Practice of Pharmacy, The University of the Sciences in Philadelphia, Editor, Lippincott, Williams, & Wilkins, Philadelphia, Pa., 21st Edition (2005), describes compositions and formulations suitable for pharmaceutical delivery of one or more therapeutic compositions, such as one or more polyomavirus capsid polypeptides or fragments thereof, and additional pharmaceutical agents.

[0092] In general, the nature of the carrier will depend on the particular mode of administration being employed. For instance, parenteral formulations usually comprise injectable fluids that include pharmaceutically and physiologically acceptable fluids such as water, physiological saline, balanced salt solutions, aqueous dextrose, glycerol or the like as a vehicle. For solid compositions (for example, powder, pill, tablet, or capsule forms), conventional non-toxic solid carriers can include, for example, pharmaceutical grades of mannitol, lactose, starch, or magnesium stearate. In addition to biologically-neutral carriers, pharmaceutical compositions to be administered can contain minor amounts of non-toxic auxiliary substances, such as wetting or emulsifying agents, preservatives, and pH buffering agents and the like, for example sodium acetate or sorbitan monolaurate.

[0093] Polyomavirus: A genus of nonenveloped viruses having an icosahedral capsid. The genome of polyomaviruses includes non-structural proteins (large T-antigen and small t-antigen), a non-coding region including an origin of replication and promoters, and structural proteins (VP1, VP2, and VP3). Polyomaviruses include but are not limited to BK polyomavirus, JC polyomavirus, Merkel cell polyomavirus, and simian virus 40 (SV40). Related human polyomaviruses WU virus (Gaynor et al., PLoS Pathog. 3:e64, 2007) and KI virus (Allander et al., J. Virol. 81:4130-4136, 2007) have recently been reported in clinical samples

[0094] Polyomavirus infection is generally asymptomatic in healthy subjects. However, polyomavirus infection can occur or be reactivated in immunocompromised individuals and can cause significant morbidity. Polyomavirus-associated nephropathy (PVAN; also called BK polyomavirus-associated nephropathy or BK virus nephritis) occurs in up to 10% of renal transplant recipients and is believed to be caused by BKV infection or reactivation of latent BKV infection. It causes kidney allograft dysfunction and may lead to loss of the allograft. Polyomavirus-associated hemorrhagic cystitis is characterized by inflammation of the bladder leading to dysuria, hematuria, and hemorrhage. It can occur in bone marrow transplant recipients and other individuals who are receiving immunosuppressants or other therapies which decrease immune system function.

[0095] Sequence identity: The similarity between two nucleic acid sequences, or two amino acid sequences, is expressed in terms of the similarity between the sequences, otherwise referred to as sequence identity. Sequence identity is frequently measured in terms of percentage identity (or similarity or homology); the higher the percentage, the more similar the two sequences are.

[0096] Methods of alignment of sequences for comparison are well known in the art. Various programs and alignment algorithms are described in: Smith & Waterman, Adv. Appl. Math. 2: 482, 1981; Needleman & Wunsch, J. Mol. Biol. 48: 443, 1970; Pearson & Lipman, Proc. Natl. Acad. Sci. USA 85: 2444, 1988; Higgins & Sharp, Gene, 73: 237-244, 1988; Higgins & Sharp, Comput. Appl. Biosci. 5: 151-153, 1989; Corpet et al., Nucl. Acids Res. 16, 10881-90, 1988; Huang et al., Comput. Appl. Biosci. 8, 155-65, 1992; and Pearson, Methods Mol. Biol. 24:307-331, 1994. Altschul et al. (J. Mol. Biol. 215:403-410, 1990) presents a detailed consideration of sequence alignment methods and homology calculations.

[0097] The NCBI Basic Local Alignment Search Tool (BLAST) (Altschul et al., J. Mol. Biol. 215:403-410, 1990) is available from several sources, including the National Center for Biotechnology Information (NCBI, Bethesda, Md.) and on the Internet, for use in connection with the sequence analysis programs blastp, blastn, blastx, tblastn and tblastx. By way of example, for comparisons of amino acid sequences of greater than about 30 amino acids, the Blast 2 sequences function is employed using the default BLOSUM62 matrix set to default parameters (gap existence cost of 11, and a per residue gap cost of 1). When aligning short peptides (fewer than around 30 amino acids), the alignment is performed using the Blast 2 sequences function, employing the PAM30 matrix set to default parameters (open gap 9, extension gap 1 penalties).

[0098] Nucleic acid sequences that do not show a high degree of sequence identity may nevertheless encode similar amino acid sequences, due to the degeneracy of the genetic code. It is understood that changes in nucleic acid sequence can be made using this degeneracy to produce multiple nucleic acid molecules that all encode substantially the same protein.

[0099] Subject: Living multi-cellular vertebrate organisms, a category that includes both human and non-human mammals (such as mice, rats, rabbits, sheep, horses, cows, and non-human primates).

[0100] Therapeutically effective amount: A quantity of a specified agent sufficient to achieve a desired effect in a subject being treated with that agent. For example, this may be the amount of a polyomavirus capsid polypeptide or nucleic acid (or fragment thereof) useful for eliciting an immune response in a subject and/or for inhibiting or preventing infection or pathology by a polyomavirus (such as BKV or JCV). Ideally, in the context of the present disclosure, a therapeutically effective amount of a polyomavirus polypeptide or nucleic acid (or fragment thereof) is an amount sufficient to increase resistance to, prevent, ameliorate, and/or treat infection caused by a polyomavirus in a subject without causing a substantial cytotoxic effect in the subject. The effective amount of a polyomavirus polypeptide or nucleic acid (or fragment thereof) useful for increasing resistance to, preventing, ameliorating, and/or treating infection in a subject will be dependent on, for example, the subject being treated, the manner of administration of the therapeutic composition, and other factors.

[0101] Virus-like particle (VLP): A non-replicating viral shell, derived from any of several viruses. VLPs are generally composed of one or more viral proteins, such as, but not limited to, those proteins referred to as capsid, coat, shell, surface and/or envelope proteins, or particle-forming polypeptides derived from these proteins. VLPs can form spontaneously upon recombinant expression of the protein in an appropriate expression system. Methods for producing particular VLPs are known in the art. The presence of VLPs following recombinant expression of viral proteins can be detected using conventional techniques known in the art, such as by electron microscopy, biophysical characterization, and the like. See, for example, Baker et al. (1991) Biophys. J. 60:1445-1456; Hagensee et al. (1994) J. Virol. 68:4503-4505. For example, VLPs can be isolated by density gradient centrifugation and/or identified by characteristic density banding. Alternatively, cryoelectron microscopy can be performed on vitrified aqueous samples of the VLP preparation in question, and images recorded under appropriate exposure conditions.

III. Immune Response to Polyomavirus

[0102] Disclosed herein are methods of eliciting an immune response against a polyomavirus (for example, BKV or JCV). The disclosed methods utilize one or more capsid polypeptides (or a fragment thereof) of a polyomavirus to elicit an immune response in a subject. In some examples, the methods are of use to treat, inhibit, or even prevent infection of a subject with a polyomavirus or to treat, inhibit, or even prevent polyomavirus-associated disorders (for example, PVAN, BKV-associated hemorrhagic cystitis, and/or JCV-associated PML). In some embodiments, the methods include administering at least one capsid polypeptide (or a fragment thereof) from each of two or more BKV serotypes (such as a multivalent BKV serotype immunogenic composition) to a subject. In some embodiments, the multivalent immunogenic composition includes at least one capsid polypeptide (or a fragment thereof) from two or more BKV-I subtypes (such as BKV-Ia, BKV-Ib1, BKV-Ib2, and/or BKV-Ic subtypes). In additional embodiments, the methods further include administering at least one JCV capsid polypeptide (or a fragment thereof) to the subject. Also disclosed are methods of identifying a transplant donor and/or transplant recipient (such as a renal transplant donor or recipient) who does not have antibodies for one or more BKV serotypes (for example, BKV-IV or BKV-I), such as a donor and/or recipient who does not have detectable levels of antibodies capable of neutralizing one or more BKV serotypes (for example, BKV-I or BKV-IV).

[0103] A. Methods of Eliciting an Immune Response to BKV

[0104] In some embodiments, the methods include eliciting an immune response against a BKV in a subject (such as one or more BKV serotypes). The methods include administering to a subject in need of enhanced immunity to BKV a therapeutically effective amount of at least one isolated BKV-I capsid polypeptide (or a fragment thereof) or a nucleic acid encoding the at least one BKV-I capsid polypeptide (such as at least one BKV-Ia VP1 polypeptide, BKV-Ib1 VP1 polypeptide, BKV-Ib2 VP1 polypeptide, and/or BKV-Ic VP1 polypeptide) and a therapeutically effective amount of at least one isolated BKV-IV capsid polypeptide (or a fragment thereof) or a nucleic acid encoding the at least one BKV-IV capsid polypeptide (such as at least one BKV-IVb1 VP1 polypeptide and/or BKV-IVc2 VP1 polypeptide). In some examples, the at least one BKV-I capsid polypeptide (or fragment thereof) and the at least one BKV-IV capsid polypeptide (or fragment thereof) are different from one another. The BKV-I and BKV-IV capsid polypeptides include one or more of VP1, VP2, and VP3 (such as SEQ ID NOs: 1-6 and 13-16), and are discussed in detail in Section IV, below. In particular examples, administering the at least one isolated BKV-I capsid polypeptide includes administering a VLP including the BKV-I capsid polypeptide(s) and/or administering the at least one BKV-IV capsid polypeptide includes administering a VLP including the BKV-IV capsid polypeptide(s). In particular examples, the subject does not have BKV-IV neutralizing antibodies. In other examples, the subject does not have BKV-I neutralizing antibodies.

[0105] In one non-limiting example, the methods include administering to a subject in need of enhanced immunity to BKV a therapeutically effective amount of at least one BKV-Ia VP1 polypeptide, at least one BKV-Ib2 VP1 polypeptide, and at least one BKV-IV VP1 polypeptide (such as at least one BKV-IVb1 VP1 polypeptide and/or BKV-IVc2 VP1 polypeptide). In other examples, the methods may also include administering to a subject in need of enhanced immunity to BKV a therapeutically effective amount of at least one BKV-Ic VP1 polypeptide. In some examples, the BKV-Ia/Ib1 VP1 polypeptide includes a glutamic acid at amino acid position 73 and/or a glutamic acid at amino acid position 82 (such as SEQ ID NO: 1 or SEQ ID NO: 13). In additional examples, the BKV-Ib2 VP1 polypeptide includes a lysine residue at amino acid position 73 and/or an aspartic acid at amino acid position 82 (such as SEQ ID NO: 14).

[0106] In some examples, the methods further include administering to the subject a therapeutically effective amount of at least one isolated BKV-II capsid polypeptide (or a fragment thereof) or a nucleic acid encoding the at least one BKV-II capsid polypeptide and/or a therapeutically effective amount of at least one BKV-III capsid polypeptide (or a fragment thereof) or a nucleic acid encoding the at least one BKV-III capsid polypeptide. In some examples, the BKV-II capsid polypeptide (or fragment thereof) and the BKV-III capsid polypeptide (or fragment thereof) are different from one another and are also different from the BKV-I and BKV-IV capsid polypeptides (or fragments thereof). The BKV-II and BKV-III capsid polypeptides include one or more of VP1, VP2, and VP3 (such as SEQ ID NOs: 7-12), and are discussed in detail in Section IV, below. In particular examples, administering the at least one isolated BKV-II capsid polypeptide includes administering a VLP including the BKV-II capsid polypeptide(s) and/or administering the at least one BKV-III capsid polypeptide includes administering a VLP including the BKV-III capsid polypeptide(s).

[0107] In some embodiments, the methods further include selecting a subject in need of enhanced immunity to BKV. In some examples, a subject in need of enhanced immunity to BKV is a subject at risk of BKV infection or at risk of BKV-associated disorders, such as PVAN or BKV-associated hemorrhagic cystitis. Subjects in need of enhanced immunity to BKV include subjects who are immunocompromised, for example subjects who are infected with human immunodeficiency virus (HIV), subjects with SCID, diabetics, subjects who are receiving chemotherapy for cancer, and subjects who are receiving immunosuppressive therapy (such as corticosteroids, a calcineurin inhibitor, such as tacrolimus, cyclosporine, or pimecrolimus, or other therapies that decrease immune system function, such as rituximab, natalizumab, efalizumab, or alemtuzumab). In some examples, subjects who are receiving immunosuppressive therapy include individuals who have received an organ transplant (such as a renal transplant or other solid organ transplant or a bone marrow transplant). In a particular example, a subject in need of enhanced immunity to BKV is a renal transplant recipient. In another example, a subject in need of enhanced immunity to BKV is a bone marrow transplant recipient. In other examples, subjects in need of enhanced immunity to BKV include those who are candidates for organ or bone marrow transplantation or those who are candidates for immunosuppressive therapy. In a particular example, the subject has renal failure or is otherwise a candidate for a renal transplant. In further examples, a subject in need of enhanced immunity to BKV may include a subject who has or is at risk for cancer (for example, prostate cancer or bladder carcinoma).

[0108] In additional embodiments, the methods further include administering to the subject a therapeutically effective amount of at least one JCV capsid polypeptide (or a fragment thereof) or a nucleic acid encoding the at least one JCV capsid polypeptide. The JCV capsid polypeptides include one or more of VP1, VP2, and VP3 (for example, SEQ ID NOs: 17-23), and are discussed in detail in Section IV, below. In particular examples, administering the at least one isolated JCV capsid polypeptide includes administering a VLP including the JCV capsid polypeptide(s).

[0109] In some examples, the subject who is administered the at least one JCV capsid polypeptide or nucleic acid encoding the JCV capsid polypeptide is a subject in need of enhanced immunity to JCV or a subject at risk of a JCV-associated disorder (for example, JCV-associated PML). In particular examples, the subject is an immunocompromised subject, for example a subject who is infected with HIV, a subject with SCID, a diabetic subject, a subject who is receiving chemotherapy for cancer, or a subject who is receiving immunosuppressive therapy (such as corticosteroids, a calcineurin inhibitor, such as tacrolimus, cyclosporine, or pimecrolimus, or other therapies that decrease immune system function, such as rituximab, natalizumab, efalizumab, or alemtuzumab). In some examples, a subject who is receiving immunosuppressive therapy includes a subject who has received an organ transplant (such as a renal transplant or other solid organ transplant or a bone marrow transplant). In a particular example, a subject in need of enhanced immunity to JCV is a renal transplant recipient or a bone marrow transplant recipient. In another example, a subject in need of enhanced immunity to JCV is a subject who is receiving rituximab therapy (or a subject who will or has received rituximab therapy). In other examples, subjects in need of enhanced immunity to JCV include those who are candidates for organ or bone marrow transplantation or those who are candidates for immunosuppressive therapy.

[0110] B. Methods of Treating or Inhibiting Polyomavirus-Associated Disorders

[0111] In some embodiments, the methods include treating or inhibiting (or in some examples, even preventing) a polyomavirus-associated disorder, such as PVAN, BKV-associated hemorrhagic cystitis, or JCV-associated PML. In some examples, the methods include administering to a subject in need of treatment for or inhibition of a polyomavirus-associated disorder a therapeutically effective amount of at least one isolated BKV-IV capsid polypeptide (or a fragment thereof) or a nucleic acid encoding the at least one BKV-IV capsid polypeptide to the selected subject (such as at least one BKV-IVb1 VP1 polypeptide and/or at least one BKV-IVc2 VP1 polypeptide). In some examples, administering the one or more BKV-IV capsid polypeptides (such as VP1, VP2, or VP3, for example, SEQ ID NOs: 4-6 and/or SEQ ID NO: 16) includes administering a VLP including the capsid polypeptide(s).

[0112] In some embodiments, the methods further include selecting a subject in need of treatment for inhibition of a polyomavirus-associated disorder. In some examples, a subject is need of treating or inhibiting PVAN or BK-associated hemorrhagic cystitis. (such as a subject who has had an organ or bone marrow transplant or a candidate for an organ or bone marrow transplant). In one example, the subject is a candidate for a kidney transplant. In other examples, the subject is a candidate for a bone marrow transplant. In further examples, the subject is immunocompromised (such as a transplant recipient, a subject who is infected with HIV, or a subject treated with an immunosuppressant), or is a candidate for treatment with an immunosuppressant (such as an organ or bone marrow transplant candidate). In particular examples, the subject does not have BKV-IV neutralizing antibodies and/or BKV-I neutralizing antibodies.

[0113] In some examples, the methods further include administering to the subject a therapeutically effective amount of at least one isolated BKV-I capsid polypeptide (or a fragment thereof) or a nucleic acid encoding the at least one BKV-I capsid polypeptide, at least one isolated BKV-II capsid polypeptide (or a fragment thereof) or a nucleic acid encoding the at least one BKV-II capsid polypeptide, at least one isolated BKV-III capsid polypeptide (or a fragment thereof) or a nucleic acid encoding the at least one BKV-III capsid polypeptide, at least one isolated JCV capsid polypeptide (or a fragment thereof) or a nucleic acid encoding the at least one JCV capsid polypeptide, or a combination of two or more thereof (for example, one or more of SEQ ID NOs: 1-23). In particular non-limiting examples, the methods include administering to the subject a therapeutically effective amount of at least one BKV-Ia VP1 polypeptide and at least one BKV-Ib2 VP1 polypeptide (such as SEQ ID NOs: 1, 14, or 15). In some examples, administering the one or more BKV and/or JCV capsid polypeptides (such as VP1, VP2, or VP3) includes administering a VLP including the capsid polypeptide(s).

[0114] In particular examples, the subject is a candidate for organ transplant (for example, renal transplant or bone marrow transplant) and the therapeutically effective amount of the BKV-IV capsid polypeptide or nucleic acid encoding the capsid polypeptide is administered to the subject a sufficient time prior to the organ transplant to produce an immune response to the BKV-IV capsid polypeptide in the subject. One of skill in the art can identify the time required to produce an immune response in the subject based on factors such as the general state of the subject's health, and the robustness of the subject's immune system. In some examples, the at least one isolated BKV-IV capsid polypeptide or nucleic acid encoding the BKV-IV capsid polypeptide is administered to the subject at least about six months (for example, at least about 6 months, 5 months, 4 months, 3 months, 2 months, 6 weeks, 5 weeks, 4 weeks, 3 weeks, 2 weeks, or even 1 week) prior to the organ transplant. In some examples, the BKV-IV capsid polypeptide is administered to the subject at least about 2 weeks prior to the organ transplant. In other examples, the BKV-IV capsid polypeptide is administered to the subject at least about 6 weeks prior to the organ transplant, with a booster dose about 2 weeks prior to transplant. In some examples, a BKV-I, BKV-II, BKV-III, and/or JCV capsid polypeptide (or fragment thereof) is further administered to the subject prior to the organ transplant.

[0115] In additional embodiments, the methods include administering to the subject a therapeutically effective amount of a purified human gamma globulin preparation that has been found to contain antibodies capable of neutralizing BKV-I, BKV-II, BKV-III and/or BKV-IV. Subjects include those described above. Methods of identifying serum containing BKV-I, BKV-II, BKV-III, and/or BKV-IV neutralizing antibodies are known to one of skill in the art and include the methods discussed in Section VI, below. In some examples, the gamma globulin preparations that may be used include commercially available preparations of intact gamma globulin and preparations of the Fc, F(ab') 2 fragments of gamma globulin or combinations thereof. Methods of preparing gamma globulin, for example, for administration to a subject are known to one of ordinary skill in the art. See, e.g., U.S. Pat. Nos. 5,177,194; 6,504,012; and 7,879,331.

[0116] The dosage of gamma globulin and the method of administration will vary with the severity and nature of the particular condition being treated, the duration of treatment, the adjunct therapy used, the age and physical condition of the subject of treatment and similar factors. In some examples, dosages for intravenous administration are from 100 mg/kg to 2.5 g/kg (such as about 400 mg/kg to 2 g/kg or 1 g/kg to 2 g/kg). The dosage can be varied based on the frequency of administration, for example, 400 mg/kg/day for 5 consecutive days per month or 2 g/kg/day once a month. In another example, the gamma globulin preparation is administered subcutaneously or intramuscularly. In some examples, the dosage for subcutaneous or intramuscular administration is from about 1 mg/kg to 30 mg/kg body weight (such as about 4 mg/kg to 20 mg/kg or about 10 mg/kg to 20 mg/kg). The gamma globulin is administered as a pharmaceutical composition containing a pharmaceutically acceptable carrier. Pharmaceutically acceptable carriers of use for gamma globulin compositions include those described in section V, below.

[0117] C. Methods of Selecting a Renal Transplant Donor and/or Recipient

[0118] In further embodiments, the methods include selecting a candidate organ transplant donor and/or organ transplant recipient. In some examples, the candidate donor is a candidate renal transplant donor and the candidate transplant recipient is a candidate renal transplant recipient. The methods include screening a candidate donor and/or recipient for presence of BKV serotype-specific antibodies (including, but not limited to BKV-IV-specific neutralizing antibodies).

[0119] In some embodiments, the methods include selecting a subject as a renal transplant donor if BKV serotype-specific (such as BKV-IV or BKV-I) neutralizing antibodies are not present in the subject. In some examples, the methods further include selecting a subject as a renal transplant recipient if BKV serotype-specific (such as BKV-IV or BKV-I) neutralizing antibodies are not present in the subject who is a candidate transplant recipient. In some examples, the methods include detecting presence of BKV-IV neutralizing antibodies in a subject (for example, in a sample from a subject) and selecting the subject as a transplant donor or recipient if BKV-IV neutralizing antibodies are not present in the sample. The sample can include any suitable biological sample from the subject, including a blood sample or serum sample.

[0120] Methods of detecting neutralizing antibodies in a subject (such as in a blood or serum sample from a subject) are known to one of ordinary skill in the art. Such methods are discussed in Section VI, below.

[0121] IV. Polyomavirus Capsid Polypeptides

[0122] Polyomavirus nucleic acid and polypeptide sequences are publicly available and can be identified by one of skill in the art. Exemplary BKV genomic nucleic acid sequences include, but are not limited to, GenBank Accession Nos. JF894228, AB211374, DQ989796, AB211377, AB263920, AB211386, AB211390, and AB369093, each of which is incorporated herein by reference as present in GenBank on Jul. 15, 2011.

[0123] It is disclosed herein that several BKV capsid polypeptides (or fragments thereof) can be used to elicit an immune response to BKV. In several embodiments, the BKV capsid polypeptide comprises or consists of the amino acid sequence set forth as SEQ ID NOs: 1-12. Additional BKV VP1 polypeptides are disclosed herein, for example from additional BKV subtypes. In some embodiments, the BKV VP1 polypeptide comprises or consists of the amino acid sequence set forth as SEQ ID NOs: 13-16.

[0124] Exemplary JCV genomic nucleic acid sequences include, but are not limited to, GenBank Accession Nos. NC_001699, AF300945, and AY536541, each of which is incorporated herein by reference as present in GenBank on Jul. 15, 2011.

[0125] It is also disclosed herein that several JCV capsid polypeptides (or fragments thereof) can be used to elicit an immune response to JCV, for example, in combination with one or more BKV capsid polypeptides. In several embodiments, the JCV capsid polypeptide comprises or consists of the amino acid sequence set forth as SEQ ID NOs: 17-23.

[0126] In some embodiments, the polyomavirus capsid polypeptides (such as BKV or JCV capsid polypeptides) of use in the methods disclosed herein have a sequence at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%, such as 100% identical to the amino acid sequence set forth in one of SEQ ID NOs: 1-23 or 52-125. In other examples, the polyomavirus capsid polypeptides (such as BKV VP1 polypeptides) comprise a sequence at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%, such as 100% identical to the amino acid sequence set forth in one of SEQ ID NOs: 126-158. In some examples, the BKV subtype or serotype of the polypeptide is known. In other examples, the BKV subtype or serotype of the polypeptide is not known. One of ordinary skill in the art can determine the BKV subtype or serotype of an unknown BKV capsid polypeptide, for example by sequence analysis and ELISA or neutralizing assays (such as those described in Examples 1-3, below). Exemplary sequences can be obtained using computer programs that are readily available on the internet and the amino acid sequences set forth herein. In one example, the polypeptide retains a function of the polyomavirus capsid polypeptide, such as binding to an antibody that specifically binds the polyomavirus epitope.

[0127] Minor modifications of a polyomavirus capsid polypeptide primary amino acid sequences may result in peptides which have substantially equivalent activity as compared to the unmodified counterpart polypeptide described herein. Such modifications may be deliberate, as by site-directed mutagenesis, or may be spontaneous. All of the polypeptides produced by these modifications are included herein. Thus, a specific, non-limiting example of a polyomavirus capsid polypeptide is a conservative variant of the polyomavirus capsid polypeptide (such as a single conservative amino acid substitution, for example, one or more conservative amino acid substitutions, for example 1-10 conservative substitutions, 2-5 conservative substitutions, 4-9 conservative substitutions, such as 1, 2, 5 or 10 conservative substitutions). A table of conservative substitutions is provided herein. Substitutions of the amino acids sequence shown in SEQ ID NOs: 1-23 or 52-158 can be made based on this table.

[0128] An "epitope" or "antigenic determinant" refers to a site on an antigen to which B and/or T cells respond. T cells can respond to the epitope when the epitope is presented in conjunction with an MHC molecule. Epitopes can be formed both from contiguous amino acids (linear) or noncontiguous amino acids juxtaposed by tertiary folding of an antigenic polypeptide (conformational). Epitopes formed from contiguous amino acids are typically retained on exposure to denaturing solvents whereas epitopes formed by tertiary folding are typically lost on treatment with denaturing solvents. Normally, a B-cell epitope will include at least about 5 amino acids but can be as small as 3-4 amino acids. A T-cell epitope, such as a CTL epitope, will include at least about 7-9 amino acids, and a helper T-cell epitope at least about 12-20 amino acids. Normally, an epitope will include between about 5 and 15 amino acids, such as 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15 amino acids. In some examples, the immunogenic compositions disclosed herein include a fragment (such as an immunogenic fragment) or antigenic determinant of a polyomavirus capsid protein. One of skill in the art can identify predicted antigenic determinants, for example using an HLA peptide binding prediction program, such as BIMAS (www-bimas.cit.nih.gov/molbio/hla_bind/) or IEDB analysis resource (immuneeptiope.org). In some examples, the polyomavirus capsid polypeptide includes, consists essentially of, or consists of five or more amino acids (for example, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, or 23 amino acids) of the VP1 BC loop (e.g., amino acids 61-83 of a BKV VP1 polypeptide; see, e.g., Tremolada et al., Virus Res. 149:190-196, 2010).

[0129] The polyomavirus capsid polypeptides disclosed herein can be chemically synthesized by standard methods, or can be produced recombinantly. An exemplary process for polypeptide production is described in Lu et al., FEBS Lett. 429:31-35, 1998. They can also be isolated by methods including preparative chromatography and immunological separations. Polypeptides can also be produced using molecular genetic techniques, such as by inserting a nucleic acid encoding at least one polyomavirus capsid polypeptide or an epitope thereof into an expression vector, introducing the expression vector into a host cell, and isolating the polypeptide. Any suitable cell can be utilized to express the disclosed polypeptides, including bacteria (e.g., E. coli), yeast, insect cells (e.g., Sf9 cells), or mammalian cells (e.g., 293 cells). In some examples, the polypeptide spontaneously assembles into a virus-like particle (VLP).

[0130] In some examples, the disclosed polyomavirus capsid polypeptides (or fragments thereof), for example a capsid polypeptide comprising the amino acid sequence of one or more of SEQ ID NOs: 1-23 or 52-125, are a part of a VLP, such as a BKV-I VLP, BKV-II VLP, BKV-III VLP, BKV-IV VLP, or JCV VLP. Immunogens are typically presented multimerically (e.g., about 72 pentamers or about 360 capsid polypeptides per VLP particle) to immune cells such as B cells and antigen presenting cells. This results in effectively inducing immune responses against the immunogen, in particular, antibody responses. In some examples, the VLP includes one or more of VP1, VP2, and VP3 (such as 1, 2, or all 3) from BKV-I (such as BKV-Ia, BKV-Ib1, BKV-Ib2, and/or BKV-Ic), BKV-II, BKV-III, BKV-IV (such as BKV-IVb1 and/or BKV-IVc2), or JCV.

[0131] In specific embodiments, the antigen that is part of the disclosed VLPs includes one or more of the amino acid sequences set forth as SEQ ID NOs: 1-23 or 52-158 (or fragments thereof) and have the ability to spontaneously assemble into VLPs. In some examples, a VLP includes a BKV-I VP1 polypeptide (such as one of SEQ ID NOs: 1, 13, 14, or 15) and a BKV-I VP2 polypeptide (such as SEQ ID NO: 2) and/or BKV-I VP3 polypeptide (such as SEQ ID NO: 3). In other examples, a VLP includes a BKV-I VP1 polypeptide (such as one of SEQ ID NOs: 1, 13, 14, or 15) and a BKV-IV VP2 polypeptide (such as SEQ ID NO: 5) and/or BKV-IV VP3 polypeptide (such as SEQ ID NO: 6). In other examples, a VLP includes a BKV-II VP1 polypeptide (such as SEQ ID NO: 7) and a BKV-II VP2 polypeptide (such as SEQ ID NO: 8) and/or BKV-II VP3 polypeptide (such as SEQ ID NO: 9). In other examples, a VLP includes a BKV-II VP1 polypeptide (such as SEQ ID NO: 7) and a BKV-IV VP2 polypeptide (such as SEQ ID NO: 5) and/or BKV-IV VP3 polypeptide (such as SEQ ID NO: 6). In additional examples, a VLP includes a BKV-III VP1 polypeptide (such as SEQ ID NO: 10) and a BKV-III VP2 polypeptide (such as SEQ ID NO: 11) and/or BKV-III VP3 polypeptide (such as SEQ ID NO: 12). In other examples, a VLP includes a BKV-III VP1 polypeptide (such as SEQ ID NO: 10) and a BKV-IV VP2 polypeptide (such as SEQ ID NO: 5) and/or BKV-IV VP3 polypeptide (such as SEQ ID NO: 6). In still further examples, a VLP includes a BKV-IV VP1 polypeptide (such as one of SEQ ID NOs: 4 and 16) and a BKV-IV VP2 polypeptide (such as SEQ ID NO: 5) and/or BKV-IV VP3 polypeptide (such as SEQ ID NO: 6). In another example, a VLP includes a JCV VP1 polypeptide (such as one of SEQ ID NOs: 17, 20, or 21) and a JCV VP2 polypeptide (such as SEQ ID NO: 22) and/or JCV VP3 polypeptide (such as SEQ ID NO: 23).

[0132] In further examples, a fragment of a disclosed polyomavirus capsid polypeptide retains the ability to spontaneously assemble into VLPs. Fragments (such as immunogenic fragments) and variants can be of varying length. For example, a fragment may consist of six or more, 25 or more, 50 or more, 75 or more, 100 or more, or 200 or more amino acid residues of a polyomavirus capsid amino acid sequence. This includes, for example, any polypeptide six or more amino acid residues in length that is capable of spontaneously assembling into VLPs. Methods to assay for VLP formation and isolation of VLPs are well known in the art (see, for example, Pastrana et al., PLoS Pathogens 5(9):e1000578, 2009, herein incorporated by reference in its entirety).

[0133] Polynucleotides encoding the BKV capsid polypeptides disclosed herein are also provided. Exemplary nucleic acid sequences are set forth as SEQ ID NOs: 24-35. Polynucleotides encoding the JCV capsid polypeptides disclosed herein are also provided. Exemplary nucleic acid sequences are set forth as SEQ ID NOs: 36-38.

[0134] In some embodiments, the nucleic acids encoding the BKV capsid polypeptides are codon-optimized for expression in a heterologous system (such as mammalian cells, bacteria or yeast). Exemplary nucleic acid sequences codon-optimized for mammalian cells are set forth as SEQ ID NOs: 39-51 (although the codon-optimized sequences can still be expressed in other systems, such as bacteria).

[0135] In some embodiments, the nucleic acid sequences encoding polyomavirus capsid polypeptides (such as BKV or JCV capsid polypeptides) of use in the methods disclosed herein have a sequence at least 85%, 90%, 95%, 96%, 97%, 98%, or 99%, such as 100% identical to the nucleic acid sequence set forth in one of SEQ ID NOs: 24-51. Exemplary sequences can be obtained using computer programs that are readily available on the internet and the nucleic acid sequences set forth herein. In one example, the polypeptide encoded by the nucleic acid sequence retains a function of the polyomavirus capsid polypeptide, such as binding to an antibody that specifically binds the polyomavirus epitope.

[0136] V. Pharmaceutical Compositions and Modes of Administration

[0137] The polyomavirus capsid polypeptides (or fragments thereof) disclosed herein, or nucleic acids encoding the polyomavirus capsid polypeptides, can be used to elicit an immune response in a subject. In several examples, the subject is infected with at least one BKV serotype or is at risk of being infected with a BKV serotype (such as one or more of BKV-I, BKV-II, BKV-III, or BKV-IV) and/or JCV. Thus, in several embodiments, the methods include administering to a subject a therapeutically effective amount of one or more of the polyomavirus capsid polypeptides (or fragments thereof) disclosed herein (or polynucleotides encoding these polypeptides) in order to elicit an immune response, such as, but not limited to, a protective immune response.

[0138] In the disclosed methods, compositions are administered to a subject in an amount sufficient to produce an immune response to a polyomavirus (for example, BKV). The disclosed BKV polypeptides, VLPs including the BKV polypeptides, or polynucleotides encoding these polypeptides, are of use to inhibit (or even prevent) an infection with BKV in a subject, inhibit (or even prevent) progression to disease in a subject having a latent BKV infection, or to inhibit or treat BKV-associated disorders (for example, PVAN or BKV-associated hemorrhagic cystitis) in a subject infected with BKV. In several examples, administration of a therapeutically effective amount of a composition including one or more BKV serotype-specific capsid polypeptides (or fragments thereof) disclosed herein (or polynucleotides encoding these polypeptides) induces a sufficient immune response to decrease a symptom of a disease due to BKV infection, to inhibit the development of one or more symptoms of BKV or a BKV-associated disorder, or to inhibit infection with BKV (such as a BKV serotype, for example, BKV-I, BKV-II, BKV-III, and/or BKV-IV).

[0139] In some examples, the compositions are of use in inhibiting or even preventing a future infection with BKV. Thus, in some examples, a therapeutically effective amount of the composition is administered to a subject at risk of becoming infected with BKV (for example, an immunocompromised subject or a subject who has received or is a candidate for an organ transplant). The composition inhibits the development of BKV, such as latent or active BKV infection, in the subject upon subsequent exposure to BKV, or loss of immunological control over an existing BKV infection (for example reactivation of a latent infection).

[0140] In some embodiments, the methods further include administering to a subject a therapeutically effective amount of one or more of the JCV capsid polypeptides (or fragment thereof) disclosed herein (or polynucleotides encoding these polypeptides) in order to elicit an immune response, such as, but not limited to, a protective immune response against JCV. In some examples, the compositions are of use in inhibiting or even preventing a future infection with JCV. Thus, in some examples, a therapeutically effective amount of the composition is administered to a subject at risk of becoming infected with JCV (for example, an immunocompromised subject or a subject who has or is a candidate for organ transplantation). The composition inhibits or prevents the development of JCV, such as latent or active JCV infection, in the subject upon subsequent exposure to JCV, or loss of immunological control over an existing JCV infection (for example reactivation of a latent infection). In some examples, the disclosed methods and compositions inhibit or treat JCV-associated disorders (for example, JCV-associated PML) in a subject infected with JCV. In particular examples, the subject is at risk of developing JCV-associated PML, such as a subject infected with HIV, a subject on immune-suppressing therapy (for example, mycophenolate, fludarabine, methotrexate, rituximab, natalizumab, alemtuzumab, or efalizumab), or a subject who has, or is a candidate for, organ transplantation (such as a bone marrow transplant).

[0141] Amounts effective for these uses will depend upon the severity of the disease, the general state of the subject's health, and the robustness of the subject's immune system. In one example, a therapeutically effective amount of the compound is that which provides either subjective relief of a symptom or an objectively identifiable improvement as noted by the clinician or other qualified observer. In other examples, a therapeutically effective amount is an amount sufficient to inhibit an infection with BKV (such as BKV-I, BKV-II, BKV-III, and/or BKV-IV) in a subject upon subsequent exposure of the subject to one or more BKV serotypes. In additional examples, a therapeutically effective amount is an amount sufficient to inhibit development of one or more symptoms in a subject infected with BKV (for example, PVAN or BKV-associated hemorrhagic cystitis).

[0142] In further examples, a therapeutically effective amount is an amount sufficient to inhibit an infection with JCV in a subject upon subsequent exposure of the subject to one or more JCV serotypes or inhibit the emergence of an existing JCV infection from asymptomatic latency in a subject. In additional examples, a therapeutically effective amount is an amount sufficient to inhibit development of one or more symptoms in a subject infected with JCV (for example, JCV-associated PML).

[0143] In some examples, one or more polyomavirus capsid polypeptides (such as BKV or JCV capsid polypeptides) or fragments thereof described herein may be covalently linked to at least one other immunogenic protein, wherein the conjugate elicits an immune response to the polyomavirus capsid polypeptide in a subject. The other immunogenic protein (sometimes referred to as a "carrier" protein) ideally has the properties of being immunogenic by itself, usable in a subject, and of a size that can be easily purified and conjugated to at least one other protein or peptide. Suitable carrier proteins are known to one of skill in the art. In particular examples, the other immunogenic protein (carrier protein) is bovine serum albumin (BSA), ovalbumin, tetanus toxoid, diphtheria toxoid, cholera toxin, Clostridium difficile toxin A, C. difficile toxin B, Shiga toxin, or Pseudomonas aeruginosa recombinant exoprotein A.

[0144] A polyomavirus capsid polypeptide can be administered by any means known to one of skill in the art (see Banga, A., "Parenteral Controlled Delivery of Therapeutic Peptides and Proteins," in Therapeutic Peptides and Proteins, Technomic Publishing Co., Inc., Lancaster, Pa., 1995) either locally or systemically, such as by intramuscular injection, subcutaneous injection, intraperitoneal injection, intravenous injection, oral administration, nasal administration, transdermal administration, or even anal administration. In some embodiments, administration is by oral administration, subcutaneous injection, or intramuscular injection.

[0145] In one specific, non-limiting example, the polyomavirus capsid polypeptide is administered in a manner to direct the immune response to a cellular response (that is, a helper T cell or cytotoxic T lymphocyte (CTL) response), rather than a humoral (antibody) response.

[0146] To extend the time during which the peptide or protein is available to stimulate a response, the peptide or protein can be provided as an implant, an oily injection, or as a particulate system. The particulate system can be a microparticle, a microcapsule, a microsphere, a nanocapsule, or similar particle. (see, e.g., Banga, supra). A particulate carrier based on a synthetic polymer has been shown to act as an adjuvant to enhance the immune response, in addition to providing a controlled release. Aluminum salts can also be used as adjuvants to produce an immune response.

[0147] Optionally, one or more cytokines, such as IL-2, IL-6, IL-12, RANTES, GM-CSF, TNF-.alpha., or IFN-.gamma., one or more growth factors, such as GM-CSF or G-CSF; one or more molecules such as OX-40L or 4-1 BBL, or combinations of these molecules, can be used as biological adjuvants (see, for example, Salgaller et al., 1998, J. Surg. Oncol. 68(2):122-38; Lotze et al., 2000, Cancer J. Sci. Am. 6(Suppl 1):S61-6; Cao et al., 1998, Stem Cells 16(Suppl 1):251-60; Kuiper et al., 2000, Adv. Exp. Med. Biol. 465:381-90). These molecules can be administered systemically (or locally) to the host. In several examples, IL-2, RANTES, GM-CSF, TNF-.alpha., IFN-.gamma., G-CSF, LFA-3, CD72, B7-1, B7-2, B7-1 B7-2, OX-40L, 4-1 BBL, and/or ICAM-1 are administered.

[0148] A pharmaceutical composition including one or more polyomavirus capsid polypeptide is thus provided. These compositions are of use to promote an immune response to polyomavirus, such as a BKV serotype-specific response. In some examples, the disclosed compositions include a BKV-IV capsid polypeptide (or a fragment thereof), a BKV-I capsid polypeptide (or a fragment thereof), and a pharmaceutically acceptable carrier. In particular examples, the compositions include a VLP including at least one BKV-IV capsid polypeptide, a VLP including at least one BKV-I capsid polypeptide, and a pharmaceutically acceptable carrier. In other examples, the composition includes a VLP including at least one BKV-Ia capsid polypeptide, a VLP including at least one BKV-Ib2 capsid polypeptide, a VLP including at least one BKV-IV capsid polypeptide, and a pharmaceutically acceptable carrier. In some examples, the compositions further include at least one BKV-II capsid polypeptide, at least one BKV-III capsid polypeptide and/or at least one JCV capsid polypeptide (such as one or more VLPs including at least one BKV-II capsid polypeptide, at least one BKV-III capsid polypeptide, and/or at least one JCV capsid polypeptide). In some embodiments, the compositions include one or more adjuvants.

[0149] In one embodiment, the polyomavirus capsid polypeptide is mixed with an adjuvant containing two or more of a stabilizing detergent, a micelle-forming agent, and an oil. Suitable stabilizing detergents, micelle-forming agents, and oils are detailed in U.S. Pat. No. 5,585,103; U.S. Pat. No. 5,709,860; U.S. Pat. No. 5,270,202; and U.S. Pat. No. 5,695,770, all of which are incorporated by reference. A stabilizing detergent is any detergent that allows the components of the emulsion to remain as a stable emulsion. Such detergents include polysorbate, 80 (TWEEN) (Sorbitan-mono-9-octadecenoate-poly(oxy-1,2-ethanediyl; manufactured by ICI Americas, Wilmington, Del.), TWEEN 40.TM., TWEEN 20.TM., TWEEN 60.TM., ZWITTERGENT.TM. 3-12, TEEPOL HB7.TM., and SPAN 85.TM.. These detergents are usually provided in an amount of approximately 0.05 to 0.5%, such as at about 0.2%. A micelle forming agent is an agent which is able to stabilize the emulsion formed with the other components such that a micelle-like structure is formed. Such agents generally cause some irritation at the site of injection in order to recruit macrophages to enhance the cellular response. Examples of such agents include polymer surfactants described by BASF Wyandotte publications, e.g., Schmolka, J. Am. Oil. Chem. Soc. 54:110, 1977; and Hunter et al., J. Immunol. 127:1244-1250, 1981; for example, PLURONIC.TM. L62LF, L101, and L64, PEG1000, and TETRONIC.TM. 1501, 150R1, 701, 901, 1301, and 130R1. The chemical structures of such agents are well known in the art. In one embodiment, the agent is chosen to have a hydrophile-lipophile balance (HLB) of between 0 and 2, as defined by Hunter and Bennett, J. Immunol. 133:3167-3175, 1984. The agent can be provided in an effective amount, for example between 0.5 and 10%, or in an amount between 1.25 and 5%.

[0150] The oil included in the composition is chosen to promote the retention of the antigen in oil-in-water emulsion, such as to provide a vehicle for the desired antigen, and preferably has a melting temperature of less than 65.degree. C. such that emulsion is formed either at room temperature (about 20.degree. C. to 25.degree. C.), or once the temperature of the emulsion is brought down to room temperature. Examples of such oils include squalene, squalane, EICOSANE.TM., tetratetracontane, glycerol, and peanut oil or other vegetable oils. In one specific, non-limiting example, the oil is provided in an amount between 1 and 10%, or between 2.5 and 5%. The oil should be both biodegradable and biocompatible so that the body can break down the oil over time, and so that no adverse affects, such as granulomas, are evident upon use of the oil.

[0151] In one embodiment, the adjuvant is a mixture of stabilizing detergents, micelle-forming agent, and oil available under the name PROVAX.RTM. (IDEC Pharmaceuticals, San Diego, Calif.). An adjuvant can also be an immunostimulatory nucleic acid, such as a nucleic acid including a CpG motif, or a biological adjuvant (see above).

[0152] Controlled release parenteral formulations can be made as implants, oily injections, or as particulate systems. For a broad overview of protein delivery systems, see Banga, Therapeutic Peptides and Proteins: Formulation, Processing, and Delivery Systems, Technomic Publishing Company, Inc., Lancaster, Pa., 1995. Particulate systems include microspheres, microparticles, microcapsules, nanocapsules, nanospheres, and nanoparticles. Microcapsules contain the therapeutic protein as a central core. In microspheres, the therapeutic agent is dispersed throughout the particle. Particles, microspheres, and microcapsules smaller than about 1 .mu.m are generally referred to as nanoparticles, nanospheres, and nanocapsules, respectively. Capillaries have a diameter of approximately 5 .mu.m so that only nanoparticles are administered intravenously. Microparticles are typically around 100 .mu.m in diameter and are administered subcutaneously or intramuscularly (see Kreuter, Colloidal Drug Delivery Systems, J. Kreuter, ed., Marcel Dekker, Inc., New York, N.Y., pp. 219-342, 1994; Tice & Tabibi, Treatise on Controlled Drug Delivery, A. Kydonieus, ed., Marcel Dekker, Inc. New York, N.Y., pp. 315-339, 1992).

[0153] Polymers can be used for controlled release. Various degradable and nondegradable polymeric matrices for use in controlled drug delivery are known in the art (Langer, Accounts Chem. Res. 26:537, 1993). For example, the block copolymer, polaxamer 407 exists as a viscous yet mobile liquid at low temperatures but forms a semisolid gel at body temperature. It has shown to be an effective vehicle for formulation and sustained delivery of recombinant interleukin-2 and urease (Johnston et al., Pharm. Res. 9:425, 1992; and Pec, J. Parent. Sci. Tech. 44(2):58, 1990). Alternatively, hydroxyapatite has been used as a microcarrier for controlled release of proteins (Ijntema et al., Int. J. Pharm. 112:215, 1994). In yet another aspect, liposomes are used for controlled release as well as drug targeting of the lipid-capsulated drug (Betageri et al., Liposome Drug Delivery Systems, Technomic Publishing Co., Inc., Lancaster, Pa., 1993). Numerous additional systems for controlled delivery of therapeutic proteins are known (e.g., U.S. Pat. Nos. 5,055,303; 5,188,837; 4,235,871; 4,501,728; 4,837,028; 4,957,735; 5,019,369; 5,055,303; 5,514,670; 5,413,797; 5,268,164; 5,004,697; 4,902,505; 5,506,206; 5,271,961; 5,254,342; and 5,534,496).

[0154] In another embodiment, a pharmaceutical composition includes a nucleic acid encoding a polyomavirus capsid polypeptide or fragment thereof (for example, a BKV or JCV capsid polypeptide or fragment). A therapeutically effective amount of the BKV or JCV capsid polynucleotide can be administered to a subject in order to generate an immune response.

[0155] One approach to administration of nucleic acids is direct immunization with plasmid DNA, such as with a mammalian expression plasmid. For example, the nucleotide sequence encoding a polyomavirus capsid polypeptide can be placed under the control of a promoter to increase expression of the molecule.

[0156] Immunization by nucleic acid constructs is well known in the art and taught, for example, in U.S. Pat. No. 5,643,578 (which describes methods of immunizing vertebrates by introducing DNA encoding a desired antigen to elicit a cell-mediated or a humoral response), and U.S. Pat. Nos. 5,593,972 and 5,817,637 (which describe operably linking a nucleic acid sequence encoding an antigen to regulatory sequences enabling expression). U.S. Pat. No. 5,880,103 describes several methods of delivery of nucleic acids encoding immunogenic peptides or other antigens to an organism. The methods include liposomal delivery of the nucleic acids (or of the synthetic peptides themselves), and immune-stimulating constructs, or ISCOMS.TM. (negatively charged cage-like structures of 30-40 nm in size formed spontaneously on mixing cholesterol and saponin). Protective immunity has been generated in a variety of experimental models of infection, including toxoplasmosis and Epstein-Barr virus-induced tumors, using ISCOMS.TM. as the delivery vehicle for antigens (Mowat and Donachie, Immunol. Today 12:383, 1991). Doses of antigen as low as 1 .mu.g encapsulated in ISCOMS.TM. have been found to produce Class I mediated CTL responses (Takahashi et al., Nature 344:873, 1990).

[0157] Optionally, one or more cytokines, such as IL-2, IL-6, IL-12, RANTES, GM-CSF, TNF-.alpha., or IFN-.gamma., one or more growth factors, such as GM-CSF or G-CSF, one or more costimulatory molecules, such as ICAM-1, LFA-3, CD72, B7-1, B7-2, or other B7 related molecules; one or more molecules such as OX-40L or 4-1 BBL, or combinations of these molecules, can be used as biological adjuvants (see, for example, Salgaller et al., 1998, J. Surg. Oncol. 68(2):122-38; Lotze et al., 2000, Cancer J. Sci. Am. 6(Suppl 1):561-6; Cao et al., 1998, Stem Cells 16(Suppl 1):251-60; Kuiper et al., 2000, Adv. Exp. Med. Biol. 465:381-90). These molecules can be administered systemically to the host. It should be noted that these molecules can be co-administered via insertion of a nucleic acid encoding the molecules into a vector, for example, a recombinant pox vector (see, for example, U.S. Pat. No. 6,045,802). In various embodiments, the nucleic acid encoding the biological adjuvant can be cloned into same vector as the BKV polypeptide coding sequence, or the nucleic acid can be cloned into one or more separate vectors for co-administration.

[0158] In one embodiment, a nucleic acid encoding a polyomavirus capsid polypeptide is introduced directly into cells. For example, the nucleic acid can be loaded onto gold microspheres by standard methods and introduced into the skin by a device such as the Helios.TM. Gene Gun (Bio-Rad, Hercules, Calif.). The nucleic acids can be "naked," consisting of plasmids under control of a strong promoter. Typically, the DNA is injected into muscle, although it can also be injected directly into other sites. Dosages for injection are usually around 0.5 .mu.g/kg to about 50 mg/kg, and typically are about 0.005 mg/kg to about 5 mg/kg (see, for example, U.S. Pat. No. 5,589,466).

[0159] In one specific, non-limiting example, a pharmaceutical composition for intravenous administration would include about 0.1 .mu.g to 100 mg of immunogenic polyomavirus capsid polypeptide (or fragment thereof) per patient per day. Dosages from 0.1 to about 100 mg per patient per day (for example, about 10 mg to 50 mg) can be used, particularly if the agent is administered to a secluded site and not into the circulatory or lymph system, such as into a body cavity or into a lumen of an organ. In other non-limiting examples, the pharmaceutical composition includes one or more VLPs including the disclosed polyomavirus capsid polypeptides, for example about 1-200 .mu.g VLP (such as about 10 .mu.g to 200 .mu.g, about 20 .mu.g to 100 .mu.g, or about 20 .mu.g to about 40 .mu.g).

[0160] In some examples, the compositions include pharmaceutically acceptable carriers and/or one or more adjuvants. Actual methods for preparing administrable compositions will be known or apparent to those skilled in the art and are described in more detail in such publications as Remington: The Science and Practice of Pharmacy, The University of the Sciences in Philadelphia, Editor, Lippincott, Williams, & Wilkins, Philadelphia, Pa., 21.sup.st Edition (2005).

[0161] The administration of the polyomavirus capsid polypeptides (or fragments thereof), VLPs including the polypeptides, or nucleic acids encoding the polypeptides can be sequential, simultaneous (concurrent), or substantially simultaneous. Sequential administration can be separated by any amount of time, so long as the desired effect is achieved. In some examples a BKV-I capsid polypeptide or fragment thereof and a BKV-IV capsid polypeptide or fragment thereof are administered to a subject sequentially. In other examples, a BKV-I capsid polypeptide or fragment thereof and a BKV-IV capsid polypeptide or fragment thereof are administered to a subject simultaneously or substantially simultaneously.

[0162] In some examples, the effectiveness of the therapeutic or preventive intervention is monitored by titering the BKV or JCV neutralizing potential of the subject's serum antibody responses over time. Subjects who are found to have been poorly responsive to initial therapeutic interventions, such as but not limited to immunization with BKV or JCV capsid proteins, are given one or more booster doses of the therapeutic intervention.

[0163] Multiple administrations of the compositions described herein are also contemplated. Single or multiple administrations of the compositions are administered, depending on the dosage and frequency as required and tolerated by the subject. In one embodiment, the dosage is administered once as a bolus, but in another embodiment can be applied periodically until a therapeutic result is achieved. In one embodiment, the dose is sufficient to treat or ameliorate symptoms or signs of BKV and/or JCV without producing unacceptable toxicity to the subject. In another embodiment, the dose is sufficient to inhibit infection with BKV upon subsequent exposure to BKV. In other embodiments, the dose is sufficient to inhibit infection with JCV upon subsequent exposure to JCV. In a further embodiment, the dose is sufficient to inhibit a symptom of BKV in a subject with a latent BKV infection. In another embodiment, the dose is sufficient to inhibit a symptom of JCV in a subject with a latent JCV infection. Systemic or local administration can be utilized.

[0164] VI. Methods of Monitoring Immune Response to Polyomavirus

[0165] Also disclosed herein are methods of monitoring an immune response to polyomavirus, for example, following exposure (or potential exposure) to polyomavirus or following immunization against polyomavirus. In some examples, the methods include detecting the presence of polyomavirus antibodies in a subject that has been administered an immunogenic composition comprising at least one isolated BKV capsid polypeptide (or fragment thereof) or a nucleic acid encoding a BKV capsid polypeptide. In other examples, the methods include detecting the presence of polyomavirus antibodies in a subject that has been administered an immunogenic composition comprising at least one isolated JCV capsid polypeptide (or fragment thereof) or a nucleic acid encoding a JCV capsid polypeptide.

[0166] In some examples, the method includes detecting the presence of polyomavirus antibodies (such as neutralizing antibodies) in a sample from a subject (such as a blood sample or serum sample). The polyomavirus antibodies include one or more of BKV-I antibodies (such as BKV-Ia antibodies, BKV-Ib2 antibodies, and/or BKV-Ic antibodies), BKV-II antibodies, BKV-III antibodies, BKV-IV antibodies (such as BKV-IVb1 antibodies and/or BKV-IVc2 antibodies), or JCV antibodies. In some examples, the antibodies are neutralizing antibodies. In some non-limiting examples, the antibodies are BKV-Ia neutralizing antibodies, BKV-Ib2 neutralizing antibodies, or BKV-IV neutralizing antibodies. Monitoring immune response to polyomavirus can indicate whether a subject has developed an immune response (for example, a protective immune response) to one or more polyomaviruses, for example, following administration of an immunogenic composition (for example, as described above). Monitoring immune response to polyomavirus can also indicate whether a subject has seroconverted for one or more polyomaviruses (for example, BKV-I and/or BKV-IV) following an organ transplant or immunosuppressive therapy. In some examples, multiple samples from a subject are tested for presence of antibodies over time, for example prior to and at time points after (such as 1 week, 2 weeks, 1 month, 2 months, 3 months, 6 months, 9 months, 1 year, or more after) administration of an immunogenic composition, organ transplantation or start of immunosuppressive therapy.

[0167] Methods for detecting antibodies in a sample are known to one of skill in the art. Such methods include but are not limited to ELISA, immunofluorescence assay, radioimmunoassay, and micro-agglutination test. In some examples, the methods include detecting the presence of neutralizing antibodies (such as BKV serotype-specific neutralizing antibodies) in a sample from a subject. In some examples, assays for detecting neutralizing antibodies include plaque reduction neutralization test, cell killing, and reporter assays.

[0168] In a particular example, neutralizing antibodies are detected using a reporter assay. BKV or JCV reporter vectors (also known as pseudovirions) are produced by packaging a reporter plasmid in cells (such as 293 cells, for example 293TT cells or 293FT cells for BKV or SVG cells for JCV) expressing a BKV (such as BKV-I, BKV-II, BKV-III, or BKV-IV) or JCV capsid polypeptide (for example, VP1, VP2, and/or VP3). The reporter vector particles are then isolated and treated with serial dilutions of serum from a subject (such as a series of four-fold dilutions from 1:100 to 1:2.6.times.10.sup.7 or a series of 10-fold dilutions from 1:100 to 1.times.10.sup.7). The serum/reporter vector mixture is then applied to fresh cells (for example 293 cells for BKV or SVG cells for JCV) for a period of time (such as 72 hours). The cell culture is then assayed for production of a reporter protein encoded by the reporter plasmid packaged within the reporter vector. A decrease in reporter vector activity (for example, as compared to a control, such as a no serum control) indicates the presence of neutralizing antibodies in the sample. In one example, the reporter plasmid carries an SV40 origin of replication, which can mediate replicative amplification of the transduced plasmid in the target cell. In a specific example, the reporter vector is phGluc (Gaussia princeps luciferase under the control of a human elongation factor 1 alpha promoter) and activity is detected using Gaussia luciferase substrate (New England Biolabs). See, e.g., Pastrana et al., PLoS Pathogens 5(9):e1000578, 2009 (incorporated herein by reference). One of ordinary skill in the art can select additional reporters of use in neutralizing antibody assays, such as green fluorescent protein, .beta.-galactosidase, alkaline phosphatase, and others.

[0169] The present disclosure is illustrated by the following non-limiting Examples.

EXAMPLE 1

Materials and Methods

[0170] Mice: Eight-week old female BALB/cAnNCr mice were immunized once subcutaneously with 5 .mu.g of BKV-I or BKV-IV viral-like particles (VLPs) in complete Freund's Adjuvant (CFA, Sigma-Aldrich, St. Louis, Mo.). Sera were obtained 4 weeks after immunization. The animals were kept under pathogen-free conditions in compliance with institutional guidelines at the National Cancer Institute.

[0171] Sera: Samples from 108 renal transplant subjects from the "Randomized Prospective Controlled Clinical and Pharmacoeconomic Study of Cyclosporine vs. Tacrolimus in Adult Renal Transplant Recipients" of the Washington University, School of Medicine were used. The patients and clinical protocols from the study have previously been described in detail (Bohl et al., Am. J. Transplant. 5:2213-2221; Randhawa et al., Clin. Vaccine Immunol. 15:1564-1571, 2008). Patients were given an immunosuppressive regimen, which was discontinued if viremia was detected. Serum samples were collected at roughly 1, 4, 12, 26 and 52 weeks post-transplantation. None of the patients were observed to suffer from PVAN during the course of the collection period. Sera from healthy subjects visiting U.S. plasma donation centers have been described in detail before (Pastrana et al., PLoS Pathog. 5:e1000578, 2009).

[0172] VLPs and reporter vectors (pseudovirions): BKV reporter vectors were generated as previously described (Pastrana et al., PLoS Pathog. 5:e1000578, 2009). BKV-I reporter vectors were produced using plasmid pCAG-BKV (Nakanishi et al., Virology 379:110-117, 2008), which encodes the capsid proteins of BKV isolate KOM-5 (SEQ ID NOs: 1-3). KOM-5 is classified as a BKV type I subtype b-1 (Ib-1) genotype (Nishimoto et al., J. Mol. Evol. 63:341-352, 2006), and was transfected into 293TT cells (Bucket al., J. Virol. 78:751-757, 2004) using Lipofectamine 2000 (Invitrogen, Carlsbad, Calif.). Then, 48 hours after transfection the cells were suspended at >100 million cells/ml in Dulbecco's phosphate buffered saline (DPBS) and lysed by addition of 0.5% Triton X-100, 25 mM ammonium sulfate (diluted from a 1M stock adjusted to pH 9) and RNase A/T1cocktail (Ambion, Austin, Tex.). The lysate was incubated at 37.degree. C. overnight to allow capsid maturation, then clarified by spinning twice for 10 minutes at 5,000.times.g, with gentle agitation of the lysate between spins. Reporter vector particles were purified out of the clarified supernatant through a 27-33-39% iodixanol (OptiPrep.RTM., Sigma-Aldrich, St. Louis, Mo.) step gradient (Buck and Thompson, Curr. Protoc. Cell Biol. Chapter 26, Unit 26.21, 2007).

[0173] For BKV-IV particles the sequence of BKV isolate A-66H (subtype IV-c2; Zhong et al., J. Gen. Virol. 90:144-152, 2009) was used to design synthetic codon-modified versions of the VP1, VP2 and VP3 genes (SEQ ID NOs: 39-41). The codon-modified genes were synthesized by Blue Heron Biotechnology (Bothell, Wash.) and cloned into Gateway (Invitrogen) adapted mammalian expression plasmids pGwf (for VP1) or phGf (for VP2 and VP3) (Buck et al., Proc. Natl. Acad. Sci. USA 103:1516-1521, 2006). An additional pair of plasmids, pwB2b and pwB3b, were generated by transferring the BKV-IV VP2 or VP3 (respectively) gene into the SV40 promoter-driven expression cassette of pwB. For BKV-IV reporter vector production, cells were co-transfected with pwB2b, pwB3b, ph2b, ph3b and phGluc at a 2:2:1:1:1 ratio. Initial particle stocks produced without ph2b or ph3b in the co-transfection mixture appeared to show poor VP2/3 occupancy and relatively poor infectivity. Transfection, harvesting and purification of BKV-IV reporter vectors were the same as for production of BKV-I reporter vectors.

[0174] For generation of VLPs, 293TT cells were transfected with pCAG-BKV (BKV-I) or a mixture of pwB2b and pwB3b (BKV-IV) without any reporter plasmid. Two days after transfection, the cells were lysed with 0.5% Triton X-100 in DPBS supplemented with 25 mM ammonium sulfate, Benzonase (Sigma-Aldrich), Plasmid Safe (Epicentre, Madison, Wis.), and 1.2 U/ml neuraminidase V (Sigma-Aldrich, Catalog No. N2876). The lysates were incubated at 37.degree. C. overnight, then adjusted to 0.85 M NaCl, clarified as above, and subjected to purification over OptiPrep.RTM. gradients.

[0175] ELISAs: Immulon.TM. H2B plates (Thermo Fisher Scientific, Waltham, Mass.) were coated with 15 ng/well of VLPs in PBS overnight. PBS with 1% non-fat dry milk (blotto) was used to block the coated plates for 2 hours at room temperature, with orbital rotation. Sera from mice and healthy human subjects were serially diluted in blotto and incubated on blocked plates at room temperature for 1 hour, with orbital rotation. Washing was performed with PBS. Horseradish peroxidase conjugated goat anti-mouse IgG (BioRad) or donkey anti-human IgG (Jackson ImmunoResearch, Wes Grove, Pa.) diluted 1:7500 in blotto was used to detect bound sera. The plates were incubated with ABTS (2,2-azino-di43-ethylbenzthiazoine sulfonate) substrate (Roche Applied Science, Indianapolis, Ind.) and absorbance read at 405 nm with a reference read at 490 nm. The effective concentration 10% (EC.sub.10) was calculated using Prism.RTM. software (GraphPad Software, La Jolla, Calif.) to fit a curve to the OD values for each serially-diluted serum sample. The top of each response curve was constrained based on the average of the calculated plateau maximum (Bmax) values for strongly reactive sera. The Bmax value was typically an OD value of around 2.0, such that the EC.sub.10 value can be considered comparable to an OD cutoff value of 0.2.

[0176] Neutralization Assays: Neutralization assays were performed as previously reported (Pastrana et al., PLoS Pathog. 5:e1000578, 2009). Briefly, 293TT cells were seeded at a density of 3.times.10.sup.4 cells per well and allowed to attach for 3-5 hours. Sera from mice and human subjects were serially diluted, and sera from renal transplant patients were tested in separate assays at 4 different dilutions: 1:100, 1:500, 1:5,000, and 1:50,000. Dilutions were performed in cell culture medium (DMEM without phenol red supplemented with 25 mM HEPES, 10% heat-inactivated fetal bovine serum, 1% MEM non-essential amino acids, 1% Glutamax.TM. supplement and 1% antibiotic-antimycotic, all from Invitrogen). Then 24 .mu.l of diluted sera were mixed with 96 .mu.l of diluted reporter vector stock and placed at 4.degree. C. for 1 hour. Cells were incubated with 100 .mu.l of this mixture for 72 hours. Conditioned supernatants (25 .mu.l) were harvested into white 96-well luminometry plates (Perkin Elmer, Waltham, Mass.). Gaussia Luciferase Assay Kit substrate (50 .mu.l, New England Biolabs, Ipswich, Mass.) was injected immediately prior to luminometry using a BMG Labtech Polarstar Optima luminometer.

[0177] For mice and sera from healthy individuals, 50% neutralizing titers (EC50) were calculated based on dose-response curves with top and bottom values constrained to the average values of "no serum" and "no reporter vector" control wells, respectively. For transplant patients, the following criteria for seropositivity and seronegativity were adopted: sera were considered negative at entry if the 1:100 dilution did not mediate at least a 95% reduction in Gaussia luciferase activity (measured in relative light units, RLUs) relative to the no serum control condition (>95% neutralization of the reporter vector). Seroconversion refers to subjects who scored seronegative at the initial time point but whose sera were >95% neutralizing at the 1:500 dilution at any subsequent time point. A stricter definition of seroconversion, accounting for the possible low level cross-type neutralization, added the stipulation that the 95% neutralizing titer for BKV-IV differed from the BKV-I neutralizing titer by less than 1,000 fold.

[0178] Sequence analysis: VP1 sequences from BKV strains indicated in Table 3 (below) were downloaded from GenBank (Pastrana et al., PLoS Pathogens 8:e1002650, 2012; incorporated herein by reference in its entirety). ClustalW alignments were performed with MacVector software version 11.1.2 using a Gonnet series matrix. Structural modeling of BKV VP1 amino acid variations was performed by aligning the sequences of JCV or SV40 VP1 to BKV, followed by inspection of homologous positions of interest in the JCV or SV40 VP1 X-ray crystal structures (PDB ID accession numbers 3NXD and 1SVA, respectively). Structure inspections were performed using Swiss PDB Viewer.

EXAMPLE 2

BKV Cross-Neutralizing Responses in Mouse Sera

[0179] This example describes serological cross-reactivity in mice immunized with VLPs from BKV-I or BKV-IV serotypes.

[0180] To determine if reactivity to one BKV type would generate cross-reactive antibodies, mice were immunized with VLPs containing the VP1, VP2, and VP3 capsid proteins from the two most common serotypes: BKV-I (BKV-Ib1 isolate KOM-5) or BKV-IV (BKV-IVc2 isolate A-66H). A single sub-cutaneous dose in the presence of Freund's adjuvant resulted in the development of high-titer responses. As measured by ELISA, all mice but one responded with titers against BKV-I ranging from 9000 to 110,000 (FIG. 1, top panel). The response in BKV-IV immunized mice was similar, with titers ranging from 13,000 to 130,000. The sera exhibited varying amounts of cross-reactivity against the non-cognate BKV. The average ratio of homologous to heterologous titer was 21 for mice immunized with BKV-I and 110 for mice immunized with BKV-IV (FIG. 1, bottom panel). For this calculation the non-responsive mouse was eliminated, as the denominator was not a true titer, but arbitrarily set at 25, or the lowest concentration tested.

[0181] In order to obtain more information on the cross-neutralizing responses, a reporter-vector based neutralizing assay was also utilized. These recombinant production systems made it possible to generate infectious capsids composed of the VP1/2/3 capsid proteins of BKV primary isolates of genotypes I and IV that are not otherwise culturable. Using the reporter-based assays, the neutralizing potency of sera from BKV-I or BKV-IV vaccinated mice were titered. The neutralizing assay BKV-I, when compared to ELISAs, has been shown to have a broader linear range for detection of serum titers (Pastrana et al., PLoS Pathog. 5:e1000578, 2009), and a similar neutralization assay has also shown improved specificity in the context of papillomaviruses (Pastrana et al., Virology 321:205-216, 2004). The neutralization assays showed a significantly greater degree of BKV type-specificity compared to the ELISAs. For BKV-I immunized mice, homologous titers ranged from 1100 to 3,000,000 (FIG. 1, middle panel). The mouse that was non-reactive by ELISA showed a titer, of 1100, which was 55-fold lower than the next mouse with lower BKV-I titers. Mice immunized with BKV-IV had titers ranging from 17,000 to 600,000. The ratio of homologous to heterologous titer was 910 for mice immunized with BKV-I and 620 for mice immunized with BKV-IV. A comparison of ELISA values to neutralization assay values is shown in FIG. 2.

[0182] To test the possibility that a booster vaccination might alter the degree of cross-neutralization of the two BKV types, a second dose of cognate VLPs was administered to the mice (in incomplete Freund's adjuvant) one month after priming. Repeat serology was performed a total of two months after the initial priming dose. Hyperimmune sera from the boosted animals showed neutralizing ratios similar to the initial testing.

[0183] In addition, mice vaccinated with VLPs based on BKV-Ib2 had serum antibody responses that robustly neutralized the cognate BKV-Ib2 reporter pseudovirus but failed to effectively neutralize the BKC-Ia pseudovirus (Table 2). This result confirms that genotypes BKV-Ia and BKV-Ib2 are distinct serotypes.

TABLE-US-00002 TABLE 2 Single immunization of mice with BKV variants Neutralizing titer (log) Ia Ib2 Ic II III IVb1 IVc2 IMMU- Ia 6.6 3.9 3.6 2.7 neg 2.6 2.0 NIZATION Ib2 neg 4.5 3.6 neg neg 2.3 neg Ic 3.7 3.6 4.2 neg neg 2.8 neg II 2.1 3.5 3.2 4.5 3.5 3.6 3.1 III neg 3.5 3.3 3.4 4.0 2.9 2.9 IVb1 neg 2.9 3.1 2.5 neg 4.6 4.1 IVc2 neg 3.4 3.5 3.0 2.2 3.8 4.2 All 7 types 4.0 3.9 4.1 4.6 4.0 4.7 4.7

[0184] Taken together, the data suggest that the neutralization assay has a larger quantitative dynamic range than ELISA and the neutralization assay is on average about 10 times better at distinguishing BKV type-specific titers (FIG. 1, bottom panel). It is possible that non-neutralizing cross-reactive anti-BKV antibodies are being detected in the ELISA assay but not in the neutralization assay. However, in the context of kidney transplantation, detection of type-specific neutralizing antibodies is more relevant, as only neutralizing antibodies would inhibit de novo infections with a new serotype or suppress latent infections with an existing BKV serotype.

EXAMPLE 3

BKV Titers in Healthy Adults

[0185] Sera from 48 healthy adults with a median age of 52.5 years were assessed for reactivity to BKV-I and BKV-IV in ELISAs. Seroprevalence of different BKV types in these individuals is shown in Table 3. Of these, 83% were seropositive for BKV-I (FIG. 3, top panel), a figure similar to what has been reported in the literature (Egli et al., J. Infect. Dis. 199:837-846, 2009; Knowles et al., J. Med. Virol. 71:115-123, 2003). The geometric mean titer for anti-BKV-I sera was 550 and it ranged from a low of 60 to a high of 7100. In contrast, 65% of volunteers were seropositive for BKV-IV, but their geometric mean titer was only 150, even when they had a similar range (60 to 17,000). In the BKV-IV ELISA, only 18% (9 sera) had a titer higher or equal to 500, while in the BKV-I ELISA 54% (26 sera) reached this titer.

[0186] There was also a statistically significant correlation between BKV-I and BKV-IV titers (Spearman r=0.69, p<0.0001). This correlation, along with the lower geometric mean titers and the knowledge that previous studies have only found 6-7% prevalence of BKV-IV DNA (Krumbholz et al., J. Med. Virol. 78:1588-1598, 2006), indicates that much of the BKV-IV seropositivity is attributable to cross-reactivity in the ELISA assay. The sera were therefore evaluated in the neutralization assay.

TABLE-US-00003 TABLE 3 Seroprevalence of BKV types in 48 healthy individuals Ia Ib2 Ic II III IVb1 IVc2 % Prevalence 79 52 63 58 28 17 28

[0187] For the neutralization assays, serum samples were serially diluted starting at 1:100. This is the lowest naive (rabbit) serum dilution that is consistently devoid of non-specific neutralizing activity (Pastrana et al., PLoS Pathog. 5:e1000578, 2009). Therefore EC.sub.50 values below this dilution could not be accurately calculated and were arbitrarily designated to have an EC.sub.50 of 100. Only 3 volunteers (6%) were negative for BKV-I neutralization. In contrast, 37 (77%) were negative for BKV-IV (FIG. 3, bottom panel). The geometric mean EC.sub.50 titers for BKV-I were also significantly higher (5100) than BKV-IV titers (180). There were three individuals with titers of more than 60,000 for BKV-I that were completely negative for BKV-IV neutralization. In contrast to the ELISA results, there was not a statistically significant correlation between the subjects' BKV-I and BKV-IV neutralizing titers. There were two individuals with BKV-I neutralizing titers of >100,000 whose sera did not detectably neutralize BKV-IV at the lowest tested dilution (1:100). This indicates that these individuals displayed BKV type specificity ratios of at least 1,000. A comparison of ELISA values to neutralization assay values is shown in FIG. 4. Overall, the results for the human sera confirm the observations using murine sera, suggesting that the neutralization assays offer a significantly greater degree of sensitivity and specificity for serological analysis of exposure to BKV-I and BKV-IV.

EXAMPLE 4

BKV Type-Specific Seroconversion in Kidney Transplant Recipients

[0188] The anti-BKV-I and BKV-IV titers of 108 kidney transplant recipients were determined. An archived set of sera collected at time points of roughly 1, 4, 12, 26, and 52 weeks post-transplantation were tested in the neutralization assay. Each sample was tested at four dilutions: 100, 500, 5,000, and 50,000. Because of this lack of full serial dilution, a more stringent neutralization cutoff of 95% for individual data points was utilized. Neutralization assay results for individual subjects are shown in FIGS. 5 and 6. At entry, 5 patients (5%) were seronegative (<95% neutralizing at the 1:100 serum dilution) in the BKV-I neutralization assay (Table 4). In contrast, there were 53 initially BKV-IV seronegative subjects (49%). The patients were then assessed for seroconversion, defined as a change from seronegative at the first time point to at least 95% neutralization at the 1:500 serum dilution at any subsequent time point. All of the 5 initially seronegative BKV-I patients seroconverted for BKV-I, and 23 (43%) of the initially BKV-IV seronegative patients seroconverted for BKV-IV (Table 4).

TABLE-US-00004 TABLE 4 Seroconversion of kidney transplant recipients Negative at entry Seroconversion Stringent Seroconversion (% total) (% initial negative) (% initial negative) BKV-I BKV-IV BKV-I BKV-IV BKV-I BKV-IV 5 (5%) 53 (49%) 5 (100%) 23 (43%) 5 (100%) 12 (23%)

[0189] The average BKV type-specificity ratio for sera from immunized mice was 1359 (FIG. 1). Two human subjects likewise showed type-specificity ratios >1000 (FIG. 3). To address the possibility that BKV-IV neutralization might be partly attributable to cross-reactivity of high titer antibody responses elicited by BKV-I, a more stringent definition of seroconversion was applied, in which the ratio of the BKV-I titer versus the BKV-IV titer (or vice-versa) must be less than 1000 at least one time point to be considered a clear type-specific seroconversion event. Even with these stricter criteria, 12 (23%) of the BKV-IV negative patients seroconverted within a year of transplantation (Table 2). Based on the results shown in FIGS. 1 and 3, the occurrence of BKV type-specificity ratios of 10 or less seems highly unlikely. Five patients (5%) underwent BKV-IV-specific seroconversion by the extremely strict criterion of having a BKV-I to BKV-IV titer ratio <10.

[0190] On average, the patients' BKV-I and BKV-IV neutralizing titers both increased substantially by one year after renal transplantation (FIG. 7). In some instances, titer increases occurred even in patients who showed moderate neutralizing antibody titers at study entry (FIGS. 5 and 6).

EXAMPLE 5

BKV VP1 Protein Sequence Analysis

[0191] Full-length non-identical BKV VP1 peptide sequences available via GenBank were aligned (FIG. 8). The GenBank Accession numbers utilized to generate the alignment are provided in Table 5. Because it is not possible to distinguish between Ia and Ib1 subtypes based on VP1 amino acid sequences, BKV-Ia indicates genotypes Ia/Ib1 and BKV-Ib indicates genotype Ib2. It is also not possible to distinguish between BKV-IV subtypes based on VP1 amino acid sequences. Therefore, BKV-IV indicates genotypes IV-b1/IV-c2.

TABLE-US-00005 TABLE 5 GenBank Accession numbers of aligned BKV VP1 sequences BKV type GenBank Accession Number SEQ ID NO: Ia BAE96059 52 Ia CAA40239 53 Ia BAF02957 54 Ia AAT47395 55 Ia AAT47401 56 Ia BAF42979 57 Ia ABI94689 58 Ia ABI94671 59 Ia AAT47365 60 Ia AAT47389 61 Ia YP_717939 62 Ia AAT47371 63 Ia CAA24307 64 Ia AAT47413 65 Ia AAT47419 66 Ia BAF42937 67 Ia ABI94725 68 Ia AFA41877 69 Ia AFA41907 70 Ia AAT47425 71 Ia AAT47431 72 Ia CAA40243 73 Ia AEK21505 74 Ib ABI94623 75 Ib AFA41920 76 Ib ABI94611 77 Ib BAF42907 78 Ib ABD04662 79 Ib ABI94713 80 Ib CBX88302 81 Ib AFA41880 82 Ib BAF93325 83 Ib CAA40247 84 Ib CBX88314 85 Ib ABI94617 86 Ib BAF93319 87 Ib AAT47347 88 Ib BAF93283 89 Ib BAF03085 90 Ib AFA41909 91 Ib BAF03097 92 Ib ABI94695 93 Ic BAE53660 94 Ic BAE53648 95 Ic CAA40235 96 Ic BAI43588 97 Ic BAE53642 98 Ic BAG75361 99 Ic BAG75283 100 Ic BAF76196 101 Ic ABI94635 102 Ic BAF02975 103 II BAF42901 104 II BAF42925 105 II CAA79596 106 III BAF03017 107 III P14996 108 III AEO89615 109 IV BAF03115 110 IV BAE53654 111 IV BAF75138 112 IV BAE96077 113 IV BAG75277 114 IV BAF75102 115 IV BAF03029 116 IV BAF75180 117 IV AFA41889 118 IV BAF75096 119 IV BAF75114 120 IV AFA41881 121 IV AFA41883 122 IV AFA41885 123 IV BAG84476 124 IV BAF03035 125

[0192] With respect to the BKV-I consensus, BKV-IV isolates tend to carry a variety of substitutions: E61N, N62D, F66Y, K69R, S71T, N74T, D75A, S77D, E82D, Q117K, H139N, 1178V, F225Y, A284P, R340Q, K353R, and K353R, and L362V. Mapping of these BKV-I/BKV-IV variant residues onto homologous positions in the X-ray crystal structures of JCV (Neu et al., Cell Host Microbe 8:309-319, 2010) and SV40 (Stehle et al., Structure 4:165-182, 1996) suggested that, with the exception of positions 117, 225, 284, and 340, each of these BKV-I/BKV-IV variant residues is likely to be exposed on the exterior surface of the capsid. With the exception of residues 353 and 362, which are exposed along the floor of the canyons between capsomer knobs, all the exposed variations map to sites on the apical surface and apical rim of the capsomer knob. Many of the variations are adjacent to residues predicted to be involved in binding the cellular glycolipids that serve as receptors during BKV infectious entry (Dugan et al., J. Virol, 81:1179841808, 2007; Low et al., J. Virol. 80:1361-1366, 2006). This is consistent with the idea that BKV-I/BKV-IV variations may alter epitopes recognized by antibodies that neutralize infectivity via steric occlusion of the receptor binding site.

[0193] In addition to the differences between BKV4 and BKV-IV, several positions differ stereotypically among BKV-I subtypes. For example, BKV subtype Ib-2 isolates tend to carry V42L, E82D, D175E, V210I, R340K, and L362V differences, with respect to subtypes Ia and Ib-1. Likewise, subtype Ic isolates frequently carry E20D, F225L, and R340K differences. Although these intra-genotype-I surface variations are chemically subtle, without being bound by theory, it is possible that the differences reflect selective pressure to escape neutralizing antibodies.

[0194] In human subjects, it was found that 6 of 48 subjects with BKV-la neutralizing antibodies were not able to neutralize a BKV-Ib2 isolate (including VP1 polypeptide with the amino acid sequence of SEQ ID NO: 14). Analysis of mutant pseudoviruses that are recombinant chimeras of types Ia and Ib2, identified key amino acid residues that allow the Ib2 isolate to escape from IL-neutralizing antibody response. The variations were in the VPI BC loop and included E73K and E82D) (Ia to Ib2 variations). Several other Ib2 variants and genotype, Ic BC loop variations were partially resistant to Ia-neutralizing human sera. These additional variants included E73Q, S77N, E82Q, or combinations of these variations. These results suggest that an optimal BKV vaccine should include at least BKV-Ia and BKV-Ib2 VP1 polypeptides, in order to elicit antibodies capable of neutralizing all BKV-I variants. Furthermore, validation of a candidate vaccine should include screening serum from vaccinated subjects for neutralization of multiple BKV-I subtypes (such as at least BKV-Ia and BKV-Ib2 subtypes)

EXAMPLE 6

Additional BKV VP1 Polypeptides

[0195] Additional BKV serotypes may remain to be discovered and fully sequenced. GenBank accession numbers CCF70703-CCF70735 report a portion of the VP1 protein encompassing the BC and EF loops. Some of these sequences contain previously unknown variations in the BC and EF loops. In some instances, the sequence fragments are more divergent from all published BKV VP1 sequences than BKV-I is from BKV-IV (FIG. 9). Based on the an alignment of these additional sequences with BKV-Ia, BKV-Ib, BKV-Ic, BKV-II, BKV-III, BKV-IVb1, and BKV-IVc2 VP1 sequences (FIG. 10), accession numbers CCF70725 (SEQ ID NO: 154), CCF70727 (SEQ ID NO: 153), CCF70729 (SEQ ID NO: 158), and CCF70730 (SEQ ID NO: 157) appear to represent portions of distinct BKV serotypes. The GenBank Accession numbers utilized to generate the alignment are provided in Table 6. The serological distinctiveness of these recently reported sequences can be determined, for example by isolating the remainder of these VP1 sequences and using the methods described in Examples 1 and 2. Polypeptides comprising these additional BKV VP1 polypeptides can be utilized in the disclosed methods and compositions. In some cases, the disclosed methods and compositions include one or more of SEQ ID NOs: 126-158.

TABLE-US-00006 TABLE 6 GenBank Accession Nos. of additional partial BKV VP1 sequences GenBank Accession No. SEQ ID NO: CCF70703 126 CCF70704 127 CCF70705 128 CCF70706 129 CCF70707 130 CCF70708 131 CCF70709 132 CCF70710 133 CCF70711 134 CCF70712 135 CCF70713 136 CCF70714 137 CCF70715 138 CCF70716 139 CCF70717 140 CCF70718 141 CCF70719 142 CCF70720 143 CCF70722 144 CCF70723 145 CCF70724 146 CCF70726 147 CCF70728 148 CCF70732 149 CCF70733 150 CCF70734 151 CCF70735 152 CCF70727 153 CCF70725 154 CCF70731 155 CCF70721 156 CCF70730 157 CCF70729 158

EXAMPLE 7

Methods of Eliciting an Immune Response to BKV

[0196] This example provides exemplary methods for eliciting an immune response to one or more BKV serotypes in a subject. However, one of ordinary skill in the art will appreciate that methods that deviate from these specific methods can also be used to successfully elicit an immune response to BKV in a subject.

[0197] In particular examples, the method includes selecting a subject in need of enhanced immunity to BKV. Subjects in need of enhanced immunity to BKV include individuals who are immunocompromised and individuals who have had or are candidates for organ transplantation, for example a renal transplant or bone marrow transplant. Subjects in need of enhanced immunity to BKV also include individuals who are seronegative for at least one BKV serotype.

[0198] Subjects selected for treatment are administered a therapeutically effective amount of a disclosed immunogenic composition. In some examples, a therapeutically effective amount of one or more BKV-I capsid polypeptides (or fragments thereof) or one or more polynucleotides encoding the BKV-I capsid polypeptides and a therapeutically effective amount of one or more BKV-IV capsid polypeptides (or fragments thereof) or one or more polynucleotides encoding the BKV-IV capsid polypeptides is administered to the subject at doses of about 0.1 .mu.g to 10 mg of each BKV capsid polypeptide or polynucleotide encoding the polypeptide or about 20-40 .mu.g VLP per type for pentamers. However, the particular dose can be determined by a skilled clinician. The disclosed BKV capsid polypeptides (or a fragment thereof) or polynucleotide encoding the BKV capsid polypeptides or fragment thereof can be administered in one or several doses, for example continuously, daily, weekly, or monthly. When administered sequentially, the time separating the administration can be seconds, minutes, hours, days, or even weeks.

[0199] The mode of administration can be any used in the art, including but not limited to subcutaneous or intramuscular administration. The amount of agent administered to the subject can be determined by a clinician, and may depend on the particular subject treated. Specific exemplary amounts are provided herein (but the disclosure is not limited to such doses).

[0200] The development of immune response (such as development of antibodies, such as neutralizing antibodies) in a subject is monitored at time points following administration of the immunogenic composition. Methods of detecting antibodies in a sample (such as a blood or serum sample) include those known in the art, for example, ELISA methods. In some examples, the development of neutralizing antibodies to a BKV-Ia and/or BKV-Ib1 subtype and development of neutralizing antibodies to BKV-Ib2 subtype are monitored.

EXAMPLE 8

Methods of Treating or Inhibiting PVAN

[0201] This example provides exemplary methods for treating or inhibiting PVAN in a subject. However, one of ordinary skill in the art will appreciate that methods that deviate from these specific methods can also be used to successfully treat or inhibit PVAN in a subject.

[0202] In particular examples, the method includes selecting a subject having, thought to have, or at risk of having PVAN. Subjects having or thought to have PVAN include those with >10 inclusion bearing epithelial cells ("decoy cells") in a urine sample per 10 high power fields, >10.sup.7 BKV copies per 10 mL urine, or histopathological identification of viral alterations in a renal biopsy. Subjects at risk of PVAN include those who have had or are candidates for organ transplantation (such as renal transplant or bone marrow transplant), and immunocompromised individuals. In some examples, subjects who are candidates for renal transplant are selected. The selected subject can be a subject who does not have BKV-IV neutralizing antibodies.

[0203] Subjects selected for treatment are administered a therapeutically effective amount of a disclosed immunogenic composition. In some examples, a therapeutically effective amount of one or more BKV-IV capsid polypeptides or a polynucleotide encoding the BKV-IV capsid polypeptide(s) is administered to the subject at doses of about 0.1 .mu.g to 10 mg of each BKV-IV capsid polypeptide or polynucleotide encoding the polypeptide or about 20-40 .mu.g VLP per type for pentamers. However, the particular dose can be determined by a skilled clinician. The disclosed BKV-IV capsid polypeptides (or a fragment thereof) or polynucleotide encoding the BKV-IV capsid polypeptides or fragment thereof can be administered in one or several doses, for example continuously, daily, weekly, or monthly, with at least one dose at least 2 weeks prior to transplant. When administered sequentially, the time separating the administration can be seconds, minutes, hours, days, or even weeks.

[0204] The mode of administration can be any used in the art, including but not limited to subcutaneous or intramuscular administration. The amount of agent administered to the subject can be determined by a clinician, and may depend on the particular subject treated. Specific exemplary amounts are provided herein (but the disclosure is not limited to such doses).

[0205] The development of immune response (such as development of antibodies, such as neutralizing antibodies) in a subject is monitored at time points following administration of the immunogenic composition. Methods of detecting antibodies in a sample (such as a blood or serum sample) include those known in the art, for example, ELISA methods. A renal transplant is performed after an immune response is detected. The subject is also monitored for development of PVAN, for example by testing for presence of virus in urine or renal biopsy.

EXAMPLE 9

Methods of Identifying a Renal Transplant Donor

[0206] This example provides exemplary methods for identifying a renal transplant donor, such as an individual who does not have serum antibodies capable of neutralizing one or more BKV types. However, one of ordinary skill in the art will appreciate that methods that deviate from these specific methods can also be used to successfully identify a renal transplant donor.

[0207] A blood sample is collected from a subject who is considered a possible renal transplant donor. Serum is prepared from the sample and serial dilutions of the serum are prepared (e.g., ten serial dilutions of four-fold ranging from 1:100 to 2.6.times.10.sup.7). The diluted serum is mixed with a diluted BKV reporter vector carrying a reporter plasmid encoding Gaussia princeps luciferase under the control of a human elongation factor 1 alpha promoter and incubated on ice or at 4.degree. C. for 1 hour. Then, the virus/serum mixture is added to 293TT cells plated in a 96-well plate at 3.times.10.sup.4 cells/well. After 3 days, 25 .mu.l of conditioned medium is collected and transferred to a luminometry plate. Gaussia luciferase substrate (50 .mu.l NEB Gaussia luciferase assay kit substrate) is added and light emission is detected using a luminometer. Effective concentration 50% (EC.sub.50) is calculated for the serum dilution series. An EC50 of less than 100 indicates that the subject does not have BKV-IV neutralizing antibodies. A subject who does not have BKV-IV neutralizing antibodies is selected as a renal transplant donor.

[0208] A candidate renal transplant recipient can also be screened for the presence of BKV-IV neutralizing antibodies as described above. A candidate renal transplant recipient who is negative for BKV-IV neutralizing antibodies is considered a good candidate for receiving a kidney from a renal transplant donor who is negative for BKV-IV neutralizing antibodies.

[0209] Similar screening can be done for the presence of other BKV type-specific neutralizing antibodies in potential renal transplant donors and/or recipients. A potential renal transplant donor who does not have particular type-specific (such as BKV-I, BKV-II, or BKV-III) neutralizing antibodies is identified and selected as a renal transplant donor, particularly for a renal transplant recipient who also does not have the same type-specific neutralizing antibodies.

[0210] In view of the many possible embodiments to which the principles of the disclosure may be applied, it should be recognized that the illustrated embodiments are only examples and should not be taken as limiting the scope of the invention. Rather, the scope of the invention is defined by the following claims. We therefore claim as our invention all that comes within the scope and spirit of these claims.

Sequence CWU 1

1

1581362PRTBK virus 1Met Ala Pro Thr Lys Arg Lys Gly Glu Cys Pro Gly Ala Ala Pro Lys 1 5 10 15 Lys Pro Lys Glu Pro Val Gln Val Pro Lys Leu Leu Ile Lys Gly Gly 20 25 30 Val Glu Val Leu Glu Val Lys Thr Gly Val Asp Ala Ile Thr Glu Val 35 40 45 Glu Cys Phe Leu Asn Pro Glu Met Gly Asp Pro Asp Glu Asn Leu Arg 50 55 60 Gly Phe Ser Leu Lys Leu Ser Ala Glu Asn Asp Phe Ser Ser Asp Ser 65 70 75 80 Pro Glu Arg Lys Met Leu Pro Cys Tyr Ser Thr Ala Arg Ile Pro Leu 85 90 95 Pro Asn Leu Asn Glu Asp Leu Thr Cys Gly Asn Leu Leu Met Trp Glu 100 105 110 Ala Val Thr Val Gln Thr Glu Val Ile Gly Ile Thr Ser Met Leu Asn 115 120 125 Leu His Ala Gly Ser Gln Lys Val His Glu His Gly Gly Gly Lys Pro 130 135 140 Ile Gln Gly Ser Asn Phe His Phe Phe Ala Val Gly Gly Asp Pro Leu 145 150 155 160 Glu Met Gln Gly Val Leu Met Asn Tyr Arg Thr Lys Tyr Pro Asp Gly 165 170 175 Thr Ile Thr Pro Lys Asn Pro Thr Ala Gln Ser Gln Val Met Asn Thr 180 185 190 Asp His Lys Ala Tyr Leu Asp Lys Asn Asn Ala Tyr Pro Val Glu Cys 195 200 205 Trp Val Pro Asp Pro Ser Arg Asn Glu Asn Thr Arg Tyr Phe Gly Thr 210 215 220 Phe Thr Gly Gly Glu Asn Val Pro Pro Val Leu His Val Thr Asn Thr 225 230 235 240 Ala Thr Thr Val Leu Leu Asp Glu Gln Gly Val Gly Pro Leu Cys Lys 245 250 255 Ala Asp Ser Leu Tyr Val Ser Ala Ala Asp Ile Cys Gly Leu Phe Thr 260 265 270 Asn Ser Ser Gly Thr Gln Gln Trp Arg Gly Leu Ala Arg Tyr Phe Lys 275 280 285 Ile Arg Leu Arg Lys Arg Ser Val Lys Asn Pro Tyr Pro Ile Ser Phe 290 295 300 Leu Leu Ser Asp Leu Ile Asn Arg Arg Thr Gln Arg Val Asp Gly Gln 305 310 315 320 Pro Met Tyr Gly Met Glu Ser Gln Val Glu Glu Val Arg Val Phe Asp 325 330 335 Gly Thr Glu Arg Leu Pro Gly Asp Pro Asp Met Ile Arg Tyr Ile Asp 340 345 350 Lys Gln Gly Gln Leu Gln Thr Lys Met Leu 355 360 2351PRTBK virus 2Met Gly Ala Ala Leu Ala Leu Leu Gly Asp Leu Val Ala Ser Val Ser 1 5 10 15 Glu Ala Ala Ala Ala Thr Gly Phe Ser Val Ala Glu Ile Ala Ala Gly 20 25 30 Glu Ala Ala Ala Ala Ile Glu Val Gln Ile Ala Ser Leu Ala Thr Val 35 40 45 Glu Gly Ile Thr Ser Thr Ser Glu Ala Leu Ala Ala Ile Gly Leu Thr 50 55 60 Pro Gln Thr Tyr Ala Val Ile Ala Gly Ala Pro Gly Ala Ile Ala Gly 65 70 75 80 Phe Ala Ala Leu Ile Gln Thr Val Thr Gly Ile Ser Ser Leu Ala Gln 85 90 95 Val Gly Tyr Arg Phe Phe Ser Asp Trp Asp His Lys Val Ser Thr Val 100 105 110 Gly Leu Tyr Gln Gln Ser Gly Met Ala Leu Glu Leu Phe Asn Pro Asp 115 120 125 Glu Tyr Tyr Asp Ile Leu Phe Pro Gly Val Asn Thr Phe Val Asn Asn 130 135 140 Ile Gln Tyr Leu Asp Pro Arg His Trp Gly Pro Ser Leu Phe Ala Thr 145 150 155 160 Ile Ser Gln Ala Leu Trp His Val Ile Arg Asp Asp Ile Pro Ala Ile 165 170 175 Thr Ser Gln Glu Leu Gln Arg Arg Thr Glu Arg Phe Phe Arg Asp Ser 180 185 190 Leu Ala Arg Phe Leu Glu Glu Thr Thr Trp Thr Ile Val Asn Ala Pro 195 200 205 Ile Asn Phe Tyr Asn Tyr Ile Gln Glu Tyr Val Ser Asp Leu Ser Pro 210 215 220 Ile Arg Pro Ser Met Val Arg Gln Val Ala Glu Arg Glu Gly Thr Arg 225 230 235 240 Val His Phe Gly His Thr Tyr Ser Ile Asp Asp Ala Asp Ser Ile Glu 245 250 255 Glu Val Thr Gln Arg Met Asp Leu Arg Asn Gln Gln Thr Val His Ser 260 265 270 Gly Glu Phe Ile Glu Lys Thr Ile Ala Pro Gly Gly Ala Asn Gln Arg 275 280 285 Thr Ala Pro Gln Trp Met Leu Pro Leu Leu Leu Gly Leu Tyr Gly Thr 290 295 300 Val Thr Pro Ala Leu Glu Ala Tyr Glu Asp Gly Pro Asn Gln Lys Lys 305 310 315 320 Arg Arg Val Ser Arg Gly Ser Ser Gln Lys Ala Lys Gly Thr Arg Ala 325 330 335 Ser Ala Lys Thr Thr Asn Lys Arg Arg Ser Arg Ser Ser Arg Ser 340 345 350 3232PRTBK virus 3Met Ala Leu Glu Leu Phe Asn Pro Asp Glu Tyr Tyr Asp Ile Leu Phe 1 5 10 15 Pro Gly Val Asn Thr Phe Val Asn Asn Ile Gln Tyr Leu Asp Pro Arg 20 25 30 His Trp Gly Pro Ser Leu Phe Ala Thr Ile Ser Gln Ala Leu Trp His 35 40 45 Val Ile Arg Asp Asp Ile Pro Ala Ile Thr Ser Gln Glu Leu Gln Arg 50 55 60 Arg Thr Glu Arg Phe Phe Arg Asp Ser Leu Ala Arg Phe Leu Glu Glu 65 70 75 80 Thr Thr Trp Thr Ile Val Asn Ala Pro Ile Asn Phe Tyr Asn Tyr Ile 85 90 95 Gln Glu Tyr Tyr Ser Asp Leu Ser Pro Ile Arg Pro Ser Met Val Arg 100 105 110 Gln Val Ala Glu Arg Glu Gly Thr Arg Val His Phe Gly His Thr Tyr 115 120 125 Ser Ile Asp Asp Ala Asp Ser Ile Glu Glu Val Thr Gln Arg Met Asp 130 135 140 Leu Arg Asn Gln Gln Thr Val His Ser Gly Glu Phe Ile Glu Lys Thr 145 150 155 160 Ile Ala Pro Gly Gly Ala Asn Gln Arg Thr Ala Pro Gln Trp Met Leu 165 170 175 Pro Leu Leu Leu Gly Leu Tyr Gly Thr Val Thr Pro Ala Leu Glu Ala 180 185 190 Tyr Glu Asp Gly Pro Asn Gln Lys Lys Arg Arg Val Ser Arg Gly Ser 195 200 205 Ser Gln Lys Ala Lys Gly Thr Arg Ala Ser Ala Lys Thr Thr Asn Lys 210 215 220 Arg Arg Ser Arg Ser Ser Arg Ser 225 230 4362PRTBK virus 4Met Ala Pro Thr Lys Arg Lys Gly Glu Cys Pro Gly Ala Ala Pro Lys 1 5 10 15 Lys Pro Lys Glu Pro Val Gln Val Pro Lys Leu Leu Ile Lys Gly Gly 20 25 30 Val Glu Val Leu Glu Val Lys Thr Gly Val Asp Ala Ile Thr Glu Val 35 40 45 Glu Cys Phe Leu Asn Pro Glu Met Gly Asp Pro Asp Asn Asp Leu Arg 50 55 60 Gly Tyr Ser Leu Arg Leu Thr Ala Glu Thr Ala Phe Asp Ser Asp Ser 65 70 75 80 Pro Asp Arg Lys Met Leu Pro Cys Tyr Ser Thr Ala Arg Ile Pro Leu 85 90 95 Pro Asn Leu Asn Glu Asp Leu Thr Cys Gly Asn Leu Leu Met Trp Glu 100 105 110 Ala Val Thr Val Lys Thr Glu Val Ile Gly Ile Thr Ser Met Leu Asn 115 120 125 Leu His Ala Gly Ser Gln Lys Val His Glu Asn Gly Gly Gly Lys Pro 130 135 140 Ile Gln Gly Ser Asn Phe His Phe Phe Ala Val Gly Gly Asp Pro Leu 145 150 155 160 Glu Met Gln Gly Val Leu Met Asn Tyr Arg Thr Lys Tyr Pro Glu Gly 165 170 175 Thr Val Thr Pro Lys Asn Pro Thr Ala Gln Ser Gln Val Met Asn Thr 180 185 190 Asp His Lys Ala Tyr Leu Asp Lys Asn Asn Ala Tyr Pro Val Glu Cys 195 200 205 Trp Ile Pro Asp Pro Ser Lys Asn Glu Asn Thr Arg Tyr Phe Gly Thr 210 215 220 Tyr Thr Gly Gly Glu Asn Val Pro Pro Val Leu His Val Thr Asn Thr 225 230 235 240 Ala Thr Thr Val Leu Leu Asp Glu Gln Gly Val Gly Pro Leu Cys Lys 245 250 255 Ala Asp Ser Leu Tyr Val Ser Ala Ala Asp Ile Cys Gly Leu Phe Thr 260 265 270 Asn Ser Ser Gly Thr Gln Gln Trp Arg Gly Leu Pro Arg Tyr Phe Lys 275 280 285 Ile Arg Leu Arg Lys Arg Ser Val Lys Asn Pro Tyr Pro Ile Ser Phe 290 295 300 Leu Leu Ser Asp Leu Ile Asn Arg Arg Thr Gln Arg Val Asp Gly Gln 305 310 315 320 Pro Met Tyr Gly Met Glu Ser Gln Val Glu Glu Val Arg Val Phe Asp 325 330 335 Gly Thr Glu Gln Leu Pro Gly Asp Pro Asp Met Ile Arg Tyr Ile Asp 340 345 350 Arg Gln Gly Gln Leu Gln Thr Lys Met Val 355 360 5351PRTBK virus 5Met Gly Ala Ala Leu Ala Leu Leu Gly Asp Leu Val Ala Ser Val Ser 1 5 10 15 Glu Ala Ala Ala Ala Thr Gly Phe Ser Val Ala Glu Ile Ala Ala Gly 20 25 30 Glu Ala Ala Ala Ala Ile Glu Val Gln Ile Ala Ser Leu Ala Thr Val 35 40 45 Glu Gly Ile Thr Ser Thr Ser Glu Ala Ile Ala Ala Ile Gly Leu Thr 50 55 60 Pro Gln Thr Tyr Ala Val Ile Ala Gly Ala Pro Gly Ala Ile Ala Gly 65 70 75 80 Phe Ala Ala Leu Ile Gln Thr Val Thr Gly Ile Ser Ser Leu Ala Gln 85 90 95 Val Gly Tyr Arg Phe Phe Ser Asp Trp Asp His Lys Val Ser Thr Val 100 105 110 Gly Leu Tyr Gln Gln Ser Gly Met Ala Leu Glu Leu Phe Asn Pro Asp 115 120 125 Glu Tyr Tyr Asp Ile Leu Phe Pro Gly Val Asn Thr Phe Val Asn Asn 130 135 140 Ile Gln Tyr Leu Asp Pro Arg His Trp Gly Pro Ser Leu Phe Ala Thr 145 150 155 160 Ile Ser Gln Ala Leu Trp His Val Ile Arg Asp Asp Ile Pro Ala Ile 165 170 175 Thr Ser Gln Glu Leu Gln Arg Arg Thr Glu Arg Phe Phe Arg Asp Ser 180 185 190 Leu Ala Arg Phe Leu Glu Glu Thr Thr Trp Thr Ile Val Asn Ala Pro 195 200 205 Val Asn Phe Tyr Asn Tyr Ile Gln Asp Tyr Tyr Ser Asn Leu Ser Pro 210 215 220 Ile Arg Pro Ser Met Val Arg Gln Val Ala Glu Arg Glu Gly Thr Gln 225 230 235 240 Val Asn Phe Gly His Thr Tyr Arg Ile Asp Asp Ala Asp Ser Ile Gln 245 250 255 Glu Val Thr Gln Arg Met Glu Leu Arg Asn Lys Glu Asn Val His Ser 260 265 270 Gly Glu Phe Ile Glu Lys Thr Ile Ala Pro Gly Gly Ala Asn Gln Arg 275 280 285 Thr Ala Pro Gln Trp Met Leu Pro Leu Leu Leu Gly Leu Tyr Gly Thr 290 295 300 Val Thr Pro Ala Leu Glu Ala Tyr Glu Asp Gly Pro Asn Gln Lys Lys 305 310 315 320 Arg Arg Val Ser Arg Gly Ser Ser Gln Lys Ala Lys Gly Thr Arg Ala 325 330 335 Ser Ala Lys Thr Thr Asn Lys Arg Arg Ser Arg Ser Ser Arg Ser 340 345 350 6232PRTBK virus 6Met Ala Leu Glu Leu Phe Asn Pro Asp Glu Tyr Tyr Asp Ile Leu Phe 1 5 10 15 Pro Gly Val Asn Thr Phe Val Asn Asn Ile Gln Tyr Leu Asp Pro Arg 20 25 30 His Trp Gly Pro Ser Leu Phe Ala Thr Ile Ser Gln Ala Leu Trp His 35 40 45 Val Ile Arg Asp Asp Ile Pro Ala Ile Thr Ser Gln Glu Leu Gln Arg 50 55 60 Arg Thr Glu Arg Phe Phe Arg Asp Ser Leu Ala Arg Phe Leu Glu Glu 65 70 75 80 Thr Thr Trp Thr Ile Val Asn Ala Pro Val Asn Phe Tyr Asn Tyr Ile 85 90 95 Gln Asp Tyr Tyr Ser Asn Leu Ser Pro Ile Arg Pro Ser Met Val Arg 100 105 110 Gln Val Ala Glu Arg Glu Gly Thr Gln Val Asn Phe Gly His Thr Tyr 115 120 125 Arg Ile Asp Asp Ala Asp Ser Ile Gln Glu Val Thr Gln Arg Met Glu 130 135 140 Leu Arg Asn Lys Glu Asn Val His Ser Gly Glu Phe Ile Glu Lys Thr 145 150 155 160 Ile Ala Pro Gly Gly Ala Asn Gln Arg Thr Ala Pro Gln Trp Met Leu 165 170 175 Pro Leu Leu Leu Gly Leu Tyr Gly Thr Val Thr Pro Ala Leu Glu Ala 180 185 190 Tyr Glu Asp Gly Pro Asn Gln Lys Lys Arg Arg Val Ser Arg Gly Ser 195 200 205 Ser Gln Lys Ala Lys Gly Thr Arg Ala Ser Ala Lys Thr Thr Asn Lys 210 215 220 Arg Arg Ser Arg Ser Ser Arg Ser 225 230 7362PRTBK virus 7Met Ala Pro Thr Lys Arg Lys Gly Glu Cys Pro Gly Ala Ala Pro Lys 1 5 10 15 Lys Pro Lys Glu Pro Val Gln Val Pro Lys Leu Leu Ile Lys Gly Gly 20 25 30 Val Glu Val Leu Glu Val Lys Thr Gly Val Asp Ala Ile Thr Glu Val 35 40 45 Glu Cys Phe Leu Asn Pro Glu Met Gly Asp Pro Asp Asn Asp Leu Arg 50 55 60 Gly Tyr Ser Leu Lys Leu Thr Ala Glu Asn Ala Phe Asp Ser Asp Ser 65 70 75 80 Pro Asp Lys Lys Met Leu Pro Cys Tyr Ser Thr Ala Arg Ile Pro Leu 85 90 95 Pro Asn Leu Asn Glu Asp Leu Thr Cys Gly Asn Leu Leu Met Trp Glu 100 105 110 Ala Val Thr Val Lys Thr Glu Val Ile Gly Ile Thr Ser Met Leu Asn 115 120 125 Leu His Ala Gly Ser Gln Lys Val His Glu Asn Gly Gly Gly Lys Pro 130 135 140 Val Gln Gly Ser Asn Phe His Phe Phe Ala Val Gly Gly Asp Pro Leu 145 150 155 160 Glu Met Gln Gly Val Leu Met Asn Tyr Arg Thr Lys Tyr Pro Gln Gly 165 170 175 Thr Ile Thr Pro Lys Asn Pro Thr Ala Gln Ser Gln Val Met Asn Thr 180 185 190 Asp His Lys Ala Tyr Leu Asp Lys Asn Asn Ala Tyr Pro Val Glu Cys 195 200 205 Trp Ile Pro Asp Pro Ser Arg Asn Glu Asn Thr Arg Tyr Phe Gly Thr 210 215 220 Tyr Thr Gly Gly Glu Asn Val Pro Pro Val Leu His Val Thr Asn Thr 225 230 235 240 Ala Thr Thr Val Leu Leu Asp Glu Gln Gly Val Gly Pro Leu Cys Lys 245 250 255 Ala Asp Ser Leu Tyr Val Ser Ala Ala Asp Ile Cys Gly Leu Phe Thr 260 265 270 Asn Ser Ser Gly Thr Gln Gln Trp Arg Gly Leu Ala Arg Tyr Phe Lys 275 280 285 Ile Arg Leu Arg Lys Arg Ser Val Lys Asn Pro Tyr Pro Ile Ser Phe 290 295 300 Leu Leu Ser Asp Leu Ile Asn Arg Arg Thr Gln Lys Val Asp Gly Gln 305 310 315 320 Pro Met Tyr Gly Met Glu Ser Gln Val Glu Glu Val Arg Val Phe Asp 325 330 335 Gly Thr Glu Gln Leu Pro Gly Asp Pro Asp Met Ile Arg Tyr Ile Asp 340 345 350 Arg Gln Gly Gln Leu Gln Thr Lys Met Val 355 360 8351PRTBK virus 8Met Gly Ala Ala Leu Ala Leu Leu Gly Asp Leu Val Ala Ser Val Ser 1 5 10 15 Glu Ala Ala Ala Ala Thr Gly Phe Ser Val Ala Glu Ile Ala Ala Gly 20 25 30 Glu Ala Ala Ala Ala

Ile Glu Val Gln Ile Ala Ser Leu Ala Thr Val 35 40 45 Glu Gly Ile Thr Thr Thr Ser Glu Ala Ile Ala Ala Ile Gly Leu Thr 50 55 60 Pro Gln Thr Tyr Ala Val Ile Ala Gly Ala Pro Gly Ala Ile Ala Gly 65 70 75 80 Phe Ala Ala Leu Ile Gln Thr Val Thr Gly Ile Ser Ser Leu Ala Gln 85 90 95 Val Gly Tyr Arg Phe Phe Ser Asp Trp Asp His Lys Val Ser Thr Val 100 105 110 Gly Leu Tyr Gln Gln Ser Gly Met Ala Leu Glu Leu Phe Asn Pro Asp 115 120 125 Glu Tyr Tyr Asp Ile Leu Phe Pro Gly Val Asn Thr Phe Val Asn Asn 130 135 140 Ile Gln Tyr Leu Asp Pro Arg His Trp Gly Pro Ser Leu Phe Ala Thr 145 150 155 160 Ile Ser Gln Ala Leu Trp His Val Ile Arg Asp Asp Ile Pro Ala Ile 165 170 175 Thr Ser Gln Glu Leu Gln Arg Arg Thr Glu Arg Phe Phe Arg Asp Ser 180 185 190 Leu Ala Arg Phe Leu Glu Glu Thr Thr Trp Thr Ile Val Asn Ala Pro 195 200 205 Val Asn Phe Tyr Asn Tyr Ile Gln Asp Tyr Tyr Ser Asn Leu Ser Pro 210 215 220 Ile Arg Pro Ser Met Val Arg Gln Val Ala Glu Arg Glu Gly Thr His 225 230 235 240 Val Asn Phe Gly His Thr Tyr Ser Ile Asp Asp Ala Asp Ser Ile Glu 245 250 255 Glu Val Thr Gln Arg Ile Glu Leu Arg Asn Lys Glu Ser Val His Ser 260 265 270 Gly Glu Phe Ile Glu Lys Thr Ile Ala Pro Gly Gly Ala Asn Gln Arg 275 280 285 Thr Ala Pro Gln Trp Met Leu Pro Leu Leu Leu Gly Leu Tyr Gly Thr 290 295 300 Val Thr Pro Ala Leu Glu Ala Tyr Glu Asp Gly Pro Asn Gln Lys Lys 305 310 315 320 Arg Arg Val Ser Arg Gly Ser Ser Gln Lys Ala Lys Gly Thr Arg Ala 325 330 335 Ser Ala Lys Thr Thr Asn Lys Arg Arg Ser Arg Ser Ser Arg Ser 340 345 350 9232PRTBK virus 9Met Ala Leu Glu Leu Phe Asn Pro Asp Glu Tyr Tyr Asp Ile Leu Phe 1 5 10 15 Pro Gly Val Asn Thr Phe Val Asn Asn Ile Gln Tyr Leu Asp Pro Arg 20 25 30 His Trp Gly Pro Ser Leu Phe Ala Thr Ile Ser Gln Ala Leu Trp His 35 40 45 Val Ile Arg Asp Asp Ile Pro Ala Ile Thr Ser Gln Glu Leu Gln Arg 50 55 60 Arg Thr Glu Arg Phe Phe Arg Asp Ser Leu Ala Arg Phe Leu Glu Glu 65 70 75 80 Thr Thr Trp Thr Ile Val Asn Ala Pro Val Asn Phe Tyr Asn Tyr Ile 85 90 95 Gln Asp Tyr Tyr Ser Asn Leu Ser Pro Ile Arg Pro Ser Met Val Arg 100 105 110 Gln Val Ala Glu Arg Glu Gly Thr His Val Asn Phe Gly His Thr Tyr 115 120 125 Ser Ile Asp Asp Ala Asp Ser Ile Glu Glu Val Thr Gln Arg Ile Glu 130 135 140 Leu Arg Asn Lys Glu Ser Val His Ser Gly Glu Phe Ile Glu Lys Thr 145 150 155 160 Ile Ala Pro Gly Gly Ala Asn Gln Arg Thr Ala Pro Gln Trp Met Leu 165 170 175 Pro Leu Leu Leu Gly Leu Tyr Gly Thr Val Thr Pro Ala Leu Glu Ala 180 185 190 Tyr Glu Asp Gly Pro Asn Gln Lys Lys Arg Arg Val Ser Arg Gly Ser 195 200 205 Ser Gln Lys Ala Lys Gly Thr Arg Ala Ser Ala Lys Thr Thr Asn Lys 210 215 220 Arg Arg Ser Arg Ser Ser Arg Ser 225 230 10362PRTBK virus 10Met Ala Pro Thr Lys Arg Lys Gly Glu Cys Pro Gly Ala Ala Pro Lys 1 5 10 15 Lys Pro Lys Glu Pro Val Gln Val Pro Lys Leu Leu Ile Lys Gly Gly 20 25 30 Val Glu Val Leu Glu Val Lys Thr Gly Val Asp Ala Ile Thr Glu Val 35 40 45 Glu Cys Phe Leu Asn Pro Glu Met Gly Asp Pro Asp Asp His Leu Arg 50 55 60 Gly Tyr Ser Gln His Leu Thr Ala Glu Asn Ala Phe Asp Ser Asp Ser 65 70 75 80 Pro Asp Lys Lys Met Leu Pro Cys Tyr Ser Thr Ala Arg Ile Pro Leu 85 90 95 Pro Asn Leu Asn Glu Asp Leu Thr Cys Gly Asn Leu Leu Met Trp Glu 100 105 110 Ala Val Thr Val Lys Thr Glu Val Ile Gly Ile Thr Ser Met Leu Asn 115 120 125 Leu His Ala Gly Ser Gln Lys Val His Glu Asn Gly Gly Gly Lys Pro 130 135 140 Val Gln Gly Ser Asn Phe His Phe Phe Ala Val Gly Gly Asp Pro Leu 145 150 155 160 Glu Met Gln Gly Val Leu Met Asn Tyr Arg Thr Lys Tyr Pro Gln Gly 165 170 175 Thr Ile Thr Pro Lys Asn Pro Thr Ala Gln Ser Gln Val Met Asn Thr 180 185 190 Asp His Lys Ala Tyr Leu Asp Lys Asn Asn Ala Tyr Pro Val Glu Cys 195 200 205 Trp Ile Pro Asp Pro Ser Lys Asn Glu Asn Thr Arg Tyr Phe Gly Thr 210 215 220 Tyr Thr Gly Gly Glu Asn Val Pro Pro Val Leu His Val Thr Asn Thr 225 230 235 240 Ala Thr Thr Val Leu Leu Asp Glu Gln Gly Val Gly Pro Leu Cys Lys 245 250 255 Ala Asp Ser Leu Tyr Val Ser Ala Ala Asp Ile Cys Gly Leu Phe Thr 260 265 270 Asn Ser Ser Gly Thr Gln Gln Trp Arg Gly Leu Ala Arg Tyr Phe Lys 275 280 285 Ile Arg Leu Arg Lys Arg Ser Val Lys Asn Pro Tyr Pro Ile Ser Phe 290 295 300 Leu Leu Ser Asp Leu Ile Asn Arg Arg Thr Gln Lys Val Asp Gly Gln 305 310 315 320 Pro Met Tyr Gly Met Glu Ser Gln Val Glu Glu Val Arg Val Phe Asp 325 330 335 Gly Thr Glu Gln Leu Pro Gly Asp Pro Asp Met Ile Arg Tyr Ile Asp 340 345 350 Arg Gln Gly Gln Leu Gln Thr Lys Met Val 355 360 11351PRTBK virus 11Met Gly Ala Ala Leu Ala Leu Leu Gly Asp Leu Val Ala Ser Val Ser 1 5 10 15 Glu Ala Ala Ala Ala Thr Gly Phe Ser Val Ala Glu Ile Ala Ala Gly 20 25 30 Glu Ala Ala Ala Ala Ile Glu Val Gln Ile Ala Ser Leu Ala Thr Val 35 40 45 Glu Gly Ile Thr Thr Thr Ser Glu Ala Ile Ala Ala Ile Gly Leu Thr 50 55 60 Pro Gln Thr Tyr Ala Val Ile Ala Gly Ala Pro Gly Ala Ile Ala Gly 65 70 75 80 Phe Ala Ala Leu Ile Gln Thr Val Thr Gly Ile Ser Ser Leu Ala Gln 85 90 95 Val Gly Tyr Arg Phe Phe Ser Asp Trp Asp His Lys Val Ser Thr Val 100 105 110 Gly Leu Tyr Gln Gln Ser Gly Met Ala Leu Glu Leu Phe Asn Pro Asp 115 120 125 Glu Tyr Tyr Asp Ile Leu Phe Pro Gly Val Asn Thr Phe Val Asn Asn 130 135 140 Ile Gln Tyr Leu Asp Pro Arg His Trp Gly Pro Ser Leu Phe Ala Thr 145 150 155 160 Ile Ser Gln Ala Leu Trp His Val Ile Arg Asp Asp Ile Pro Ala Ile 165 170 175 Thr Ser Gln Glu Leu Gln Arg Arg Thr Glu Arg Phe Phe Arg Asp Ser 180 185 190 Leu Ala Arg Phe Leu Glu Glu Thr Thr Trp Thr Ile Val Asn Ala Pro 195 200 205 Ile Asn Phe Tyr Asn Tyr Ile Gln Asp Tyr Tyr Ser Asn Leu Ser Pro 210 215 220 Ile Arg Pro Ser Met Val Arg Gln Val Ala Glu Arg Glu Gly Thr His 225 230 235 240 Val Asn Phe Gly His Thr Tyr Ser Ile Asp Asn Ala Asp Ser Ile Glu 245 250 255 Glu Val Thr Gln Arg Met Asp Leu Arg Asn Lys Glu Ser Val His Ser 260 265 270 Gly Glu Phe Ile Glu Lys Thr Ile Ala Pro Gly Gly Ala Asn Gln Arg 275 280 285 Thr Ala Pro Gln Trp Met Leu Pro Leu Leu Leu Gly Leu Tyr Gly Thr 290 295 300 Val Thr Pro Ala Leu Glu Ala Tyr Glu Asp Gly Pro Asn Gln Lys Lys 305 310 315 320 Arg Arg Val Ser Arg Gly Ser Ser Gln Lys Ala Lys Gly Thr Arg Ala 325 330 335 Ser Ala Lys Thr Thr Asn Lys Arg Arg Ser Arg Ser Ser Arg Ser 340 345 350 12232PRTBK virus 12Met Ala Leu Glu Leu Phe Asn Pro Asp Glu Tyr Tyr Asp Ile Leu Phe 1 5 10 15 Pro Gly Val Asn Thr Phe Val Asn Asn Ile Gln Tyr Leu Asp Pro Arg 20 25 30 His Trp Gly Pro Ser Leu Phe Ala Thr Ile Ser Gln Ala Leu Trp His 35 40 45 Val Ile Arg Asp Asp Ile Pro Ala Ile Thr Ser Gln Glu Leu Gln Arg 50 55 60 Arg Thr Glu Arg Phe Phe Arg Asp Ser Leu Ala Arg Phe Leu Glu Glu 65 70 75 80 Thr Thr Trp Thr Ile Val Asn Ala Pro Ile Asn Phe Tyr Asn Tyr Ile 85 90 95 Gln Asp Tyr Tyr Ser Asn Leu Ser Pro Ile Arg Pro Ser Met Val Arg 100 105 110 Gln Val Ala Glu Arg Glu Gly Thr His Val Asn Phe Gly His Thr Tyr 115 120 125 Ser Ile Asp Asn Ala Asp Ser Ile Glu Glu Val Thr Gln Arg Met Asp 130 135 140 Leu Arg Asn Lys Glu Ser Val His Ser Gly Glu Phe Ile Glu Lys Thr 145 150 155 160 Ile Ala Pro Gly Gly Ala Asn Gln Arg Thr Ala Pro Gln Trp Met Leu 165 170 175 Pro Leu Leu Leu Gly Leu Tyr Gly Thr Val Thr Pro Ala Leu Glu Ala 180 185 190 Tyr Glu Asp Gly Pro Asn Gln Lys Lys Arg Arg Val Ser Arg Gly Ser 195 200 205 Ser Gln Lys Ala Lys Gly Thr Arg Ala Ser Ala Lys Thr Thr Asn Lys 210 215 220 Arg Arg Ser Arg Ser Ser Arg Ser 225 230 13362PRTBK virus 13Met Ala Pro Thr Lys Arg Lys Gly Glu Cys Pro Gly Ala Ala Pro Lys 1 5 10 15 Lys Pro Lys Glu Pro Val Gln Val Pro Lys Leu Leu Ile Lys Gly Gly 20 25 30 Val Glu Val Leu Glu Val Lys Thr Gly Val Asp Ala Ile Thr Glu Val 35 40 45 Glu Cys Phe Leu Asn Pro Glu Met Gly Asp Pro Asp Glu Asn Leu Arg 50 55 60 Gly Phe Ser Leu Lys Leu Ser Ala Glu Asn Asp Phe Ser Ser Asp Ser 65 70 75 80 Pro Glu Arg Lys Met Leu Pro Cys Tyr Ser Thr Ala Arg Ile Pro Leu 85 90 95 Pro Asn Leu Asn Glu Asp Leu Thr Cys Gly Asn Leu Leu Met Trp Glu 100 105 110 Ala Val Thr Val Gln Thr Glu Val Ile Gly Ile Thr Ser Met Leu Asn 115 120 125 Leu His Ala Gly Ser Gln Lys Val His Glu His Gly Gly Gly Lys Pro 130 135 140 Ile Gln Gly Ser Asn Phe His Phe Phe Ala Val Gly Gly Asp Pro Leu 145 150 155 160 Glu Met Gln Gly Val Leu Met Asn Tyr Arg Thr Lys Tyr Pro Asp Gly 165 170 175 Thr Ile Thr Pro Lys Asn Pro Thr Ala Gln Ser Gln Val Met Asn Thr 180 185 190 Asp His Lys Ala Tyr Leu Asp Lys Asn Asn Ala Tyr Pro Val Glu Cys 195 200 205 Trp Val Pro Asp Pro Ser Arg Asn Glu Asn Thr Arg Tyr Phe Gly Thr 210 215 220 Phe Thr Gly Gly Glu Asn Val Pro Pro Val Leu His Val Thr Asn Thr 225 230 235 240 Ala Thr Thr Val Leu Leu Asp Glu Gln Gly Val Gly Pro Leu Cys Lys 245 250 255 Ala Asp Ser Leu Tyr Val Ser Ala Ala Asp Ile Cys Gly Leu Phe Thr 260 265 270 Asn Ser Ser Gly Thr Gln Gln Trp Arg Gly Leu Ala Arg Tyr Phe Lys 275 280 285 Ile Arg Leu Arg Lys Arg Ser Val Lys Asn Pro Tyr Pro Ile Ser Phe 290 295 300 Leu Leu Ser Asp Leu Ile Asn Arg Arg Thr Gln Arg Val Asp Gly Gln 305 310 315 320 Pro Met Tyr Gly Met Glu Ser Gln Val Glu Glu Val Arg Val Phe Asp 325 330 335 Gly Thr Glu Arg Leu Pro Gly Asp Pro Asp Met Ile Arg Tyr Ile Asp 340 345 350 Lys Gln Gly Gln Leu Gln Thr Lys Met Leu 355 360 14362PRTBK virus 14Met Ala Pro Thr Lys Arg Lys Gly Glu Cys Pro Gly Ala Ala Pro Lys 1 5 10 15 Lys Pro Lys Glu Pro Val Gln Val Pro Lys Leu Leu Ile Lys Gly Gly 20 25 30 Val Glu Val Leu Glu Val Lys Thr Gly Leu Asp Ala Ile Thr Glu Val 35 40 45 Glu Cys Phe Leu Asn Pro Glu Met Gly Asp Pro Asp Glu Asn Leu Arg 50 55 60 Gly Phe Ser Leu Lys Leu Ser Ala Lys Asn Asp Phe Ser Ser Asp Ser 65 70 75 80 Pro Asp Arg Lys Met Leu Pro Cys Tyr Ser Thr Ala Arg Ile Pro Leu 85 90 95 Pro Asn Leu Asn Glu Asp Leu Thr Cys Gly Asn Leu Leu Met Trp Glu 100 105 110 Ala Val Thr Val Gln Thr Glu Val Ile Gly Ile Thr Ser Met Leu Asn 115 120 125 Leu His Ala Gly Ser Gln Lys Val His Glu His Gly Gly Gly Lys Pro 130 135 140 Ile Gln Gly Ser Asn Phe His Phe Phe Ala Val Gly Gly Asp Pro Leu 145 150 155 160 Glu Met Gln Gly Val Leu Met Asn Tyr Arg Thr Lys Tyr Pro Glu Gly 165 170 175 Thr Ile Thr Pro Lys Asn Pro Thr Ala Gln Ser Gln Val Met Asn Thr 180 185 190 Asp His Lys Ala Tyr Leu Asp Lys Asn Asn Ala Tyr Pro Val Glu Cys 195 200 205 Trp Ile Pro Asp Pro Ser Arg Asn Glu Asn Thr Arg Tyr Phe Gly Thr 210 215 220 Phe Thr Gly Gly Glu Asn Val Pro Pro Val Leu His Val Thr Asn Thr 225 230 235 240 Ala Thr Thr Val Leu Leu Asp Glu Gln Gly Val Gly Pro Leu Cys Lys 245 250 255 Ala Asp Ser Leu Tyr Val Ser Ala Ala Asp Ile Cys Gly Leu Phe Thr 260 265 270 Asn Ser Ser Gly Thr Gln Gln Trp Arg Gly Leu Ala Arg Tyr Phe Lys 275 280 285 Ile Arg Leu Arg Lys Arg Ser Val Lys Asn Pro Tyr Pro Ile Ser Phe 290 295 300 Leu Leu Ser Asp Leu Ile Asn Arg Arg Thr Gln Arg Val Asp Gly Gln 305 310 315 320 Pro Met Tyr Gly Met Glu Ser Gln Val Glu Glu Val Arg Val Phe Asp 325 330 335 Gly Thr Glu Arg Leu Pro Gly Asp Pro Asp Met Ile Arg Tyr Ile Asp 340 345 350 Lys Gln Gly Gln Leu Gln Thr Lys Met Leu 355 360 15362PRTBK virus 15Met Ala Pro Thr Lys Arg Lys Gly Glu Cys Pro Gly Ala Ala Pro Lys 1 5 10 15 Lys Pro Lys Glu Pro Val Gln Val Pro Lys Leu Leu Ile Lys Gly Gly 20 25 30 Val Glu Val Leu Glu Val Lys Thr Gly Val Asp Ala Ile Thr Glu Val 35 40 45 Glu Cys Phe Leu Asn Pro Glu Met Gly Asp Pro Asp Glu Asn Leu Arg 50 55 60 Gly Phe Ser Leu Lys Leu Ser Val Glu Asn Asp Phe Ser

Ser Asp Ser 65 70 75 80 Pro Gln Arg Lys Met Leu Pro Cys Tyr Ser Thr Ala Arg Ile Pro Leu 85 90 95 Pro Asn Leu Asn Glu Asp Leu Thr Cys Gly Asn Leu Leu Met Trp Glu 100 105 110 Ala Val Thr Val Gln Thr Glu Val Ile Gly Ile Thr Ser Met Leu Asn 115 120 125 Leu His Ala Gly Ser Gln Lys Val His Glu His Gly Gly Gly Lys Pro 130 135 140 Ile Gln Gly Ser Asn Phe His Phe Phe Ala Val Gly Gly Asp Pro Leu 145 150 155 160 Glu Met Gln Gly Val Leu Met Asn Tyr Arg Thr Lys Tyr Pro Glu Gly 165 170 175 Thr Ile Thr Pro Lys Asn Pro Thr Ala Gln Ser Gln Val Met Asn Thr 180 185 190 Asp His Lys Ala Tyr Leu Asp Lys Asn Asn Ala Tyr Pro Val Glu Cys 195 200 205 Trp Ile Pro Asp Pro Ser Arg Asn Glu Asn Thr Arg Tyr Phe Gly Thr 210 215 220 Leu Thr Gly Gly Glu Asn Val Pro Pro Val Leu His Val Thr Asn Thr 225 230 235 240 Ala Thr Thr Val Leu Leu Asp Glu Gln Gly Val Gly Pro Leu Cys Lys 245 250 255 Ala Asp Ser Leu Tyr Val Ser Ala Ala Asp Ile Cys Gly Leu Phe Thr 260 265 270 Asn Ser Ser Gly Thr Gln Gln Trp Arg Gly Leu Ala Arg Tyr Phe Lys 275 280 285 Ile Arg Leu Arg Lys Arg Ser Val Lys Asn Pro Tyr Pro Ile Ser Phe 290 295 300 Leu Leu Ser Asp Leu Ile Asn Arg Arg Thr Gln Arg Val Asp Gly Gln 305 310 315 320 Pro Met Tyr Gly Met Glu Ser Gln Val Glu Glu Val Arg Val Phe Asp 325 330 335 Gly Thr Glu Lys Leu Pro Gly Asp Pro Asp Met Ile Arg Tyr Ile Asp 340 345 350 Lys Gln Gly Gln Leu Gln Thr Lys Met Leu 355 360 16362PRTBK virus 16Met Ala Pro Thr Lys Arg Lys Gly Glu Cys Pro Gly Ala Ala Pro Lys 1 5 10 15 Lys Pro Lys Glu Pro Val Gln Val Pro Lys Leu Leu Ile Lys Gly Gly 20 25 30 Val Glu Val Leu Glu Val Lys Thr Gly Val Asp Ala Ile Thr Glu Val 35 40 45 Glu Cys Phe Leu Asn Pro Glu Met Gly Asp Pro Asp Asn Asp Leu Arg 50 55 60 Gly Tyr Ser Leu Arg Leu Thr Ala Glu Thr Ala Phe Asn Ser Asp Ser 65 70 75 80 Pro Asp Arg Lys Met Leu Pro Cys Tyr Ser Thr Ala Arg Ile Pro Leu 85 90 95 Pro Asn Leu Asn Glu Asp Leu Thr Cys Gly Asn Leu Leu Met Trp Glu 100 105 110 Ala Val Thr Val Lys Thr Glu Val Ile Gly Ile Thr Ser Met Leu Asn 115 120 125 Leu His Ala Gly Ser Gln Lys Val His Asp Asn Gly Gly Gly Lys Pro 130 135 140 Ile Gln Gly Ser Asn Phe His Phe Phe Ala Val Gly Gly Asp Pro Leu 145 150 155 160 Glu Met Gln Gly Val Leu Met Asn Tyr Arg Thr Lys Tyr Pro Glu Gly 165 170 175 Thr Val Thr Pro Lys Asn Pro Thr Ala Gln Ser Gln Val Met Asn Thr 180 185 190 Asp His Lys Ala Tyr Leu Asp Lys Asn Asn Ala Tyr Pro Val Glu Cys 195 200 205 Trp Ile Pro Asp Pro Ser Arg Asn Glu Asn Thr Arg Tyr Phe Gly Thr 210 215 220 Tyr Thr Gly Gly Glu Asn Val Pro Pro Val Leu His Val Thr Asn Thr 225 230 235 240 Ala Thr Thr Val Leu Leu Asp Glu Gln Gly Val Gly Pro Leu Cys Lys 245 250 255 Ala Asp Ser Leu Tyr Val Ser Ala Ala Asp Ile Cys Gly Leu Phe Thr 260 265 270 Asn Ser Ser Gly Thr Gln Gln Trp Arg Gly Leu Pro Arg Tyr Phe Lys 275 280 285 Ile Arg Leu Arg Lys Arg Ser Val Lys Asn Pro Tyr Pro Ile Ser Phe 290 295 300 Leu Leu Ser Asp Leu Ile Asn Arg Arg Thr Gln Arg Val Asp Gly Gln 305 310 315 320 Pro Met Tyr Gly Met Glu Ser Gln Val Glu Glu Val Arg Val Phe Asp 325 330 335 Gly Thr Glu Lys Leu Pro Gly Asp Pro Asp Met Ile Arg Tyr Ile Asp 340 345 350 Arg Gln Gly Gln Leu Gln Thr Lys Met Val 355 360 17354PRTJC virus 17Met Ala Pro Thr Lys Arg Lys Gly Glu Arg Lys Asp Pro Val Gln Val 1 5 10 15 Pro Lys Leu Leu Ile Arg Gly Gly Val Glu Val Leu Glu Val Lys Thr 20 25 30 Gly Val Asp Ser Ile Thr Glu Val Glu Cys Phe Leu Thr Pro Glu Met 35 40 45 Gly Asp Pro Asp Glu His Leu Arg Gly Phe Ser Lys Ser Ile Ser Ile 50 55 60 Ser Asp Thr Phe Glu Ser Asp Ser Pro Asn Arg Asp Met Leu Pro Cys 65 70 75 80 Tyr Ser Val Ala Arg Ile Pro Leu Pro Asn Leu Asn Glu Asp Leu Thr 85 90 95 Cys Gly Asn Ile Leu Met Trp Glu Ala Val Thr Leu Lys Thr Glu Val 100 105 110 Ile Gly Val Thr Ser Leu Met Asn Val His Ser Asn Gly Gln Ala Thr 115 120 125 His Asp Asn Gly Ala Gly Lys Pro Val Gln Gly Thr Ser Phe His Phe 130 135 140 Phe Ser Val Gly Gly Glu Ala Leu Glu Leu Gln Gly Val Leu Phe Asn 145 150 155 160 Tyr Arg Thr Lys Tyr Pro Asp Gly Thr Ile Phe Pro Lys Asn Ala Thr 165 170 175 Val Gln Ser Gln Val Met Asn Thr Glu His Lys Ala Tyr Leu Asp Lys 180 185 190 Asn Lys Ala Tyr Pro Val Glu Cys Trp Val Pro Asp Pro Thr Arg Asn 195 200 205 Glu Asn Thr Arg Tyr Phe Gly Thr Leu Thr Gly Gly Glu Asn Val Pro 210 215 220 Pro Val Leu His Ile Thr Asn Thr Ala Thr Thr Val Leu Leu Asp Glu 225 230 235 240 Phe Gly Val Gly Pro Leu Cys Lys Gly Asp Asn Leu Tyr Leu Ser Ala 245 250 255 Val Asp Val Cys Gly Met Phe Thr Asn Arg Ser Gly Ser Gln Gln Trp 260 265 270 Arg Gly Leu Ser Arg Tyr Phe Lys Val Gln Leu Arg Lys Arg Arg Val 275 280 285 Lys Asn Pro Tyr Pro Ile Ser Phe Leu Leu Thr Asp Leu Ile Asn Arg 290 295 300 Arg Thr Pro Arg Val Asp Gly Gln Pro Met Tyr Gly Met Asp Ala Gln 305 310 315 320 Val Glu Glu Val Arg Val Phe Glu Gly Thr Glu Glu Leu Pro Gly Asp 325 330 335 Pro Asp Met Met Arg Tyr Val Asp Lys Tyr Gly Gln Leu Gln Thr Lys 340 345 350 Met Leu 18344PRTJC virus 18Met Gly Ala Ala Leu Ala Leu Leu Gly Asp Leu Val Ala Thr Val Ser 1 5 10 15 Glu Ala Ala Ala Ala Thr Gly Phe Ser Val Ala Glu Ile Ala Ala Gly 20 25 30 Glu Ala Ala Ala Thr Ile Glu Val Glu Ile Ala Ser Leu Ala Thr Val 35 40 45 Glu Gly Ile Thr Ser Thr Ser Glu Ala Ile Ala Ala Ile Gly Leu Thr 50 55 60 Pro Glu Thr Tyr Ala Val Ile Thr Gly Ala Pro Gly Ala Val Ala Gly 65 70 75 80 Phe Ala Ala Leu Val Gln Thr Val Thr Gly Gly Ser Ala Ile Ala Gln 85 90 95 Leu Gly Tyr Arg Phe Phe Ala Asp Trp Asp His Lys Val Ser Thr Val 100 105 110 Gly Leu Phe Gln Gln Pro Ala Met Ala Leu Gln Leu Phe Asn Pro Glu 115 120 125 Asp Tyr Tyr Asp Ile Leu Phe Pro Gly Val Asn Ala Phe Val Asn Asn 130 135 140 Ile His Tyr Leu Asp Pro Arg His Trp Gly Pro Ser Leu Phe Ser Thr 145 150 155 160 Ile Ser Gln Ala Phe Trp Asn Leu Val Arg Asp Asp Leu Pro Ala Leu 165 170 175 Thr Ser Gln Glu Ile Gln Arg Arg Thr Gln Lys Leu Phe Val Glu Ser 180 185 190 Leu Ala Arg Phe Leu Glu Glu Thr Thr Trp Ala Ile Val Asn Ser Pro 195 200 205 Ala Asn Leu Tyr Asn Tyr Ile Ser Asp Tyr Tyr Ser Arg Leu Ser Pro 210 215 220 Val Arg Pro Ser Met Val Arg Gln Val Ala Gln Arg Glu Gly Thr Tyr 225 230 235 240 Ile Ser Phe Gly His Ser Tyr Thr Gln Ser Ile Asp Asp Ala Asp Ser 245 250 255 Ile Gln Glu Val Thr Gln Arg Leu Asp Leu Lys Thr Pro Asn Val Gln 260 265 270 Ser Gly Glu Phe Ile Glu Arg Ser Ile Ala Pro Gly Gly Ala Asn Gln 275 280 285 Arg Ser Ala Pro Gln Trp Met Leu Pro Leu Leu Leu Gly Leu Tyr Gly 290 295 300 Thr Val Thr Pro Ala Leu Glu Ala Tyr Glu Asp Gly Pro Asn Lys Lys 305 310 315 320 Lys Arg Arg Lys Glu Gly Pro Arg Ala Ser Ser Lys Thr Ser Tyr Lys 325 330 335 Arg Arg Ser Arg Ser Ser Arg Ser 340 19225PRTJC virus 19Met Ala Leu Gln Leu Phe Asn Pro Glu Asp Tyr Tyr Asp Ile Leu Phe 1 5 10 15 Pro Gly Val Asn Ala Phe Val Asn Asn Ile His Tyr Leu Asp Pro Arg 20 25 30 His Trp Gly Pro Ser Leu Phe Ser Thr Ile Ser Gln Ala Phe Trp Asn 35 40 45 Leu Val Arg Asp Asp Leu Pro Ala Leu Thr Ser Gln Glu Ile Gln Arg 50 55 60 Arg Thr Gln Lys Leu Phe Val Glu Ser Leu Ala Arg Phe Leu Glu Glu 65 70 75 80 Thr Thr Trp Ala Ile Val Asn Ser Pro Ala Asn Leu Tyr Asn Tyr Ile 85 90 95 Ser Asp Tyr Tyr Ser Arg Leu Ser Pro Val Arg Pro Ser Met Val Arg 100 105 110 Gln Val Ala Gln Arg Glu Gly Thr Tyr Ile Ser Phe Gly His Ser Tyr 115 120 125 Thr Gln Ser Ile Asp Asp Ala Asp Ser Ile Gln Glu Val Thr Gln Arg 130 135 140 Leu Asp Leu Lys Thr Pro Asn Val Gln Ser Gly Glu Phe Ile Glu Arg 145 150 155 160 Ser Ile Ala Pro Gly Gly Ala Asn Gln Arg Ser Ala Pro Gln Trp Met 165 170 175 Leu Pro Leu Leu Leu Gly Leu Tyr Gly Thr Val Thr Pro Ala Leu Glu 180 185 190 Ala Tyr Glu Asp Gly Pro Asn Lys Lys Lys Arg Arg Lys Glu Gly Pro 195 200 205 Arg Ala Ser Ser Lys Thr Ser Tyr Lys Arg Arg Ser Arg Ser Ser Arg 210 215 220 Ser 225 20354PRTJC virus 20Met Ala Pro Thr Lys Arg Lys Gly Glu Arg Lys Asp Pro Val Gln Val 1 5 10 15 Pro Lys Leu Leu Ile Arg Gly Gly Val Glu Val Leu Glu Val Lys Thr 20 25 30 Gly Val Asp Ser Ile Thr Glu Val Glu Cys Phe Leu Thr Pro Glu Met 35 40 45 Gly Asp Pro Asp Glu His Leu Arg Gly Phe Ser Lys Ser Ile Ser Ile 50 55 60 Ser Asp Thr Phe Glu Ser Asp Ser Pro Asn Lys Asp Met Leu Pro Cys 65 70 75 80 Tyr Ser Val Ala Arg Ile Pro Leu Pro Asn Leu Asn Glu Asp Leu Thr 85 90 95 Cys Gly Asn Ile Leu Met Trp Glu Ala Val Thr Leu Lys Thr Glu Val 100 105 110 Ile Gly Val Thr Thr Leu Met Asn Val His Ser Asn Gly Gln Ala Thr 115 120 125 His Asp Asn Gly Ala Gly Lys Pro Val Gln Gly Thr Ser Phe His Phe 130 135 140 Phe Ser Val Gly Gly Glu Ala Leu Glu Leu Gln Gly Val Val Phe Asn 145 150 155 160 Tyr Arg Thr Lys Tyr Pro Asp Gly Thr Ile Phe Pro Lys Asn Ala Thr 165 170 175 Val Gln Ser Gln Val Met Asn Thr Glu His Lys Ala Tyr Leu Asp Lys 180 185 190 Asn Lys Ala Tyr Pro Val Glu Cys Trp Val Pro Asp Pro Thr Arg Asn 195 200 205 Glu Asn Thr Arg Tyr Phe Gly Thr Leu Thr Gly Gly Glu Asn Val Pro 210 215 220 Pro Val Leu His Ile Thr Asn Thr Ala Thr Thr Val Leu Leu Asp Glu 225 230 235 240 Phe Gly Val Gly Pro Leu Cys Lys Gly Asp Asn Leu Tyr Leu Ser Ala 245 250 255 Val Asp Val Cys Gly Met Phe Thr Asn Arg Ser Gly Ser Gln Gln Trp 260 265 270 Arg Gly Leu Ser Arg Tyr Phe Lys Val Gln Leu Arg Lys Arg Arg Val 275 280 285 Lys Asn Pro Tyr Pro Ile Ser Phe Leu Leu Thr Asp Leu Ile Asn Arg 290 295 300 Arg Thr Pro Arg Val Asp Gly Gln Pro Met Tyr Gly Met Asp Ala Gln 305 310 315 320 Val Glu Glu Val Arg Val Phe Glu Gly Thr Glu Glu Leu Pro Gly Asp 325 330 335 Pro Asp Met Met Arg Tyr Val Asp Arg Tyr Gly Gln Leu Gln Thr Lys 340 345 350 Met Leu 21354PRTJC virus 21Met Ala Pro Thr Lys Arg Lys Gly Glu Arg Lys Asp Pro Val Gln Val 1 5 10 15 Pro Lys Leu Leu Ile Arg Gly Gly Val Glu Val Leu Glu Val Lys Thr 20 25 30 Gly Val Asp Ser Ile Thr Glu Val Glu Cys Phe Leu Thr Pro Glu Met 35 40 45 Gly Asp Pro Asp Glu His Phe Arg Gly Phe Ser Lys Ser Ile Ser Ile 50 55 60 Ser Asp Thr Phe Glu Ser Asp Ser Pro Asn Lys Asp Met Leu Pro Cys 65 70 75 80 Tyr Ser Val Ala Arg Ile Pro Leu Pro Asn Leu Asn Glu Asp Leu Thr 85 90 95 Cys Gly Asn Ile Leu Met Trp Glu Ala Val Thr Leu Lys Thr Glu Val 100 105 110 Ile Gly Val Thr Thr Leu Met Asn Val His Ser Asn Gly Gln Ala Thr 115 120 125 His Asp Asn Gly Ala Ala Lys Pro Val Gln Gly Thr Ser Phe His Phe 130 135 140 Phe Ser Val Gly Gly Glu Ala Leu Glu Leu Gln Gly Val Val Phe Asn 145 150 155 160 Tyr Arg Thr Thr Tyr Pro Asp Gly Thr Ile Phe Pro Lys Asn Ala Thr 165 170 175 Val Gln Ser Gln Val Met Asn Thr Glu His Lys Ala Tyr Leu Asp Lys 180 185 190 Asn Lys Ala Tyr Pro Val Glu Cys Trp Val Pro Asp Pro Thr Arg Asn 195 200 205 Glu Asn Thr Arg Tyr Phe Gly Thr Leu Thr Gly Gly Glu Asn Val Pro 210 215 220 Pro Val Leu His Ile Thr Asn Thr Ala Thr Thr Val Leu Leu Asp Glu 225 230 235 240 Phe Gly Val Gly Pro Leu Cys Lys Gly Asp Asn Leu Tyr Leu Ser Ala 245 250 255 Val Asp Val Cys Gly Met Phe Thr Asn Arg Ser Gly Ser Gln Gln Trp 260 265 270 Arg Gly Leu Ser Arg Tyr Phe Lys Val Gln Leu Arg Lys Arg Arg Val 275 280 285 Lys Asn Pro Tyr Pro Ile Ser Phe Leu Leu Thr Asp Leu Ile Asn Arg 290 295 300 Arg Thr Pro Arg Val Asp Gly Gln Pro Met Tyr Gly Met Asp Ala Gln 305 310 315 320 Ile Glu Glu Val Arg Val Phe Glu Gly Thr Glu Gln Leu Pro Gly Asp 325 330 335 Pro Asp Met Met Arg Tyr Val Asp Arg Tyr Gly Gln Leu Gln Thr Lys 340 345 350 Met Leu 22344PRTJC virus 22Met Gly Ala Ala Leu Ala Leu Leu Gly Asp Leu Val Ala Thr Val Ser 1

5 10 15 Glu Ala Ala Ala Ala Thr Gly Phe Ser Val Ala Glu Ile Ala Ala Gly 20 25 30 Glu Ala Ala Ala Thr Ile Glu Val Glu Ile Ala Ser Leu Ala Thr Val 35 40 45 Glu Gly Ile Thr Ser Thr Ser Glu Ala Ile Ala Ala Ile Gly Leu Thr 50 55 60 Pro Glu Thr Tyr Ala Val Ile Thr Gly Ala Pro Gly Ala Val Ala Gly 65 70 75 80 Phe Ala Ala Leu Val Gln Thr Val Thr Gly Gly Ser Ala Ile Ala Gln 85 90 95 Leu Gly Tyr Arg Phe Phe Ala Asp Trp Asp His Lys Val Ser Thr Val 100 105 110 Gly Leu Phe Gln Gln Pro Ala Met Ala Leu Gln Leu Phe Asn Pro Glu 115 120 125 Asp Tyr Tyr Asp Ile Leu Phe Pro Gly Val Asn Ala Phe Val Asn Asn 130 135 140 Ile His Tyr Leu Asp Pro Arg His Trp Gly Pro Ser Leu Phe Ser Thr 145 150 155 160 Ile Ser Gln Ala Phe Trp Asn Leu Val Arg Asp Asp Leu Pro Ser Leu 165 170 175 Thr Ser Gln Glu Ile Gln Arg Arg Thr Gln Lys Leu Phe Val Glu Ser 180 185 190 Leu Ala Arg Phe Leu Glu Glu Thr Thr Trp Ala Ile Val Asn Ser Pro 195 200 205 Val Asn Leu Tyr Asn Tyr Ile Ser Asp Tyr Tyr Ser Arg Leu Ser Pro 210 215 220 Val Arg Pro Ser Met Val Arg Gln Val Ala Gln Arg Glu Gly Thr Tyr 225 230 235 240 Ile Ser Phe Gly His Ser Tyr Thr Gln Ser Ile Asp Asp Ala Asp Ser 245 250 255 Ile Gln Glu Val Thr Gln Arg Leu Asp Leu Lys Thr Pro Asn Val Gln 260 265 270 Ser Gly Glu Phe Ile Glu Lys Ser Ile Ala Pro Gly Gly Ala Asn Gln 275 280 285 Arg Ser Ala Pro Gln Trp Met Leu Pro Leu Leu Leu Gly Leu Tyr Gly 290 295 300 Thr Val Thr Pro Ala Leu Glu Ala Tyr Glu Asp Gly Pro Asn Lys Lys 305 310 315 320 Lys Arg Arg Lys Glu Gly Pro Arg Ala Ser Ser Lys Thr Ser Tyr Lys 325 330 335 Arg Arg Ser Arg Ser Ser Arg Ser 340 23225PRTJC virus 23Met Ala Leu Gln Leu Phe Asn Pro Glu Asp Tyr Tyr Asp Ile Leu Phe 1 5 10 15 Pro Gly Val Asn Ala Phe Val Asn Asn Ile His Tyr Leu Asp Pro Arg 20 25 30 His Trp Gly Pro Ser Leu Phe Ser Thr Ile Ser Gln Ala Phe Trp Asn 35 40 45 Leu Val Arg Asp Asp Leu Pro Ser Leu Thr Ser Gln Glu Ile Gln Arg 50 55 60 Arg Thr Gln Lys Leu Phe Val Glu Ser Leu Ala Arg Phe Leu Glu Glu 65 70 75 80 Thr Thr Trp Ala Ile Val Asn Ser Pro Val Asn Leu Tyr Asn Tyr Ile 85 90 95 Ser Asp Tyr Tyr Ser Arg Leu Ser Pro Val Arg Pro Ser Met Val Arg 100 105 110 Gln Val Ala Gln Arg Glu Gly Thr Tyr Ile Ser Phe Gly His Ser Tyr 115 120 125 Thr Gln Ser Ile Asp Asp Ala Asp Ser Ile Gln Glu Val Thr Gln Arg 130 135 140 Leu Asp Leu Lys Thr Pro Asn Val Gln Ser Gly Glu Phe Ile Glu Lys 145 150 155 160 Ser Ile Ala Pro Gly Gly Ala Asn Gln Arg Ser Ala Pro Gln Trp Met 165 170 175 Leu Pro Leu Leu Leu Gly Leu Tyr Gly Thr Val Thr Pro Ala Leu Glu 180 185 190 Ala Tyr Glu Asp Gly Pro Asn Lys Lys Lys Arg Arg Lys Glu Gly Pro 195 200 205 Arg Ala Ser Ser Lys Thr Ser Tyr Lys Arg Arg Ser Arg Ser Ser Arg 210 215 220 Ser 225 241089DNABK virus 24atggccccaa ccaaaagaaa aggagagtgt ccaggggcag ctcccaaaaa gccaaaggaa 60cccgtgcaag tgccaaaact actaataaaa ggaggagtag aagttctaga agttaaaact 120ggggtagatg ctataacaga ggtagaatgc ttcctaaacc cagaaatggg ggatccagat 180gaaaacctta ggggctttag tctaaagcta agtgctgaaa atgactttag cagtgatagc 240ccagaaagaa aaatgcttcc ctgttacagc acagcaagaa ttcccctccc caatttaaat 300gaggacctaa cctgtggaaa tctactgatg tgggaggctg taactgtaca aacagaggtc 360attggaataa ctagcatgct taaccttcat gcagggtcac aaaaagtgca tgagcatggt 420ggaggtaaac ctattcaagg cagtaatttc cacttctttg ctgttggtgg agaccccttg 480gaaatgcagg gagtgctaat gaattacagg accaagtacc cagatggtac tataacccca 540aaaaacccaa cagcccagtc ccaggtaatg aatactgacc ataaggccta tttggacaaa 600aacaatgctt atccagttga gtgctgggtt cctgatccta gtagaaatga aaatactagg 660tattttggga ctttcacagg aggggaaaat gttcccccag tacttcatgt gaccaacaca 720gctaccacag tgttgctaga tgaacagggt gtggggcctc tttgtaaagc tgatagcctg 780tatgtttcag ctgctgatat ttgtggcctg tttactaaca gctctggaac acaacagtgg 840agaggccttg caagatattt taagattcgc ctgagaaaaa gatctgtaaa aaatccttac 900ccaatttcct ttttgctaag tgaccttata aacaggagaa cccagagagt ggatgggcag 960cctatgtatg gtatggaatc ccaggtagaa gaggttaggg tgtttgatgg cacagaaaga 1020cttccagggg acccagatat gataagatat attgataaac aaggacaatt gcaaaccaaa 1080atgctttaa 1089251056DNABK virus 25atgggtgctg ctctagcact tttgggggac ctagttgcca gtgtatctga ggctgctgct 60gccacaggat tttcagtggc tgaaattgct gctggggagg ctgctgctgc tatagaagtt 120caaattgcat cccttgctac tgtagagggc ataacaagta cctcagaggc tatagctgct 180ataggcctaa ctcctcaaac atatgctgta attgctggtg ctcctggggc tattgctggg 240tttgctgctt taattcaaac tgttactggt attagttcct tggctcaagt agggtatagg 300ttttttagtg attgggatca caaagtttcc actgtaggcc tctatcagca atcaggcatg 360gctttggaat tgtttaaccc agatgagtac tatgatattt tgtttcctgg tgtaaatact 420tttgtaaata atattcaata ccttgatcct aggcattggg gtccttcctt gtttgctact 480atttcccagg ctttgtggca tgttattagg gatgatatac ctgctataac ctcacaagaa 540ttgcaaagaa gaacagaaag attttttaga gactccttgg ctagattttt ggaggaaact 600acctggacaa ttgtaaatgc ccctataaac ttttataatt atattcaaga atattattct 660gatctttccc ctattaggcc ctcaatggtt agacaagtgg ctgaaaggga aggtacccgt 720gtacattttg gccatactta tagtatagat gatgctgaca gtatagaaga agttacacaa 780agaatggact taagaaatca acaaactgta cattcaggag agtttataga aaaaactatt 840gccccaggag gtgctaatca aagaactgct cctcaatgga tgttgccttt acttctaggc 900ctgtacggga ctgtaacacc tgctcttgaa gcatatgaag atggccccaa ccaaaagaaa 960aggagagtgt ccaggggcag ctcccaaaaa gccaaaggaa cccgtgcaag tgccaaaact 1020actaataaaa ggaggagtag aagttctaga agttaa 105626699DNABK virus 26atggctttgg aattgtttaa cccagatgag tactatgata ttttgtttcc tggtgtaaat 60acttttgtaa ataatattca ataccttgat cctaggcatt ggggtccttc cttgtttgct 120actatttccc aggctttgtg gcatgttatt agggatgata tacctgctat aacctcacaa 180gaattgcaaa gaagaacaga aagatttttt agagactcct tggctagatt tttggaggaa 240actacctgga caattgtaaa tgcccctata aacttttata attatattca agaatattat 300tctgatcttt cccctattag gccctcaatg gttagacaag tggctgaaag ggaaggtacc 360cgtgtacatt ttggccatac ttatagtata gatgatgctg acagtataga agaagttaca 420caaagaatgg acttaagaaa tcaacaaact gtacattcag gagagtttat agaaaaaact 480attgccccag gaggtgctaa tcaaagaact gctcctcaat ggatgttgcc tttacttcta 540ggcctgtacg ggactgtaac acctgctctt gaagcatatg aagatggccc caaccaaaag 600aaaaggagag tgtccagggg cagctcccaa aaagccaaag gaacccgtgc aagtgccaaa 660actactaata aaaggaggag tagaagttct agaagttaa 699271089DNABK virus 27atggccccaa ccaaaagaaa aggagagtgt ccaggggcag ctcccaaaaa gccaaaggaa 60cccgtgcaag tgccaaaact actaataaaa ggaggagtag aagttctaga agttaaaact 120ggggtagatg ctataacaga agtagaatgc tttctaaatc cagaaatggg ggatccagat 180aatgacctta ggggctatag tctaagacta actgctgaaa ctgcctttga cagtgatagc 240ccagacagaa aaatgcttcc ctgttacagc acagcaagaa ttccactacc taatttgaat 300gaggatctaa cctgtggaaa tctactaatg tgggaggctg tgactgtaaa aacagaggtt 360attggaataa ctagtatgct taaccttcat gcagggtcac agaaagtaca tgaaaatggt 420ggaggcaaac ctattcaagg cagcaatttt cacttttttg ctgtgggtgg ggaccccttg 480gaaatgcagg gagtacttat gaactacaga acaaagtacc cagaaggtac tgtcacccca 540aaaaatccca cagctcagtc ccaggtaatg aatactgacc ataaggccta cttggacaaa 600aacaatgctt atccagttga atgctggatt cctgacccta gtaaaaatga aaatactaga 660tattttggaa catacacagg aggggaaaat gttcccccag tacttcatgt aaccaacaca 720gctaccacag tgttgctgga tgaacagggt gtggggcctc tgtgtaaagc tgatagcctg 780tatgtttcag ctgctgatat ttgtggactg tttactaaca gctctggaac acaacagtgg 840aggggccttc caagatattt taagattcgc ctgagaaaaa gatctgtaaa gaacccttac 900ccaatttcct ttttgcttag tgaccttata aacaggagaa cccagagagt ggatgggcag 960cctatgtatg gtatggagtc tcaggtggag gaggtcaggg tgtttgatgg cacagaacag 1020cttccagggg acccagatat gataagatat attgacagac agggacaatt gcaaacaaaa 1080atggtttaa 1089281056DNABK virus 28atgggtgctg ctctagcact tttgggggac ctagttgcca gtgtatctga ggctgctgct 60gccacaggat tttcagtggc tgaaattgct gctggggagg ctgctgctgc tatagaagtt 120caaattgcat cccttgctac tgtagagggc ataacaagta cctcagaggc tatagctgct 180ataggcctaa ctcctcaaac atatgctgta attgctggtg ctccaggggc tattgctggg 240tttgctgctt taattcaaac tgttactggt attagttctt tggctcaagt agggtatagg 300ttttttagtg attgggatca caaagtttcc actgtaggcc tttatcagca atcaggcatg 360gcattggaat tgtttaaccc agatgagtac tatgatattt tgtttcctgg tgtaaatact 420tttgtaaata atattcaata cctagatcct aggcattggg gtccttcttt gtttgctact 480atttcccagg ctttgtggca tgttattagg gatgatatac ctgctataac ttcacaagaa 540ttgcaaagaa gaacagagag attctttaga gactccttgg ctagattttt ggaagaaact 600acctggacaa ttgtaaatgc ccctgtaaac ttttataatt atattcagga ttattattct 660aatttgtccc ctattaggcc ttcaatggtt aggcaagttg ctgaaaggga aggaacccag 720gtaaattttg gccataccta cagaatagat gatgctgaca gtatacaaga agttacccaa 780agaatggagt taagaaataa agagaatgta cattcaggag agtttataga aaaaactatt 840gccccaggag gtgctaatca aagaactgct cctcaatgga tgttgccttt gcttctaggc 900ctgtacggga ctgtaacacc tgctcttgaa gcatatgaag atggccccaa ccaaaagaaa 960aggagagtgt ccaggggcag ctcccaaaaa gccaaaggaa cccgtgcaag tgccaaaact 1020actaataaaa ggaggagtag aagttctaga agttaa 105629699DNABK virus 29atggcattgg aattgtttaa cccagatgag tactatgata ttttgtttcc tggtgtaaat 60acttttgtaa ataatattca atacctagat cctaggcatt ggggtccttc tttgtttgct 120actatttccc aggctttgtg gcatgttatt agggatgata tacctgctat aacttcacaa 180gaattgcaaa gaagaacaga gagattcttt agagactcct tggctagatt tttggaagaa 240actacctgga caattgtaaa tgcccctgta aacttttata attatattca ggattattat 300tctaatttgt cccctattag gccttcaatg gttaggcaag ttgctgaaag ggaaggaacc 360caggtaaatt ttggccatac ctacagaata gatgatgctg acagtataca agaagttacc 420caaagaatgg agttaagaaa taaagagaat gtacattcag gagagtttat agaaaaaact 480attgccccag gaggtgctaa tcaaagaact gctcctcaat ggatgttgcc tttgcttcta 540ggcctgtacg ggactgtaac acctgctctt gaagcatatg aagatggccc caaccaaaag 600aaaaggagag tgtccagggg cagctcccaa aaagccaaag gaacccgtgc aagtgccaaa 660actactaata aaaggaggag tagaagttct agaagttaa 699301089DNABK virus 30atggccccaa ccaaaagaaa aggagagtgt ccaggggcag ctcccaaaaa gccaaaggaa 60cccgtgcaag tgccaaaact actaataaaa ggaggagtag aagttctaga agttaaaact 120ggggtagatg ctataacaga ggtagaatgc tttctaaatc cagaaatggg ggatccagat 180aatgacctta ggggctatag tctaaagcta actgctgaaa atgcctttga cagtgatagc 240ccagacaaaa aaatgcttcc ttgttacagc acagcaagaa ttccactgcc caatctaaat 300gaggacctaa cctgtggaaa tctactaatg tgggaggctg taactgtaaa aacagaggtt 360attggaataa ctagcatgct taaccttcat gcagggtccc aaaaagttca tgagaatggt 420ggaggcaaac ctgtgcaagg cagtaatttc cacttctttg ctgtgggtgg agaccccttg 480gaaatgcagg gagtgctaat gaattacaga acaaagtacc cacaaggtac tataacccct 540aaaaacccta cagctcagtc ccaggtaatg aatactgatc ataaggccta tttggacaaa 600aacaatgctt atccagttga gtgctggatt cctgatccta gtagaaatga aaatactagg 660tattttggaa cttacacagg aggggaaaat gttcccccag tacttcatgt taccaacaca 720gctaccacag tgttgctgga tgaacagggt gtggggcctc tatgtaaagc tgacagcctg 780tatgtttcag ctgctgatat ttgtgggctg tttactaaca gctctgggac acaacagtgg 840agaggccttg caagatattt taagattcgc ctgagaaaaa gatctgtgaa gaatccttac 900ccaatttcct ttttgctaag tgaccttata aacaggagaa cccaaaaagt ggatgggcag 960cctatgtatg gtatggaatc tcaggttgag gaggtgaggg tgtttgatgg cacagaacag 1020cttccagggg acccagatat gataagatat attgacagac aaggacaatt gcaaacaaaa 1080atggtttaa 1089311056DNABK virus 31atgggtgctg ctctagcact tttgggggac ctagttgcca gtgtatctga ggctgctgct 60gccacaggat tttcagtggc tgaaattgct gctggggagg ctgctgctgc catagaagtt 120caaattgcat cccttgctac tgtagagggc ataacaacta cctcagaggc tatagctgct 180ataggcctaa cacctcaaac atatgctgta attgctggtg ctccaggggc tattgctggg 240tttgctgctt taattcaaac tgttactggt attagttctt tggctcaagt agggtatagg 300ttttttagtg attgggatca caaagtttcc actgtaggcc tttatcagca atcaggcatg 360gctttggaat tgtttaaccc agatgagtac tatgatattt tgtttcctgg tgtaaatact 420tttgtaaata atattcaata tctagatcct aggcattggg gtccttcttt gtttgctact 480atttctcagg ctttgtggca tgttattaga gatgatatac ctgctataac ttcacaagaa 540ttgcaaagga gaacagaaag attttttagg gactctttgg ctagattttt ggaagaaacc 600acctggacaa ttgtaaatgc ccctgtaaac ttttataatt atattcagga ttattattct 660aatttgtccc ctattaggcc ttcaatggtt aggcaagtag ctgaaaggga aggtacccat 720gtaaattttg gccataccta cagcatagat gatgctgaca gtatagaaga agttacccaa 780agaatagagt taagaaataa ggaaagtgta cattcaggag agtttataga aaaaactatt 840gccccaggag gtgctaatca aagaactgct cctcaatgga tgttgccttt gcttctaggc 900ctgtacggga ctgtaacacc tgctcttgaa gcatatgaag atggccccaa ccaaaagaaa 960aggagagtgt ccaggggcag ctcccaaaaa gccaaaggaa cccgtgcaag tgccaaaact 1020actaataaaa ggaggagtag aagttctaga agttaa 105632699DNABK virus 32atggctttgg aattgtttaa cccagatgag tactatgata ttttgtttcc tggtgtaaat 60acttttgtaa ataatattca atatctagat cctaggcatt ggggtccttc tttgtttgct 120actatttctc aggctttgtg gcatgttatt agagatgata tacctgctat aacttcacaa 180gaattgcaaa ggagaacaga aagatttttt agggactctt tggctagatt tttggaagaa 240accacctgga caattgtaaa tgcccctgta aacttttata attatattca ggattattat 300tctaatttgt cccctattag gccttcaatg gttaggcaag tagctgaaag ggaaggtacc 360catgtaaatt ttggccatac ctacagcata gatgatgctg acagtataga agaagttacc 420caaagaatag agttaagaaa taaggaaagt gtacattcag gagagtttat agaaaaaact 480attgccccag gaggtgctaa tcaaagaact gctcctcaat ggatgttgcc tttgcttcta 540ggcctgtacg ggactgtaac acctgctctt gaagcatatg aagatggccc caaccaaaag 600aaaaggagag tgtccagggg cagctcccaa aaagccaaag gaacccgtgc aagtgccaaa 660actactaata aaaggaggag tagaagttct agaagttaa 699331089DNABK virus 33atggccccaa ccaaaagaaa aggagagtgt ccaggggcag ctcccaaaaa gccaaaggaa 60cccgtgcaag tgccaaaact actaataaaa ggaggagtag aagttctaga agttaaaact 120ggggtagatg ctataacaga ggtagaatgc tttctaaacc cagaaatggg ggatccagat 180gatcacctta ggggctatag tcagcaccta actgctgaaa atgcctttga cagtgatagc 240ccagacaaaa aaatgcttcc ttgttacagt acagcaagaa ttccactgcc caacctaaat 300gaggacctaa cctgtggaaa tctactaatg tgggaggctg taactgtaaa aacagaggtt 360attggaataa ctagcatgct taaccttcat gcagggtccc aaaaagttca tgagaatggt 420ggaggtaaac ctgtccaagg cagtaatttc cacttctttg ctgtgggtgg agaccccttg 480gaaatgcagg gagtgctaat gaattacaga acaaagtacc cacaaggtac tataacccct 540aaaaacccta cagctcagtc ccaggtaatg aatactgatc ataaggccta tttggacaaa 600aacaatgctt atccagttga gtgctggatt cctgatccta gtaaaaatga aaatactagg 660tattttggaa cttacacagg aggggaaaat gttcctccag tacttcatgt taccaacaca 720gctaccacag tgttgctgga tgaacagggt gtggggcctc tgtgtaaagc tgatagcctg 780tatgtttcag ctgctgatat ttgtgggctg tttactaaca gctctgggac acaacagtgg 840agaggccttg caagatattt taagattcgc ctgagaaaaa gatctgtgaa gaatccttac 900ccaatttcct ttttgctaag tgaccttata aacaggagaa cccaaaaagt ggatgggcag 960cctatgtatg gtatggaatc tcaggttgag gaggtaaggg tgtttgatgg cacagaacag 1020cttccagggg acccagatat gataagatat attgacagac aaggacaatt gcaaacaaaa 1080atggtttaa 1089341056DNABK virus 34atgggtgctg ctctagcact tttgggggac ctagttgcca gtgtatctga ggctgctgct 60gccacaggat tttcagtggc tgaaattgct gctggggagg ctgctgctgc catagaagtt 120caaattgcat cccttgctac tgtagagggc ataacaacta cctcagaggc tatagctgct 180ataggcctaa cacctcaaac atatgctgta attgctggtg ctccaggggc tattgctggg 240tttgctgctt taattcaaac tgttactggt attagttctt tggctcaagt agggtatagg 300ttttttagtg attgggatca caaagtttcc actgtaggcc tttatcagca atcaggcatg 360gctttggaat tgtttaaccc agatgagtac tatgatattt tgtttcctgg tgtaaatacc 420tttgttaata atattcaata tctagatcct aggcattggg gtccttcttt gtttgctact 480atttcccagg ctttgtggca tgttattaga gatgatatac ctgctataac ttcacaagaa 540ttgcaaagga gaacagagag attttttagg gactctttgg ctagattttt ggaagaaacc 600acctggacaa ttgtaaatgc ccccataaac ttttataatt atattcagga ttattattct 660aatttgtccc ctattaggcc ttcaatggtt aggcaagtag ctgaaaggga aggtacccat 720gtaaattttg gccataccta cagcatagat aatgctgaca gtatagaaga agttacccaa 780agaatggatt taagaaataa ggaaagtgta cattcaggag agtttataga aaaaactatt 840gccccaggag gtgctaatca aagaactgct cctcaatgga tgttgccttt gcttctaggc 900ctgtacggga ctgtaacacc tgctcttgaa gcatatgaag atggccccaa ccaaaagaaa 960aggagagtgt ccaggggcag ctcccaaaaa gccaaaggaa cccgtgcaag tgccaaaact 1020actaataaaa ggaggagtag aagttctaga agttaa 105635699DNABK virus 35atggctttgg aattgtttaa cccagatgag tactatgata ttttgtttcc tggtgtaaat 60acctttgtta ataatattca atatctagat cctaggcatt ggggtccttc tttgtttgct

120actatttccc aggctttgtg gcatgttatt agagatgata tacctgctat aacttcacaa 180gaattgcaaa ggagaacaga gagatttttt agggactctt tggctagatt tttggaagaa 240accacctgga caattgtaaa tgcccccata aacttttata attatattca ggattattat 300tctaatttgt cccctattag gccttcaatg gttaggcaag tagctgaaag ggaaggtacc 360catgtaaatt ttggccatac ctacagcata gataatgctg acagtataga agaagttacc 420caaagaatgg atttaagaaa taaggaaagt gtacattcag gagagtttat agaaaaaact 480attgccccag gaggtgctaa tcaaagaact gctcctcaat ggatgttgcc tttgcttcta 540ggcctgtacg ggactgtaac acctgctctt gaagcatatg aagatggccc caaccaaaag 600aaaaggagag tgtccagggg cagctcccaa aaagccaaag gaacccgtgc aagtgccaaa 660actactaata aaaggaggag tagaagttct agaagttaa 699361065DNAJC virus 36atggccccaa caaaaagaaa aggagaaagg aaggaccccg tgcaagttcc aaaacttctt 60ataagaggag gagtagaagt tctagaagtt aaaactgggg ttgactcaat tacagaggta 120gaatgctttt taactccaga aatgggtgac ccagatgagc atcttagggg ttttagtaag 180tcaatatcta tatcagatac atttgaaagt gactccccaa atagggacat gcttccttgt 240tacagtgtgg ccagaattcc actacccaat ctaaatgagg atctaacctg tggaaatata 300ctcatgtggg aggctgtgac cttaaaaact gaggttatag gggtgacaag tttgatgaat 360gtgcactcta atgggcaagc aactcatgac aatggtgcag ggaagccagt gcagggcacc 420agctttcatt ttttttctgt tgggggggag gctttagaat tacagggggt gctttttaat 480tacagaacaa agtacccaga tggaacaatt tttccaaaga atgccacagt gcaatctcaa 540gtcatgaaca cagagcacaa ggcgtaccta gataagaaca aagcatatcc tgttgaatgt 600tgggttcctg atcccaccag aaatgaaaac acaagatatt ttgggacact aacaggagga 660gaaaatgttc ctccagttct tcatataaca aacactgcca caacagtgtt gcttgatgaa 720tttggtgttg ggccactttg caaaggtgac aacttatact tgtcagctgt tgatgtctgt 780ggcatgttta caaacaggtc tggttcccag cagtggagag gactctccag atattttaag 840gtgcagctaa ggaaaaggag ggttaaaaac ccctacccaa tttctttcct tcttactgat 900ttaattaaca gaaggactcc tagagttgat gggcagccta tgtatggcat ggatgctcaa 960gtagaggagg ttagagtttt tgagggaaca gaggagcttc caggggaccc agacatgatg 1020agatacgttg acaaatatgg acagttgcag acaaaaatgc tgtaa 1065371035DNAJC virus 37atgggtgccg cacttgcact tttgggggac ctagttgcta ctgtttctga ggctgctgct 60gccacaggat tttcagtagc tgaaattgct gctggagagg ctgctgctac tatagaagtt 120gaaattgcat cccttgctac tgtagagggg attacaagta cctctgaggc tatagctgct 180ataggcctta ctcctgaaac atatgctgta ataactggag ctccgggggc tgtagctggg 240tttgctgcat tggttcaaac tgtaactggt ggtagtgcta ttgctcagtt gggatataga 300ttttttgctg actgggatca taaagtttca acagttgggc tttttcagca gccagctatg 360gctttacaat tatttaatcc agaagactac tatgatattt tatttcctgg agtgaatgcc 420tttgttaaca atattcacta tttagatcct agacattggg gcccgtcctt gttctccaca 480atctcccagg ctttttggaa tcttgttaga gatgatttgc cagccttaac ctctcaggaa 540attcagagaa gaacccaaaa actatttgtt gaaagtttag caaggttttt ggaagaaact 600acttgggcaa tagttaattc accagctaac ttatataatt atatttcaga ctattattct 660agattgtctc cagttaggcc ctctatggta aggcaagttg cccaaaggga gggaacctat 720atttcttttg gccactcata cacccaaagt atagatgatg cagacagcat tcaagaagtt 780acccaaaggc tagatttaaa aaccccaaat gtgcaatctg gtgaatttat agaaagaagt 840attgcaccag gaggtgcaaa tcaaagatct gctcctcaat ggatgttgcc tttactttta 900gggttgtacg ggactgtaac acctgctctt gaagcatatg aagatggccc caacaaaaag 960aaaaggagaa aggaaggacc ccgtgcaagt tccaaaactt cttataagag gaggagtaga 1020agttctagaa gttaa 103538678DNAJC virus 38atggctttac aattatttaa tccagaagac tactatgata ttttatttcc tggagtgaat 60gcctttgtta acaatattca ctatttagat cctagacatt ggggcccgtc cttgttctcc 120acaatctccc aggctttttg gaatcttgtt agagatgatt tgccagcctt aacctctcag 180gaaattcaga gaagaaccca aaaactattt gttgaaagtt tagcaaggtt tttggaagaa 240actacttggg caatagttaa ttcaccagct aacttatata attatatttc agactattat 300tctagattgt ctccagttag gccctctatg gtaaggcaag ttgcccaaag ggagggaacc 360tatatttctt ttggccactc atacacccaa agtatagatg atgcagacag cattcaagaa 420gttacccaaa ggctagattt aaaaacccca aatgtgcaat ctggtgaatt tatagaaaga 480agtattgcac caggaggtgc aaatcaaaga tctgctcctc aatggatgtt gcctttactt 540ttagggttgt acgggactgt aacacctgct cttgaagcat atgaagatgg ccccaacaaa 600aagaaaagga gaaaggaagg accccgtgca agttccaaaa cttcttataa gaggaggagt 660agaagttcta gaagttaa 678391089DNAArtificial SequenceCodon-optimized BKV-IVc2 VP1 39atggcaccca caaagcgcaa gggcgaatgc cccggcgccg ccccaaagaa acccaaggag 60ccagtccagg tccccaagtt gctgatcaag ggcggcgtgg aggtcctgga ggtcaagacc 120ggcgtggacg ccatcaccga ggtggagtgt ttcttgaacc ccgagatggg cgaccccgac 180aacgatctgc gcgggtacag cttgcgcctg accgccgaga ccgcattcga ttccgactca 240cccgatcgca agatgttgcc atgctattcc accgcccgca tcccactgcc caacctcaac 300gaagacttga catgcggcaa cctgctgatg tgggaagccg tcaccgtgaa gaccgaagtc 360atcggcatca cctccatgtt gaatctgcac gccggaagcc aaaaggtgca cgagaacggc 420ggcgggaagc ccatccaggg gtcaaacttc catttcttcg ccgtcggcgg cgatccactc 480gagatgcaag gcgtgttgat gaactatcgc accaagtatc ccgagggcac cgtgacaccc 540aagaacccaa ccgcccaaag tcaggtcatg aacaccgatc acaaagcata tctcgataag 600aataacgcct accccgtcga gtgttggatc cccgatccat ccaagaacga gaacacccgc 660tacttcggca cctataccgg cggcgagaac gtcccacccg tgttgcacgt gacaaatacc 720gccacaaccg tcctgctcga cgagcaaggc gtcggcccac tctgcaaggc agacagcctc 780tacgtcagcg ccgccgacat ctgcggactg ttcaccaatt caagcggcac ccagcaatgg 840cgcgggttgc cccgctactt caaaatcagg ctccgcaagc gcagcgtgaa gaatccctat 900ccaatcagtt tcctgctgtc cgatttgatc aatcgccgca cacaacgcgt cgacggccag 960cccatgtacg gcatggaaag ccaagtcgaa gaagtgcgcg tcttcgacgg gaccgagcag 1020ttgcccggcg atcccgacat gatccgctac atcgatcgcc aaggccagct ccaaaccaag 1080atggtctga 1089401056DNAArtificial SequenceCodon-optimized BKV-IVc2 VP2 40atgggcgcag ctctggcatt gctcggagat ctggtcgcat ctgtgtccga agcagccgct 60gcaactggat tcagcgtcgc cgagatcgct gccggcgaag cagctgccgc aatcgaggtc 120cagatcgcaa gtctggccac tgtggaaggg atcacctcta caagcgaagc catcgctgcc 180atcggattga cccctcaaac ctacgccgtg atcgctggcg cacctggcgc aatcgctggt 240ttcgccgcac tgatccagac tgtcaccgga atctcgagcc tcgcccaggt cggatatcgg 300ttcttctcgg actgggacca taaggtcagt accgtggggt tgtaccaaca aagcgggatg 360gccctcgagc tcttcaatcc cgacgaatac tacgacatcc tgttccctgg cgtgaacacc 420ttcgtgaaca acatccagta tctggacccc cgccactggg gaccaagcct gttcgccaca 480atcagtcaag ccctctggca cgtcatccgc gacgacatcc ccgccatcac aagccaggag 540ctccagcgcc gcaccgaaag gtttttccgc gatagtctcg caagattcct cgaggagacc 600acatggacca tcgtgaacgc acccgtgaat ttctacaact acatccaaga ctactactcc 660aacctgagtc ccatccgccc aagcatggtc cgccaagtcg ccgagcgcga gggcacacaa 720gtgaacttcg ggcacacata tcgcatcgac gacgccgatt ccatccagga ggtcacacag 780cgcatggaac tgcgcaacaa ggaaaacgtg cacagcggcg aattcatcga gaagaccatc 840gcacccggcg gcgccaacca gcgcaccgcc ccacaatgga tgctcccact cttgctgggg 900ctctatggca ccgtgacccc tgccctggag gcctacgagg acgggccaaa tcagaaaaag 960cgccgcgtca gtcgcgggtc aagtcagaag gcaaagggca caagggcctc cgcaaagacc 1020accaacaagc gccgctcccg gtcgagccgc tcatga 105641699DNAArtificial SequenceCodon-optimized BKV-IVc2 VP3 41atggccctcg agctcttcaa tcccgacgaa tactacgaca tcctgttccc tggcgtgaac 60accttcgtga acaacatcca gtatctggac ccccgccact ggggaccaag cctgttcgcc 120acaatcagtc aagccctctg gcacgtcatc cgcgacgaca tccccgccat cacaagccag 180gagctccagc gccgcaccga aaggtttttc cgcgatagtc tcgcaagatt cctcgaggag 240accacatgga ccatcgtgaa cgcacccgtg aatttctaca actacatcca agactactac 300tccaacctga gtcccatccg cccaagcatg gtccgccaag tcgccgagcg cgagggcaca 360caagtgaact tcgggcacac atatcgcatc gacgacgccg attccatcca ggaggtcaca 420cagcgcatgg aactgcgcaa caaggaaaac gtgcacagcg gcgaattcat cgagaagacc 480atcgcacccg gcggcgccaa ccagcgcacc gccccacaat ggatgctccc actcttgctg 540gggctctatg gcaccgtgac ccctgccctg gaggcctacg aggacgggcc aaatcagaaa 600aagcgccgcg tcagtcgcgg gtcaagtcag aaggcaaagg gcacaagggc ctccgcaaag 660accaccaaca agcgccgctc ccggtcgagc cgctcatga 699421089DNAArtificial SequenceCodon-optimized BKV-Ia VP1 42atggcaccca caaagcgcaa gggcgaatgc cccggcgccg ccccaaagaa acccaaggag 60ccagtccagg tccccaagtt gctgatcaag ggcggcgtgg aggtcctgga ggtcaagacc 120ggcgtggacg ccatcaccga ggtggagtgt ttcttgaacc ccgagatggg cgaccccgac 180gagaacctgc gcgggttcag cttgaagctg agcgccgaga acgacttcag ctccgactca 240cccgaacgca agatgttgcc atgctattcc accgcccgca tcccactgcc caacctcaac 300gaagacttga catgcggcaa cctgctgatg tgggaagccg tcaccgtgca gaccgaagtc 360atcggcatca cctccatgtt gaatctgcac gccggaagcc aaaaggtgca cgagcacggc 420ggcgggaagc ccatccaggg gtcaaacttc catttcttcg ccgtcggcgg cgatccactc 480gagatgcaag gcgtgttgat gaactatcgc accaagtatc ccgacggcac catcacaccc 540aagaacccaa ccgcccaaag tcaggtcatg aacaccgatc acaaagcata tctcgataag 600aataacgcct accccgtcga gtgttgggtc cccgatccat cccggaacga gaacacccgc 660tacttcggca cctttaccgg cggcgagaac gtcccacccg tgttgcacgt gacaaatacc 720gccacaaccg tcctgctcga cgagcaaggc gtcggcccac tctgcaaggc agacagcctc 780tacgtcagcg ccgccgacat ctgcggactg ttcaccaatt caagcggcac ccagcaatgg 840cgcgggttgg cccgctactt caaaatcagg ctccgcaagc gcagcgtgaa gaatccctat 900ccaatcagtt tcctgctgtc cgatttgatc aatcgccgca cacaacgcgt cgacggccag 960cccatgtacg gcatggaaag ccaagtcgaa gaagtgcgcg tcttcgacgg gaccgagcgg 1020ttgcccggcg atcccgacat gatccgctac atcgataagc aaggccagct ccaaaccaag 1080atgctgtga 1089431089DNAArtificial SequenceCodon-optimizied BKV-Ib2 VP1 43atggcaccca caaagcgcaa gggcgaatgc cccggcgccg ccccaaagaa acccaaggag 60ccagtccagg tccccaagtt gctgatcaag ggcggcgtgg aggtcctgga ggtcaagacc 120ggcctggacg ccatcaccga ggtggagtgt ttcttgaacc ccgagatggg cgaccccgac 180gagaacctgc gcgggttcag cttgaagctg agcgccaaga acgacttcag ctccgactca 240cccgaccgca agatgttgcc atgctattcc accgcccgca tcccactgcc caacctcaac 300gaagacttga catgcggcaa cctgctgatg tgggaagccg tcaccgtgca gaccgaagtc 360atcggcatca cctccatgtt gaatctgcac gccggaagcc aaaaggtgca cgagcacggc 420ggcgggaagc ccatccaggg gtcaaacttc catttcttcg ccgtcggcgg cgatccactc 480gagatgcaag gcgtgttgat gaactatcgc accaagtatc ccgaaggcac catcacaccc 540aagaacccaa ccgcccaaag tcaggtcatg aacaccgatc acaaagcata tctcgataag 600aataacgcct accccgtcga gtgttggatc cccgatccat cccggaacga gaacacccgc 660tacttcggca cctttaccgg cggcgagaac gtcccacccg tgttgcacgt gacaaatacc 720gccacaaccg tcctgctcga cgagcaaggc gtcggcccac tctgcaaggc agacagcctc 780tacgtcagcg ccgccgacat ctgcggactg ttcaccaatt caagcggcac ccagcaatgg 840cgcgggttgg cccgctactt caaaatcagg ctccgcaagc gcagcgtgaa gaatccctat 900ccaatcagtt tcctgctgtc cgatttgatc aatcgccgca cacaacgcgt cgacggccag 960cccatgtacg gcatggaaag ccaagtcgaa gaagtgcgcg tcttcgacgg gaccgagcgg 1020ttgcccggcg atcccgacat gatccgctac atcgataagc aaggccagct ccaaaccaag 1080atgctgtga 1089441089DNAArtificial SequenceCodon-optimized BKV-Ic VP1 44atggcaccca caaagcgcaa gggcgaatgc cccggcgccg ccccaaagaa acccaaggag 60ccagtccagg tccccaagtt gctgatcaag ggcggcgtgg aggtcctgga ggtcaagacc 120ggcgtggacg ccatcaccga ggtggagtgt ttcttgaacc ccgagatggg cgaccccgac 180gagaacctgc gcgggttcag cttgaagctg agcgtcgaga acgacttcag ctccgactca 240ccccaacgca agatgttgcc atgctattcc accgcccgca tcccactgcc caacctcaac 300gaagacttga catgcggcaa cctgctgatg tgggaagccg tcaccgtgca gaccgaagtc 360atcggcatca cctccatgtt gaatctgcac gccggaagcc aaaaggtgca cgagcacggc 420ggcgggaagc ccatccaggg gtcaaacttc catttcttcg ccgtcggcgg cgatccactc 480gagatgcaag gcgtgttgat gaactatcgc accaagtatc ccgaaggcac catcacaccc 540aagaacccaa ccgcccaaag tcaggtcatg aacaccgatc acaaagcata tctcgataag 600aataacgcct accccgtcga gtgttggatc cccgatccat cccggaacga gaacacccgc 660tacttcggca ccttgaccgg cggcgagaac gtcccacccg tgttgcacgt gacaaatacc 720gccacaaccg tcctgctcga cgagcaaggc gtcggcccac tctgcaaggc agacagcctc 780tacgtcagcg ccgccgacat ctgcggactg ttcaccaatt caagcggcac ccagcaatgg 840cgcgggttgg cccgctactt caaaatcagg ctccgcaagc gcagcgtgaa gaatccctat 900ccaatcagtt tcctgctgtc cgatttgatc aatcgccgca cacaacgcgt cgacggccag 960cccatgtacg gcatggaaag ccaagtcgaa gaagtgcgcg tcttcgacgg gaccgagaag 1020ttgcccggcg atcccgacat gatccgctac atcgataagc aaggccagct ccaaaccaag 1080atgctgtga 1089451089DNAArtificial SequenceCodon-optimized BKV-II VP1 45atggcaccca caaagcgcaa gggcgaatgc cccggcgccg ccccaaagaa acccaaggag 60ccagtccagg tccccaagtt gctgatcaag ggcggcgtgg aggtcctgga ggtcaagacc 120ggcgtggacg ccatcaccga ggtggagtgt ttcttgaacc ccgagatggg cgaccccgac 180aacgatctgc gcgggtacag cttgaagctg accgccgaga acgcattcga ttccgactca 240cccgataaga agatgttgcc atgctattcc accgcccgca tcccactgcc caacctcaac 300gaagacttga catgcggcaa cctgctgatg tgggaagccg tcaccgtgaa gaccgaagtc 360atcggcatca cctccatgtt gaatctgcac gccggaagcc aaaaggtgca cgagaacggc 420ggcgggaagc ccgtccaggg gtcaaacttc catttcttcg ccgtcggcgg cgatccactc 480gagatgcaag gcgtgttgat gaactatcgc accaagtatc cccaaggcac catcacaccc 540aagaacccaa ccgcccaaag tcaggtcatg aacaccgatc acaaagcata tctcgataag 600aataacgcct accccgtcga gtgttggatc cccgatccat cccggaacga gaacacccgc 660tacttcggca cctataccgg cggcgagaac gtcccacccg tgttgcacgt gacaaatacc 720gccacaaccg tcctgctcga cgagcaaggc gtcggcccac tctgcaaggc agacagcctc 780tacgtcagcg ccgccgacat ctgcggactg ttcaccaatt caagcggcac ccagcaatgg 840cgcgggttgg cccgctactt caaaatcagg ctccgcaagc gcagcgtgaa gaatccctat 900ccaatcagtt tcctgctgtc cgatttgatc aatcgccgca cacaaaaggt cgacggccag 960cccatgtacg gcatggaaag ccaagtcgaa gaagtgcgcg tcttcgacgg gaccgagcag 1020ttgcccggcg atcccgacat gatccgctac atcgatcgcc aaggccagct ccaaaccaag 1080atggtctga 1089461089DNAArtificial SequenceCodon-optimized BKV-III VP1 46atggcaccca caaagcgcaa gggcgaatgc cccggcgccg ccccaaagaa acccaaggag 60ccagtccagg tccccaagtt gctgatcaag ggcggcgtgg aggtcctgga ggtcaagacc 120ggcgtggacg ccatcaccga ggtggagtgt ttcttgaacc ccgagatggg cgaccccgac 180gaccatctgc gcgggtacag ccagcacctg accgccgaga acgcattcga ttccgactca 240cccgataaga agatgttgcc atgctattcc accgcccgca tcccactgcc caacctcaac 300gaagacttga catgcggcaa cctgctgatg tgggaagccg tcaccgtgaa gaccgaagtc 360atcggcatca cctccatgtt gaatctgcac gccggaagcc aaaaggtgca cgagaacggc 420ggcgggaagc ccgtccaggg gtcaaacttc catttcttcg ccgtcggcgg cgatccactc 480gagatgcaag gcgtgttgat gaactatcgc accaagtatc cccaaggcac catcacaccc 540aagaacccaa ccgcccaaag tcaggtcatg aacaccgatc acaaagcata tctcgataag 600aataacgcct accccgtcga gtgttggatc cccgatccat ccaagaacga gaacacccgc 660tacttcggca cctataccgg cggcgagaac gtcccacccg tgttgcacgt gacaaatacc 720gccacaaccg tcctgctcga cgagcaaggc gtcggcccac tctgcaaggc agacagcctc 780tacgtcagcg ccgccgacat ctgcggactg ttcaccaatt caagcggcac ccagcaatgg 840cgcgggttgg cccgctactt caaaatcagg ctccgcaagc gcagcgtgaa gaatccctat 900ccaatcagtt tcctgctgtc cgatttgatc aatcgccgca cacaaaaggt cgacggccag 960cccatgtacg gcatggaaag ccaagtcgaa gaagtgcgcg tcttcgacgg gaccgagcag 1020ttgcccggcg atcccgacat gatccgctac atcgatcgcc aaggccagct ccaaaccaag 1080atggtctga 1089471089DNAArtificial SequenceCodon-optimized BKV-IVb1 VP1 47atggcaccca caaagcgcaa gggcgaatgc cccggcgccg ccccaaagaa acccaaggag 60ccagtccagg tccccaagtt gctgatcaag ggcggcgtgg aggtcctgga ggtcaagacc 120ggcgtggacg ccatcaccga ggtggagtgt ttcttgaacc ccgagatggg cgaccccgac 180aacgatctgc gcgggtacag cttgcgcctg accgccgaga ccgcattcaa ttccgactca 240cccgatcgca agatgttgcc atgctattcc accgcccgca tcccactgcc caacctcaac 300gaagacttga catgcggcaa cctgctgatg tgggaagccg tcaccgtgaa gaccgaagtc 360atcggcatca cctccatgtt gaatctgcac gccggaagcc aaaaggtgca cgacaacggc 420ggcgggaagc ccatccaggg gtcaaacttc catttcttcg ccgtcggcgg cgatccactc 480gagatgcaag gcgtgttgat gaactatcgc accaagtatc ccgagggcac cgtgacaccc 540aagaacccaa ccgcccaaag tcaggtcatg aacaccgatc acaaagcata tctcgataag 600aataacgcct accccgtcga gtgttggatc cccgatccat cccgaaacga gaacacccgc 660tacttcggca cctataccgg cggcgagaac gtcccacccg tgttgcacgt gacaaatacc 720gccacaaccg tcctgctcga cgagcaaggc gtcggcccac tctgcaaggc agacagcctc 780tacgtcagcg ccgccgacat ctgcggactg ttcaccaatt caagcggcac ccagcaatgg 840cgcgggttgc cccgctactt caaaatcagg ctccgcaagc gcagcgtgaa gaatccctat 900ccaatcagtt tcctgctgtc cgatttgatc aatcgccgca cacaacgcgt cgacggccag 960cccatgtacg gcatggaaag ccaagtcgaa gaagtgcgcg tcttcgacgg gaccgagaag 1020ttgcccggcg atcccgacat gatccgctac atcgatcgcc aaggccagct ccaaaccaag 1080atggtctga 1089481065DNAArtificial SequenceCodon-optimized JCV-2A VP1 48atggcaccca caaagcgcaa gggcgaacgc aaggacccag tccaggtccc caagttgctg 60atcaggggcg gcgtggaggt cctggaggtc aagaccggcg tggactccat caccgaggtg 120gagtgtttct tgacacccga gatgggcgac cccgacgagc acctgcgcgg gttcagcaag 180agcatcagca tcagcgacac attcgagtcc gactcaccca ataaggacat gttgccatgc 240tattccgtcg cccgcatccc actgcccaac ctcaacgaag acttgacatg cggcaacatc 300ctgatgtggg aagccgtcac actgaagacc gaagtcatcg gcgtcaccac cctgatgaat 360gtgcactcca acggccaagc gacgcacgac aacggcgccg ggaagccagt ccaggggaca 420agcttccatt tcttcagcgt cggcggcgag gcactcgagc tgcaaggcgt ggtgttcaac 480tatcgcacca agtatcccga cggcaccata ttccccaaga acgcaaccgt ccaaagtcag 540gtcatgaaca ccgagcacaa agcatatctc gataagaata aggcctaccc cgtcgagtgt 600tgggtccccg atccaaccag gaacgagaac acccgctact tcggcaccct gaccggcggc 660gagaacgtcc cacccgtgtt gcacatcaca aataccgcca caaccgtcct gctcgacgag 720ttcggcgtcg gcccactctg caagggagac aacctctacc tgagcgccgt cgacgtctgc 780ggaatgttca ccaatcgaag cggcagccag caatggcgcg ggttgtcccg ctacttcaaa 840gtccagctcc gcaagcgccg cgtgaagaat ccctatccaa tcagtttcct gctgaccgat 900ttgatcaatc gccgcacacc acgcgtcgac ggccagccca tgtacggcat ggacgcccaa 960gtcgaagaag tgcgcgtatt cgaggggacc gaggagttgc ccggcgatcc cgacatgatg 1020cgctacgtcg atcgctacgg ccagctccaa accaagatgc tatga 1065491065DNAArtificial SequenceCodon-optimzed JCV-3B VP1 49atggcaccca

caaagcgcaa gggcgaacgc aaggacccag tccaggtccc caagttgctg 60atcaggggcg gcgtggaggt cctggaggtc aagaccggcg tggactccat caccgaggtg 120gagtgtttct tgacacccga gatgggcgac cccgacgagc acttccgcgg gttcagcaag 180agcatcagca tcagcgacac attcgagtcc gactcaccca ataaggacat gttgccatgc 240tattccgtcg cccgcatccc actgcccaac ctcaacgaag acttgacatg cggcaacatc 300ctgatgtggg aagccgtcac actgaagacc gaagtcatcg gcgtcaccac cctgatgaat 360gtgcactcca acggccaagc gacgcacgac aacggcgccg cgaagccagt ccaggggaca 420agcttccatt tcttcagcgt cggcggcgag gcactcgagc tgcaaggcgt ggtgttcaac 480tatcgcacca cgtatcccga cggcaccata ttccccaaga acgcaaccgt ccaaagtcag 540gtcatgaaca ccgagcacaa agcatatctc gataagaata aggcctaccc cgtcgagtgt 600tgggtccccg atccaaccag gaacgagaac acccgctact tcggcaccct gaccggcggc 660gagaacgtcc cacccgtgtt gcacatcaca aataccgcca caaccgtcct gctcgacgag 720ttcggcgtcg gcccactctg caagggagac aacctctacc tgagcgccgt cgacgtctgc 780ggaatgttca ccaatcgaag cggcagccag caatggcgcg ggttgtcccg ctacttcaaa 840gtccagctcc gcaagcgccg cgtgaagaat ccctatccaa tcagtttcct gctgaccgat 900ttgatcaatc gccgcacacc acgcgtcgac ggccagccca tgtacggcat ggacgcccaa 960atcgaagaag tgcgcgtatt cgaggggacc gagcagttgc ccggcgatcc cgacatgatg 1020cgctacgtcg atcgctacgg ccagctccaa accaagatgc tatga 1065501035DNAArtificial SequenceCodon-optimized JCV VP2 consensus 50atgggcgcag ctctggcctt gctcggcgat ctggtcgcca ccgtcagcga agccgcagcc 60gcaaccggat tcagcgtggc cgagatcgca gccggagaag ctgcagccac aatcgaggtc 120gagatcgcca gtttggccac tgtggaaggc atcacctcca caagcgaagc catcgctgcc 180atcggactga cacccgagac ctacgccgtg atcactggcg cacccggagc cgtggcagga 240ttcgccgcac tcgtccaaac cgtgaccggc ggctccgcca tcgcccaact cgggtaccgg 300ttcttcgccg attgggacca caaggtcagc accgtcggct tgttccaaca acccgcaatg 360gcactgcagc tgttcaaccc cgaggactac tacgacatcc tgttcccggg cgtcaacgca 420ttcgtcaaca acatccatta cctggaccca cgccactggg ggcccagcct gttttcgacc 480attagtcaag cattctggaa cttggtccgc gacgacctgc caagcctgac cagccaagag 540atccagcgcc gcacacagaa gttgttcgtc gagtccctgg cccgcttcct ggaagagaca 600acctgggcca tcgtcaacag ccccgtcaat ctgtacaact acatcagcga ttactactcg 660cgactcagcc ccgtccgccc aagcatggtc cgccaagtcg cacagcgcga aggcacatac 720atcagtttcg ggcatagcta tacacagtcc atcgacgacg ccgattcaat ccaggaggtc 780acacagcgct tggacctgaa gacacccaac gtccagagcg gcgagttcat cgaaaagtcc 840atcgcccctg gcggagcaaa ccagcgcagc gcaccacaat ggatgctgcc actgttgctg 900ggcctctatg gcaccgtgac cccagcactg gaggcctacg aggacggacc aaacaagaaa 960aagcgccgca aggaaggccc aagggcatcc agcaagacca gctacaaacg tcggtccagg 1020tccagccgct cctga 103551678DNAArtificial SequenceCodon-optimized JCV VP3 consensus 51atggcactgc agctgttcaa ccccgaggac tactacgaca tcctgttccc gggcgtcaac 60gcattcgtca acaacatcca ttacctggac ccacgccact gggggcccag cctgttttcg 120accattagtc aagcattctg gaacttggtc cgcgacgacc tgccaagcct gaccagccaa 180gagatccagc gccgcacaca gaagttgttc gtcgagtccc tggcccgctt cctggaagag 240acaacctggg ccatcgtcaa cagccccgtc aatctgtaca actacatcag cgattactac 300tcgcgactca gccccgtccg cccaagcatg gtccgccaag tcgcacagcg cgaaggcaca 360tacatcagtt tcgggcatag ctatacacag tccatcgacg acgccgattc aatccaggag 420gtcacacagc gcttggacct gaagacaccc aacgtccaga gcggcgagtt catcgaaaag 480tccatcgccc ctggcggagc aaaccagcgc agcgcaccac aatggatgct gccactgttg 540ctgggcctct atggcaccgt gaccccagca ctggaggcct acgaggacgg accaaacaag 600aaaaagcgcc gcaaggaagg cccaagggca tccagcaaga ccagctacaa acgtcggtcc 660aggtccagcc gctcctga 67852362PRTBK virus 52Met Ala Pro Thr Lys Arg Lys Gly Glu Cys Pro Gly Ala Ala Pro Lys 1 5 10 15 Lys Pro Lys Glu Pro Val Gln Val Pro Lys Leu Leu Ile Lys Gly Gly 20 25 30 Val Glu Val Leu Glu Val Lys Thr Gly Val Asp Ala Ile Thr Glu Val 35 40 45 Glu Cys Phe Leu Asn Pro Glu Met Gly Asp Pro Asp Glu Asn Leu Arg 50 55 60 Gly Phe Ser Leu Lys Leu Ser Ala Glu Asn Asp Phe Ser Ser Asp Ser 65 70 75 80 Pro Glu Arg Lys Met Leu Pro Cys Tyr Ser Thr Ala Arg Ile Pro Leu 85 90 95 Pro Asn Leu Asn Glu Asp Leu Thr Cys Gly Asn Leu Leu Met Trp Glu 100 105 110 Ala Val Thr Val Gln Thr Glu Val Ile Gly Ile Thr Ser Met Leu Asn 115 120 125 Leu His Ala Gly Ser Gln Lys Val His Glu His Gly Gly Gly Lys Pro 130 135 140 Ile Gln Gly Ser Asn Phe His Phe Phe Ala Val Gly Gly Asp Pro Leu 145 150 155 160 Glu Met Gln Gly Val Leu Met Asn Tyr Arg Thr Lys Tyr Pro Asp Gly 165 170 175 Thr Ile Thr Pro Lys Asn Pro Thr Ala Gln Ser Gln Val Met Asn Thr 180 185 190 Asp His Lys Ala Tyr Leu Asp Lys Asn Asn Ala Tyr Pro Val Glu Cys 195 200 205 Trp Val Pro Asp Pro Ser Arg Asn Glu Asn Thr Arg Tyr Phe Gly Thr 210 215 220 Phe Thr Gly Gly Glu Asn Val Pro Pro Val Leu His Val Thr Asn Thr 225 230 235 240 Ala Thr Thr Val Leu Leu Asp Glu Gln Gly Val Gly Pro Leu Cys Lys 245 250 255 Ala Asp Ser Leu Tyr Val Ser Ala Ala Asp Ile Cys Gly Leu Phe Thr 260 265 270 Asn Ser Ser Gly Thr Gln Gln Trp Arg Gly Leu Ala Arg Tyr Phe Lys 275 280 285 Ile Arg Leu Arg Lys Arg Ser Val Lys Asn Pro Tyr Pro Ile Ser Phe 290 295 300 Leu Leu Ser Asp Leu Ile Asn Arg Arg Thr Gln Arg Val Asp Gly Gln 305 310 315 320 Pro Met Tyr Gly Met Glu Ser Gln Val Glu Glu Val Arg Val Phe Asp 325 330 335 Gly Thr Glu Arg Leu Pro Gly Asp Pro Asp Met Ile Arg Tyr Ile Asp 340 345 350 Lys Gln Gly Gln Leu Gln Thr Lys Met Leu 355 360 53362PRTBK virus 53Met Ala Pro Thr Lys Arg Lys Gly Glu Cys Pro Gly Ala Ala Pro Lys 1 5 10 15 Lys Pro Lys Glu Pro Val Gln Val Pro Lys Leu Leu Ile Lys Gly Gly 20 25 30 Val Glu Val Leu Glu Val Lys Thr Gly Val Asp Ala Ile Thr Glu Val 35 40 45 Glu Cys Phe Leu Asn Pro Glu Met Gly Asp Pro Asp Glu Asn Leu Arg 50 55 60 Gly Phe Ser Leu Lys Leu Ser Ala Glu Asn Asp Phe Ser Ser Asp Ser 65 70 75 80 Pro Glu Arg Lys Met Leu Pro Cys Tyr Ser Thr Ala Arg Ile Pro Leu 85 90 95 Pro Asn Leu Asn Glu Asp Leu Thr Cys Gly Asn Leu Leu Met Trp Glu 100 105 110 Ala Val Thr Val Gln Thr Glu Val Ile Gly Ile Thr Ser Met Leu Asn 115 120 125 Leu His Ala Gly Ser Gln Lys Val His Glu His Gly Gly Gly Lys Pro 130 135 140 Ile Gln Gly Ser Asn Phe His Phe Phe Ala Val Gly Gly Asp Pro Leu 145 150 155 160 Glu Met Gln Gly Val Leu Met Asn Tyr Arg Thr Lys Tyr Pro Asp Gly 165 170 175 Thr Ile Thr Pro Lys Asn Pro Thr Ala Gln Ser Gln Val Met Asn Thr 180 185 190 Asp His Lys Ala Tyr Leu Asp Lys Asn Asn Ala Tyr Pro Val Glu Cys 195 200 205 Trp Val Pro Asp Pro Ser Arg Asn Glu Asn Thr Arg Tyr Phe Gly Thr 210 215 220 Phe Thr Gly Gly Glu Asn Val Pro Pro Val Leu His Val Thr Asn Thr 225 230 235 240 Ala Thr Thr Val Leu Leu Asp Glu Gln Gly Val Gly Pro Leu Cys Lys 245 250 255 Ala Asp Ser Leu Tyr Val Ser Ala Ala Asp Ile Cys Gly Leu Phe Thr 260 265 270 Asn Ser Ser Gly Thr Gln Gln Trp Arg Gly Leu Ala Arg Tyr Phe Lys 275 280 285 Ile Arg Leu Arg Lys Arg Ser Val Lys Asn Pro Tyr Pro Ile Ser Phe 290 295 300 Leu Leu Ser Asp Leu Ile Asn Arg Arg Thr Gln Arg Val Asp Gly Gln 305 310 315 320 Pro Met Tyr Gly Met Glu Ser Gln Val Glu Glu Val Arg Val Phe Asp 325 330 335 Gly Thr Glu Arg Leu Pro Gly Asp Pro Asp Met Ile Arg Tyr Ile Asp 340 345 350 Lys Gln Gly Gln Leu Gln Thr Lys Met Leu 355 360 54362PRTBK virus 54Met Ala Pro Thr Lys Arg Lys Gly Glu Cys Pro Gly Ala Ala Pro Lys 1 5 10 15 Lys Pro Lys Glu Pro Val Gln Val Pro Lys Leu Leu Ile Lys Gly Gly 20 25 30 Val Glu Val Leu Glu Val Lys Thr Gly Val Asp Ala Ile Thr Glu Val 35 40 45 Glu Cys Phe Leu Asn Pro Glu Ile Gly Asp Pro Asp Glu Asn Leu Arg 50 55 60 Gly Phe Ser Leu Lys Leu Ser Ala Glu Asn Asp Phe Ser Ser Asp Ser 65 70 75 80 Pro Glu Arg Lys Met Leu Pro Cys Tyr Ser Thr Ala Arg Ile Pro Leu 85 90 95 Pro Asn Leu Asn Glu Asp Leu Thr Cys Gly Asn Leu Leu Met Trp Glu 100 105 110 Ala Val Thr Val Gln Thr Glu Val Ile Gly Ile Thr Ser Met Leu Asn 115 120 125 Leu His Ala Gly Ser Gln Lys Val His Glu His Gly Gly Gly Lys Pro 130 135 140 Ile Gln Gly Ser Asn Phe His Phe Phe Ala Val Gly Gly Asp Pro Leu 145 150 155 160 Glu Met Gln Gly Val Leu Met Asn Tyr Arg Thr Lys Tyr Pro Asp Gly 165 170 175 Thr Ile Thr Pro Lys Asn Pro Thr Ala Gln Ser Gln Val Met Asn Thr 180 185 190 Asp His Lys Ala Tyr Leu Asp Lys Asn Asn Ala Tyr Pro Val Glu Cys 195 200 205 Trp Val Pro Asp Pro Ser Arg Asn Glu Asn Thr Arg Tyr Phe Gly Thr 210 215 220 Phe Thr Gly Gly Glu Asn Val Pro Pro Val Leu His Val Thr Asn Thr 225 230 235 240 Ala Thr Thr Val Leu Leu Asp Glu Gln Gly Val Gly Pro Leu Cys Lys 245 250 255 Ala Asp Ser Leu Tyr Val Ser Ala Ala Asp Ile Cys Gly Leu Phe Thr 260 265 270 Asn Ser Ser Gly Thr Gln Gln Trp Arg Gly Leu Ala Arg Tyr Phe Lys 275 280 285 Ile Arg Leu Arg Lys Arg Ser Val Lys Asn Pro Tyr Pro Ile Ser Phe 290 295 300 Leu Leu Ser Asp Leu Ile Asn Arg Arg Thr Gln Arg Val Asp Gly Gln 305 310 315 320 Pro Met Tyr Gly Met Glu Ser Gln Val Glu Glu Val Arg Val Phe Asp 325 330 335 Gly Thr Glu Arg Leu Pro Gly Asp Pro Asp Met Ile Arg Tyr Ile Asp 340 345 350 Lys Gln Gly Gln Leu Gln Thr Lys Met Leu 355 360 55362PRTBK virus 55Met Ala Pro Thr Lys Arg Lys Gly Glu Cys Pro Gly Ala Ala Pro Lys 1 5 10 15 Lys Pro Lys Glu Pro Val Gln Val Pro Lys Leu Leu Ile Lys Gly Gly 20 25 30 Val Glu Val Leu Glu Val Lys Thr Gly Val Asp Ala Ile Thr Glu Val 35 40 45 Glu Cys Phe Leu Asn Pro Glu Met Gly Asp Pro Asp Glu Asn Leu Arg 50 55 60 Gly Phe Ser Leu Lys Leu Ser Ala Glu Asn Asp Phe Ser Ser Asp Ser 65 70 75 80 Pro Glu Arg Lys Met Leu Pro Cys Tyr Ser Thr Ala Arg Ile Pro Leu 85 90 95 Pro Asn Leu Asn Glu Asp Leu Thr Cys Gly Asn Leu Leu Met Trp Glu 100 105 110 Ala Val Thr Val Gln Thr Glu Val Ile Gly Ile Thr Ser Met Pro Asn 115 120 125 Leu His Ala Gly Ser Gln Lys Val His Glu His Gly Gly Gly Lys Pro 130 135 140 Ile Gln Gly Ser Asn Phe His Phe Phe Ala Val Gly Gly Asp Pro Leu 145 150 155 160 Glu Met Gln Gly Val Leu Met Asn Tyr Arg Thr Lys Tyr Pro Asp Gly 165 170 175 Thr Ile Thr Pro Lys Asn Pro Thr Ala Gln Ser Gln Val Met Asn Thr 180 185 190 Asp His Lys Ala Tyr Leu Asp Lys Asn Asn Ala Tyr Pro Val Glu Cys 195 200 205 Trp Val Pro Asp Pro Ser Arg Asn Glu Asn Thr Arg Tyr Phe Gly Thr 210 215 220 Phe Thr Gly Gly Glu Asn Val Pro Pro Val Leu His Val Thr Asn Thr 225 230 235 240 Ala Thr Thr Val Leu Leu Asp Glu Gln Gly Val Gly Pro Leu Cys Lys 245 250 255 Ala Asp Ser Leu Tyr Val Ser Ala Ala Asp Ile Cys Gly Leu Phe Thr 260 265 270 Asn Ser Ser Gly Thr Gln Gln Trp Arg Gly Leu Ala Arg Tyr Phe Lys 275 280 285 Ile Arg Leu Arg Lys Arg Ser Val Lys Asn Pro Tyr Pro Ile Ser Phe 290 295 300 Leu Leu Ser Asp Leu Ile Asn Arg Arg Thr Gln Arg Val Asp Gly Gln 305 310 315 320 Pro Met Tyr Gly Met Glu Ser Gln Val Glu Glu Val Arg Val Phe Asp 325 330 335 Gly Thr Glu Arg Leu Pro Gly Asp Pro Asp Met Ile Arg Tyr Ile Asp 340 345 350 Lys Gln Gly Gln Leu Gln Thr Lys Met Leu 355 360 56362PRTBK virus 56Met Ala Pro Thr Lys Arg Lys Gly Glu Cys Pro Gly Ala Ala Pro Lys 1 5 10 15 Lys Pro Glu Glu Pro Val Gln Val Pro Lys Leu Leu Ile Lys Gly Gly 20 25 30 Val Glu Val Leu Glu Val Lys Thr Gly Val Asp Ala Ile Thr Glu Val 35 40 45 Glu Cys Phe Leu Asn Pro Glu Met Gly Asp Pro Asp Glu Asn Leu Arg 50 55 60 Gly Phe Ser Leu Lys Leu Ser Ala Glu Asn Asp Phe Ser Ser Asp Ser 65 70 75 80 Pro Glu Arg Lys Met Leu Pro Cys Tyr Ser Thr Ala Arg Ile Pro Leu 85 90 95 Pro Asn Leu Asn Glu Asp Leu Thr Cys Gly Asn Leu Leu Met Trp Glu 100 105 110 Ala Val Thr Val Gln Thr Glu Val Ile Gly Ile Thr Ser Met Leu Asn 115 120 125 Leu His Ala Gly Ser Gln Lys Val His Glu His Gly Gly Gly Lys Pro 130 135 140 Ile Gln Gly Ser Asn Phe His Phe Phe Ala Val Gly Gly Asp Pro Leu 145 150 155 160 Glu Met Gln Gly Val Leu Met Asn Tyr Arg Thr Lys Tyr Pro Asp Gly 165 170 175 Thr Ile Thr Pro Lys Asn Pro Thr Ala Gln Ser Gln Val Met Asn Thr 180 185 190 Asp His Lys Ala Tyr Leu Asp Lys Asn Asn Ala Tyr Pro Val Glu Cys 195 200 205 Trp Val Pro Asp Pro Ser Arg Asn Glu Asn Thr Arg Tyr Phe Gly Thr 210 215 220 Phe Thr Gly Gly Glu Asn Val Pro Pro Val Leu His Val Thr Asn Thr 225 230 235 240 Ala Thr Thr Val Leu Leu Asp Glu Gln Gly Val Gly Pro Leu Cys Lys 245 250 255 Ala Asp Ser Leu Tyr Val Ser Ala Ala Asp Ile Cys Gly Leu Phe Thr 260 265 270 Asn Ser Ser Gly Thr Gln Gln Trp Arg Gly Leu Ala Arg Tyr Phe Lys 275 280 285 Ile Arg Leu Arg Lys Arg Ser Val Lys Asn Pro Tyr Pro Ile Ser Phe 290 295 300 Leu Leu Ser Asp Leu Ile Asn Arg Arg Thr Gln Arg Val Asp Gly Gln 305 310 315 320 Pro Met Tyr Gly Met Glu Ser Gln Val Glu Glu Val Arg Val Phe Asp 325 330 335 Gly Thr Glu Arg Leu Pro Gly Asp Pro Asp Met Ile Arg Tyr Ile Asp 340 345 350 Lys Gln Gly Gln Leu Gln Thr Lys Met Leu 355 360 57362PRTBK virus 57Met Ala Pro Thr Lys Arg Lys Gly Glu Cys Pro Gly Ala Ala Pro Lys 1 5 10 15 Lys Pro Lys Glu Pro Val Gln Val Pro Lys Leu

Leu Ile Lys Gly Gly 20 25 30 Val Glu Val Leu Glu Val Lys Thr Gly Val Asp Ala Ile Thr Glu Val 35 40 45 Glu Cys Phe Leu Asn Pro Glu Met Gly Asp Pro Asp Glu Asn Leu Arg 50 55 60 Gly Phe Ser Leu Lys Leu Ser Ala Glu Asn Asp Phe Ser Ser Asp Ser 65 70 75 80 Pro Glu Arg Lys Met Leu Pro Cys Tyr Ser Thr Ala Arg Ile Pro Leu 85 90 95 Pro Asn Leu Asn Glu Asp Leu Thr Cys Gly Asn Leu Leu Met Trp Glu 100 105 110 Ala Val Thr Val Gln Thr Glu Val Ile Gly Ile Thr Ser Met Leu Asn 115 120 125 Leu His Ala Gly Ser Gln Lys Val His Glu His Gly Gly Gly Lys Pro 130 135 140 Ile Gln Gly Ser Asn Phe His Phe Phe Ala Val Gly Gly Asp Pro Leu 145 150 155 160 Glu Met Gln Gly Val Leu Leu Asn Tyr Arg Thr Lys Tyr Pro Asp Gly 165 170 175 Thr Ile Thr Pro Lys Asn Pro Thr Ala Gln Ser Gln Val Met Asn Thr 180 185 190 Asp His Lys Ala Tyr Leu Asp Lys Asn Asn Ala Tyr Pro Val Glu Cys 195 200 205 Trp Val Pro Asp Pro Ser Arg Asn Glu Asn Thr Arg Tyr Phe Gly Thr 210 215 220 Phe Thr Gly Gly Glu Asn Val Pro Pro Val Leu His Val Thr Asn Thr 225 230 235 240 Ala Thr Thr Val Leu Leu Asp Glu Gln Gly Val Gly Pro Leu Cys Lys 245 250 255 Ala Asp Ser Leu Tyr Val Ser Ala Ala Asp Ile Cys Gly Leu Phe Thr 260 265 270 Asn Ser Ser Gly Thr Gln Gln Trp Arg Gly Leu Ala Arg Tyr Phe Lys 275 280 285 Ile Arg Leu Arg Lys Arg Ser Val Lys Asn Pro Tyr Pro Ile Ser Phe 290 295 300 Leu Leu Ser Asp Leu Ile Asn Arg Arg Thr Gln Arg Val Asp Gly Gln 305 310 315 320 Pro Met Tyr Gly Met Glu Ser Gln Val Glu Glu Val Arg Val Phe Asp 325 330 335 Gly Thr Glu Arg Leu Pro Gly Asp Pro Asp Met Ile Arg Tyr Ile Asp 340 345 350 Lys Gln Gly Gln Leu Gln Thr Lys Met Leu 355 360 58362PRTBK virus 58Met Ala Pro Thr Lys Arg Lys Gly Glu Cys Pro Gly Ala Ala Pro Lys 1 5 10 15 Lys Pro Lys Glu Pro Val Gln Val Pro Lys Leu Leu Ile Lys Gly Gly 20 25 30 Val Glu Val Leu Glu Val Lys Thr Gly Val Asp Ala Ile Thr Glu Val 35 40 45 Glu Cys Phe Leu Asn Pro Glu Met Gly Asp Pro Asp Glu Asn Leu Arg 50 55 60 Gly Phe Ser Leu Lys Leu Ser Ala Glu Asn Asp Phe Ser Ser Asp Ser 65 70 75 80 Pro Glu Arg Lys Met Leu Pro Cys Tyr Ser Thr Ala Arg Ile Pro Leu 85 90 95 Pro Asn Leu Asn Glu Asp Leu Thr Cys Gly Asn Leu Leu Met Trp Glu 100 105 110 Ala Val Thr Val Gln Thr Glu Val Ile Gly Ile Thr Ser Met Leu Asn 115 120 125 Leu His Ala Gly Ser Gln Lys Val His Glu His Gly Gly Gly Lys Pro 130 135 140 Ile Gln Gly Ser Asn Phe His Phe Phe Ala Val Gly Gly Asp Pro Leu 145 150 155 160 Glu Met Gln Gly Val Leu Met Asn Tyr Arg Thr Lys Tyr Pro Asp Gly 165 170 175 Thr Val Thr Pro Lys Asn Pro Thr Ala Gln Ser Gln Val Met Asn Thr 180 185 190 Asp His Lys Ala Tyr Leu Asp Lys Asn Asn Ala Tyr Pro Val Glu Cys 195 200 205 Trp Val Pro Asp Pro Ser Arg Asn Glu Asn Thr Arg Tyr Phe Gly Thr 210 215 220 Phe Thr Gly Gly Glu Asn Val Pro Pro Val Leu His Val Thr Asn Thr 225 230 235 240 Ala Thr Thr Val Leu Leu Asp Glu Gln Gly Val Gly Pro Leu Cys Lys 245 250 255 Ala Asp Ser Leu Tyr Val Ser Ala Ala Asp Ile Cys Gly Leu Phe Thr 260 265 270 Asn Ser Ser Gly Thr Gln Gln Trp Arg Gly Leu Ala Arg Tyr Phe Lys 275 280 285 Ile Arg Leu Arg Lys Arg Ser Val Lys Asn Pro Tyr Pro Ile Ser Phe 290 295 300 Leu Leu Ser Asp Leu Ile Asn Arg Arg Thr Gln Arg Val Asp Gly Gln 305 310 315 320 Pro Met Tyr Gly Met Glu Ser Gln Val Glu Glu Val Arg Val Phe Asp 325 330 335 Gly Thr Glu Arg Leu Pro Gly Asp Pro Asp Met Ile Arg Tyr Ile Asp 340 345 350 Lys Gln Gly Gln Leu Gln Thr Lys Met Leu 355 360 59362PRTBK virus 59Met Ala Pro Thr Lys Arg Lys Gly Glu Cys Pro Gly Ala Ala Pro Lys 1 5 10 15 Lys Pro Lys Glu Pro Val Gln Val Pro Lys Leu Leu Ile Lys Gly Gly 20 25 30 Val Glu Val Leu Glu Val Lys Thr Gly Val Asp Ala Ile Thr Glu Val 35 40 45 Glu Cys Phe Leu Asn Pro Glu Met Gly Asp Ser Asp Glu Asn Leu Arg 50 55 60 Gly Phe Ser Leu Lys Leu Ser Ala Glu Asn Asp Phe Ser Ser Asp Ser 65 70 75 80 Pro Glu Arg Lys Met Leu Pro Cys Tyr Ser Thr Ala Arg Ile Pro Leu 85 90 95 Pro Asn Leu Asn Glu Asp Leu Thr Cys Gly Asn Leu Leu Met Trp Glu 100 105 110 Ala Val Thr Val Gln Thr Glu Val Ile Gly Ile Thr Ser Met Leu Asn 115 120 125 Leu His Ala Gly Ser Gln Lys Val His Glu His Gly Gly Gly Lys Pro 130 135 140 Ile Gln Gly Ser Asn Phe His Phe Phe Ala Val Gly Gly Asp Pro Leu 145 150 155 160 Glu Met Gln Gly Val Leu Met Asn Tyr Arg Thr Lys Tyr Pro Asp Gly 165 170 175 Thr Val Thr Pro Lys Asn Pro Thr Ala Gln Ser Gln Val Met Asn Thr 180 185 190 Asp His Lys Ala Tyr Leu Asp Lys Asn Asn Ala Tyr Pro Val Glu Cys 195 200 205 Trp Val Pro Asp Pro Ser Arg Asn Glu Asn Thr Arg Tyr Phe Gly Thr 210 215 220 Phe Thr Gly Gly Glu Asn Val Pro Pro Val Leu His Val Thr Asn Thr 225 230 235 240 Ala Thr Thr Val Leu Leu Asp Glu Gln Gly Val Gly Pro Leu Cys Lys 245 250 255 Ala Asp Ser Leu Tyr Val Ser Ala Ala Asp Ile Cys Gly Leu Phe Thr 260 265 270 Asn Ser Ser Gly Thr Gln Gln Trp Arg Gly Leu Ala Arg Tyr Phe Lys 275 280 285 Ile Arg Leu Arg Lys Arg Ser Val Lys Asn Pro Tyr Pro Ile Ser Phe 290 295 300 Leu Leu Ser Asp Leu Ile Asn Arg Arg Thr Gln Arg Val Asp Gly Gln 305 310 315 320 Pro Met Tyr Gly Met Glu Ser Gln Val Glu Glu Val Arg Val Phe Asp 325 330 335 Gly Thr Glu Arg Leu Pro Gly Asp Pro Asp Met Ile Arg Tyr Ile Asp 340 345 350 Lys Gln Gly Gln Leu Gln Thr Lys Met Leu 355 360 60362PRTBK virus 60Met Ala Pro Thr Lys Arg Lys Gly Glu Cys Pro Gly Ala Ala Pro Lys 1 5 10 15 Lys Pro Lys Glu Pro Val Gln Val Pro Lys Leu Leu Ile Lys Gly Gly 20 25 30 Val Glu Val Leu Glu Val Lys Thr Gly Val Asp Ala Ile Thr Glu Val 35 40 45 Glu Cys Phe Leu Asn Pro Glu Met Gly Asp Pro Asp Glu Asn Leu Arg 50 55 60 Gly Phe Ser Leu Lys Leu Ser Ala Glu Asn Asp Phe Ser Ser Asp Ser 65 70 75 80 Pro Glu Arg Lys Met Leu Pro Cys Tyr Ser Thr Ala Arg Ile Pro Leu 85 90 95 Pro Asn Leu Asn Glu Asp Leu Thr Cys Gly Asn Leu Leu Met Trp Glu 100 105 110 Ala Val Thr Val Gln Thr Glu Val Ile Gly Ile Thr Ser Met Leu Asn 115 120 125 Leu His Ala Gly Ser Gln Lys Val His Glu His Gly Gly Gly Lys Pro 130 135 140 Ile Gln Gly Ser Asn Phe His Phe Phe Ala Val Gly Gly Asp Pro Leu 145 150 155 160 Glu Met Gln Gly Val Leu Met Asn Tyr Arg Thr Lys Tyr Pro Asp Gly 165 170 175 Thr Ile Thr Pro Lys Asn Pro Thr Ala Gln Ser Gln Val Met Asn Thr 180 185 190 Asp His Lys Ala Tyr Leu Asp Lys Asn Asn Ala Tyr Pro Val Glu Cys 195 200 205 Trp Val Pro Asp Pro Ser Arg Asn Glu Asn Thr Arg Tyr Phe Gly Thr 210 215 220 Phe Thr Gly Gly Glu Asn Val Pro Pro Val Leu His Val Thr Asn Thr 225 230 235 240 Ala Thr Thr Val Leu Leu Asp Glu Gln Gly Val Gly Pro Leu Cys Lys 245 250 255 Ala Asp Ser Leu Tyr Val Ser Ala Ala Asp Ile Cys Gly Leu Phe Thr 260 265 270 Asn Ser Ser Gly Thr Gln Gln Trp Arg Gly Leu Ala Arg Tyr Phe Lys 275 280 285 Ile Arg Leu Arg Lys Arg Ser Val Lys Asn Pro Tyr Pro Ile Ser Phe 290 295 300 Leu Leu Ser Asp Leu Ile Asn Arg Arg Thr Gln Arg Val Asp Gly Gln 305 310 315 320 Pro Met Tyr Gly Met Glu Ser Gln Val Glu Glu Val Arg Val Phe Asp 325 330 335 Gly Thr Glu Arg Leu Pro Gly Asp Pro Asp Met Ile Arg Tyr Ile Asp 340 345 350 Arg Gln Gly Gln Leu Gln Thr Lys Met Leu 355 360 61362PRTBK virus 61Met Ala Pro Thr Lys Arg Lys Gly Glu Cys Pro Gly Ala Ala Pro Lys 1 5 10 15 Lys Pro Lys Glu Pro Val Gln Val Pro Lys Leu Leu Ile Lys Gly Gly 20 25 30 Val Glu Val Leu Glu Val Lys Thr Gly Val Asp Ala Ile Thr Glu Val 35 40 45 Glu Cys Phe Leu Asn Pro Glu Met Gly Asp Pro Asp Glu Asn Leu Arg 50 55 60 Gly Phe Ser Leu Lys Leu Ser Ala Glu Asn Asp Phe Ser Ser Asp Ser 65 70 75 80 Pro Glu Arg Lys Met Leu Pro Cys Tyr Ser Thr Ala Arg Ile Pro Leu 85 90 95 Pro Asn Leu Asn Glu Asp Leu Thr Cys Gly Asn Leu Leu Met Trp Glu 100 105 110 Ala Val Thr Val Gln Thr Glu Val Ile Gly Ile Thr Ser Met Leu Asn 115 120 125 Leu His Ala Gly Ser Gln Lys Val His Glu His Gly Gly Gly Lys Pro 130 135 140 Ile Gln Gly Ser Asn Phe His Phe Phe Ala Val Gly Gly Asp Pro Leu 145 150 155 160 Glu Met Gln Gly Val Leu Met Asn Tyr Arg Thr Lys Tyr Pro Asp Gly 165 170 175 Thr Ile Thr Pro Lys Asn Pro Thr Ala Gln Ser Gln Val Met Asn Thr 180 185 190 Asp His Lys Ala Tyr Leu Asp Lys Asn Asn Ala Tyr Pro Val Glu Cys 195 200 205 Trp Val Pro Asp Pro Ser Arg Asn Glu Asn Thr Arg Tyr Phe Gly Thr 210 215 220 Phe Thr Gly Gly Glu Asn Val Pro Pro Val Leu His Val Thr Asn Thr 225 230 235 240 Ala Thr Thr Val Leu Leu Asp Glu Gln Gly Val Gly Pro Leu Cys Lys 245 250 255 Ala Asp Ser Leu Tyr Val Ser Ala Ala Asp Ile Cys Gly Leu Phe Thr 260 265 270 Asn Ser Ser Gly Thr Gln Gln Trp Arg Gly Leu Ala Arg Tyr Phe Lys 275 280 285 Ile Arg Leu Arg Lys Arg Ser Val Lys Asn Pro Tyr Pro Ile Ser Phe 290 295 300 Leu Leu Ser Asp Leu Ile Thr Arg Arg Thr Gln Arg Val Asp Gly Gln 305 310 315 320 Pro Met Tyr Gly Met Glu Ser Gln Val Glu Glu Val Arg Val Phe Asp 325 330 335 Gly Thr Glu Arg Leu Pro Gly Asp Pro Asp Met Ile Arg Tyr Ile Asp 340 345 350 Lys Gln Gly Gln Leu Gln Thr Lys Met Leu 355 360 62362PRTBK virus 62Met Ala Pro Thr Lys Arg Lys Gly Glu Cys Pro Gly Ala Ala Pro Lys 1 5 10 15 Lys Pro Lys Glu Pro Val Gln Val Pro Lys Leu Leu Ile Lys Gly Gly 20 25 30 Val Glu Val Leu Glu Val Lys Thr Gly Val Asp Ala Ile Thr Glu Val 35 40 45 Glu Cys Phe Leu Asn Pro Glu Met Gly Asp Pro Asp Glu Asn Leu Arg 50 55 60 Gly Phe Ser Leu Lys Leu Ser Ala Glu Asn Asp Phe Ser Ser Asp Ser 65 70 75 80 Pro Glu Arg Lys Met Leu Pro Cys Tyr Ser Thr Ala Arg Ile Pro Leu 85 90 95 Pro Asn Leu Asn Glu Asp Leu Thr Cys Gly Asn Leu Leu Met Trp Glu 100 105 110 Ala Val Thr Val Gln Thr Glu Val Ile Gly Ile Thr Ser Met Leu Asn 115 120 125 Leu His Ala Gly Ser Gln Lys Val His Glu His Gly Gly Gly Lys Pro 130 135 140 Ile Gln Gly Ser Asn Phe His Phe Phe Ala Val Gly Gly Glu Pro Leu 145 150 155 160 Glu Met Gln Gly Val Leu Met Asn Tyr Arg Ser Lys Tyr Pro Asp Gly 165 170 175 Thr Ile Thr Pro Lys Asn Pro Thr Ala Gln Ser Gln Val Met Asn Thr 180 185 190 Asp His Lys Ala Tyr Leu Asp Lys Asn Asn Ala Tyr Pro Val Glu Cys 195 200 205 Trp Val Pro Asp Pro Ser Arg Asn Glu Asn Ala Arg Tyr Phe Gly Thr 210 215 220 Phe Thr Gly Gly Glu Asn Val Pro Pro Val Leu His Val Thr Asn Thr 225 230 235 240 Ala Thr Thr Val Leu Leu Asp Glu Gln Gly Val Gly Pro Leu Cys Lys 245 250 255 Ala Asp Ser Leu Tyr Val Ser Ala Ala Asp Ile Cys Gly Leu Phe Thr 260 265 270 Asn Ser Ser Gly Thr Gln Gln Trp Arg Gly Leu Ala Arg Tyr Phe Lys 275 280 285 Ile Arg Leu Arg Lys Arg Ser Val Lys Asn Pro Tyr Pro Ile Ser Phe 290 295 300 Leu Leu Ser Asp Leu Ile Asn Arg Arg Thr Gln Arg Val Asp Gly Gln 305 310 315 320 Pro Met Tyr Gly Met Glu Ser Gln Val Glu Glu Val Arg Val Phe Asp 325 330 335 Gly Thr Glu Arg Leu Pro Gly Asp Pro Asp Met Ile Arg Tyr Ile Asp 340 345 350 Lys Gln Gly Gln Leu Gln Thr Lys Met Leu 355 360 63362PRTBK virus 63Met Ala Pro Ala Lys Arg Lys Gly Glu Cys Pro Gly Ala Ala Pro Lys 1 5 10 15 Lys Pro Lys Glu Pro Val Gln Val Pro Lys Leu Leu Ile Lys Gly Gly 20 25 30 Val Glu Val Leu Glu Val Lys Thr Gly Val Asp Ala Ile Thr Glu Val 35 40 45 Glu Cys Phe Leu Asn Pro Glu Met Gly Asp Pro Asp Glu Asn Leu Arg 50 55 60 Gly Phe Ser Leu Lys Leu Ser Ala Glu Asn Asp Phe Ser Ser Asp Ser 65 70 75 80 Pro Glu Arg Lys Met Leu Pro Cys Tyr Ser Thr Ala Arg Ile Pro Leu 85 90 95 Pro Asn Leu Asn Glu Asp Leu Thr Cys Gly Asn Leu Leu Met Trp Glu 100 105 110 Ala Val Thr Val Gln Thr Glu Val Ile Gly Ile Thr Ser Met Leu Asn 115 120 125 Leu His Ala Gly Ser Gln Lys Val His Glu His Gly Gly Gly Lys Pro 130 135

140 Ile Gln Gly Ser Asn Phe His Phe Phe Ala Val Gly Gly Asp Pro Leu 145 150 155 160 Glu Met Gln Gly Val Leu Met Asn Tyr Arg Thr Lys Tyr Pro Asp Gly 165 170 175 Thr Ile Thr Pro Lys Asn Pro Thr Ala Gln Ser Gln Val Met Asn Thr 180 185 190 Asp His Lys Ala Tyr Leu Asp Lys Asn Asn Ala Tyr Pro Val Glu Cys 195 200 205 Trp Val Pro Asp Pro Ser Arg Asn Glu Asn Thr Arg Tyr Phe Gly Thr 210 215 220 Phe Thr Gly Gly Glu Asn Val Pro Pro Val Leu His Val Thr Asn Thr 225 230 235 240 Ala Thr Thr Val Leu Leu Asp Glu Gln Gly Val Gly Pro Leu Cys Lys 245 250 255 Ala Asp Ser Leu Tyr Val Ser Ala Ala Asp Ile Cys Gly Leu Phe Thr 260 265 270 Asn Ser Ser Gly Thr Gln Gln Trp Arg Gly Leu Ala Arg Tyr Phe Arg 275 280 285 Ile Arg Leu Arg Lys Arg Ser Val Lys Asn Pro Tyr Pro Ile Ser Phe 290 295 300 Leu Leu Ser Asp Leu Ile Asn Arg Arg Thr Gln Arg Val Asp Gly Gln 305 310 315 320 Pro Met Tyr Gly Met Glu Ser Gln Val Gly Glu Val Arg Val Phe Asp 325 330 335 Gly Thr Glu Arg Leu Pro Gly Asp Pro Asp Met Ile Arg Tyr Ile Asp 340 345 350 Lys Gln Gly Gln Leu Gln Thr Lys Met Leu 355 360 64362PRTBK virus 64Met Ala Pro Thr Lys Arg Lys Gly Glu Cys Pro Gly Ala Ala Pro Lys 1 5 10 15 Lys Pro Lys Glu Pro Val Gln Val Pro Lys Leu Leu Ile Lys Gly Gly 20 25 30 Val Glu Val Leu Glu Val Lys Thr Gly Val Asp Ala Ile Thr Glu Val 35 40 45 Glu Cys Phe Leu Asn Pro Glu Met Gly Asp Pro Asp Glu Asn Leu Arg 50 55 60 Gly Phe Ser Leu Lys Leu Ser Ala Glu Asn Asp Phe Ser Ser Asp Ser 65 70 75 80 Pro Glu Arg Lys Met Leu Pro Cys Tyr Ser Thr Ala Arg Ile Pro Leu 85 90 95 Pro Asn Leu Asn Glu Asp Leu Thr Cys Gly Asn Leu Leu Met Trp Glu 100 105 110 Ala Val Thr Val Gln Thr Glu Val Ile Gly Ile Thr Ser Met Leu Asn 115 120 125 Leu His Ala Gly Ser Gln Lys Val His Glu His Gly Gly Gly Lys Pro 130 135 140 Ile Gln Gly Ser Asn Phe His Phe Phe Ala Val Gly Gly Asp Pro Leu 145 150 155 160 Glu Met Gln Gly Val Leu Met Asn Tyr Arg Thr Lys Tyr Pro Asp Gly 165 170 175 Thr Ile Thr Pro Lys Asn Pro Thr Ala Gln Ser Gln Val Met Asn Thr 180 185 190 Asp His Lys Ala Tyr Leu Asp Lys Asn Asn Ala Tyr Pro Val Glu Cys 195 200 205 Trp Val Pro Asp Pro Ser Arg Asn Glu Asn Thr Arg Tyr Phe Gly Thr 210 215 220 Phe Thr Gly Gly Glu Asn Val Pro Pro Val Leu His Val Thr Asn Thr 225 230 235 240 Ala Thr Thr Val Leu Leu Asp Glu Gln Gly Val Gly Pro Leu Cys Lys 245 250 255 Ala Asp Ser Leu Tyr Val Ser Ala Ala Asp Ile Cys Gly Leu Phe Thr 260 265 270 Asn Ser Ser Gly Thr Gln Gln Trp Arg Gly Leu Ala Arg Tyr Phe Lys 275 280 285 Ile Arg Leu Arg Lys Arg Ser Val Lys Asn Pro Tyr Leu Ile Ser Phe 290 295 300 Leu Leu Ser Asp Leu Ile Asn Arg Arg Thr Gln Arg Val Asp Gly Gln 305 310 315 320 Pro Met Tyr Gly Met Glu Ser Gln Val Glu Glu Val Arg Val Phe Asp 325 330 335 Gly Thr Glu Arg Leu Pro Gly Asp Pro Asp Met Ile Arg Tyr Ile Asp 340 345 350 Lys Gln Gly Gln Leu Gln Thr Lys Met Leu 355 360 65362PRTBK virus 65Met Ala Pro Thr Lys Arg Lys Gly Glu Cys Pro Gly Ala Ala Pro Lys 1 5 10 15 Lys Pro Lys Glu Pro Val Gln Val Pro Lys Leu Leu Ile Lys Gly Gly 20 25 30 Val Glu Val Leu Glu Val Lys Thr Gly Val Asp Ala Ile Thr Glu Val 35 40 45 Glu Cys Phe Leu Asn Pro Glu Met Gly Asp Pro Asp Glu Asn Leu Arg 50 55 60 Gly Phe Ser Leu Lys Leu Ser Ala Glu Asn Asp Phe Ser Ser Asp Ser 65 70 75 80 Pro Glu Arg Lys Met Leu Pro Cys Tyr Ser Thr Ala Arg Ile Pro Leu 85 90 95 Pro Asn Leu Asn Glu Asp Leu Thr Cys Gly Asn Leu Leu Met Trp Glu 100 105 110 Ala Val Thr Val Gln Thr Glu Val Thr Gly Ile Thr Ser Met Leu Asn 115 120 125 Leu His Ala Gly Ser Gln Lys Val His Glu His Gly Gly Gly Lys Pro 130 135 140 Ile Gln Gly Ser Asn Phe His Phe Phe Ala Val Gly Gly Asp Pro Leu 145 150 155 160 Glu Met Gln Gly Val Leu Met Asn Tyr Arg Thr Lys Tyr Pro Asp Gly 165 170 175 Thr Ile Thr Pro Lys Asn Pro Thr Ala Gln Ser Gln Val Met Asn Thr 180 185 190 Asp His Lys Ala Tyr Leu Asp Lys Asn Asn Ala Tyr Pro Val Glu Cys 195 200 205 Trp Val Pro Asp Pro Ser Arg Asn Glu Asn Thr Arg Tyr Phe Gly Thr 210 215 220 Phe Thr Gly Gly Glu Asn Val Pro Pro Val Leu His Val Thr Asn Thr 225 230 235 240 Ala Thr Thr Val Leu Leu Asp Glu Gln Gly Val Gly Pro Leu Cys Lys 245 250 255 Ala Asp Gly Leu Tyr Val Ser Ala Ala Asp Ile Cys Gly Leu Phe Thr 260 265 270 Asn Ser Ser Gly Thr Gln Gln Trp Arg Gly Leu Ala Arg Tyr Phe Lys 275 280 285 Thr Arg Leu Arg Lys Arg Ser Val Lys Asn Pro Tyr Pro Ile Ser Ser 290 295 300 Leu Leu Ser Asp Leu Ile Asn Arg Arg Thr Gln Arg Val Asp Gly Gln 305 310 315 320 Pro Met Tyr Gly Met Glu Ser Gln Val Glu Glu Val Arg Val Phe Asp 325 330 335 Gly Thr Glu Arg Leu Pro Gly Asp Pro Asp Met Ile Arg Tyr Ile Asp 340 345 350 Lys Gln Gly Gln Leu Gln Thr Lys Met Leu 355 360 66362PRTBK virus 66Met Ala Pro Thr Lys Arg Lys Gly Glu Cys Pro Gly Ala Ala Pro Lys 1 5 10 15 Lys Pro Lys Glu Pro Val Gln Val Pro Lys Leu Leu Ile Lys Gly Gly 20 25 30 Val Glu Val Leu Glu Val Lys Thr Gly Val Asp Ala Ile Thr Gln Val 35 40 45 Glu Cys Phe Leu Asn Pro Glu Met Gly Asp Pro Asp Glu Asn Leu Arg 50 55 60 Gly Phe Ser Leu Lys Leu Ser Ala Glu Asn Asp Phe Ser Ser Asp Ser 65 70 75 80 Pro Glu Arg Lys Met Leu Pro Cys Tyr Ser Thr Ala Arg Ile Pro Leu 85 90 95 Pro Asn Leu Asn Glu Asp Leu Thr Cys Gly Asn Leu Leu Met Trp Glu 100 105 110 Ala Val Thr Val Gln Thr Glu Val Ile Gly Ile Thr Ser Met Leu Asn 115 120 125 Leu His Ala Gly Ser Gln Lys Val His Glu His Gly Gly Gly Lys Pro 130 135 140 Ile Arg Gly Ser Asn Phe His Phe Phe Ala Val Gly Gly Asp Pro Leu 145 150 155 160 Glu Met Gln Gly Val Leu Met Asn Tyr Arg Thr Lys Tyr Pro Glu Gly 165 170 175 Thr Ile Thr Pro Lys Asn Pro Thr Ala Gln Ser Gln Val Met Asn Thr 180 185 190 Asp His Lys Ala Tyr Leu Asp Lys Asn Asn Ala Tyr Pro Val Glu Cys 195 200 205 Trp Val Pro Asp Pro Ser Arg Asn Glu Asn Thr Arg Tyr Phe Gly Thr 210 215 220 Phe Thr Gly Gly Glu Asn Val Pro Pro Val Leu His Val Thr Asn Thr 225 230 235 240 Ala Thr Thr Val Leu Leu Asp Glu Gln Gly Val Gly Pro Leu Cys Lys 245 250 255 Ala Asp Ser Leu Tyr Val Ser Ala Ala Asp Ile Cys Gly Leu Phe Thr 260 265 270 Asn Ser Ser Gly Thr Gln Gln Trp Arg Gly Leu Ala Arg Tyr Phe Lys 275 280 285 Ile Arg Leu Arg Lys Arg Ser Val Lys Asn Pro Tyr Pro Ile Ser Phe 290 295 300 Ser Leu Ser Asp Leu Ile Asn Arg Arg Thr Gln Arg Val Asp Gly Gln 305 310 315 320 Pro Met Tyr Gly Met Glu Ser Gln Val Glu Glu Val Arg Val Phe Asp 325 330 335 Gly Thr Glu Arg Leu Pro Gly Asp Pro Asp Met Ile Arg Tyr Ile Asp 340 345 350 Lys Gln Gly Gln Leu Gln Thr Lys Met Leu 355 360 67362PRTBK virus 67Met Ala Pro Thr Lys Arg Lys Gly Glu Cys Pro Gly Ala Ala Pro Lys 1 5 10 15 Lys Pro Lys Glu Pro Val Gln Val Pro Lys Leu Leu Ile Lys Gly Gly 20 25 30 Val Glu Val Leu Glu Val Lys Thr Gly Val Asp Ala Ile Thr Glu Val 35 40 45 Glu Cys Phe Leu Asn Pro Glu Met Gly Asp Pro Asp Glu Asn Leu Arg 50 55 60 Gly Phe Ser Leu Lys Leu Ser Ala Glu Asn Asp Phe Ser Ser Asp Ser 65 70 75 80 Pro Glu Arg Lys Met Leu Pro Cys Tyr Ser Thr Ala Arg Ile Pro Leu 85 90 95 Pro Asn Leu Asn Glu Asp Leu Thr Cys Gly Asn Leu Leu Met Trp Glu 100 105 110 Ala Val Thr Val Gln Thr Glu Val Ile Gly Ile Thr Ser Met Leu Asn 115 120 125 Leu His Ala Gly Ser Gln Lys Val His Glu His Gly Gly Gly Lys Pro 130 135 140 Ile Gln Gly Ser Asn Phe His Phe Phe Ala Val Gly Gly Asp Pro Leu 145 150 155 160 Glu Met Gln Gly Val Leu Met Asn Tyr Arg Thr Lys Tyr Pro Glu Gly 165 170 175 Thr Ile Thr Pro Lys Asn Pro Thr Ala Gln Ser Gln Val Met Asn Thr 180 185 190 Asp His Lys Ala Tyr Leu Asp Lys Asn Asn Ala Tyr Pro Val Glu Cys 195 200 205 Trp Val Pro Asp Pro Ser Arg Asn Glu Asn Thr Arg Tyr Phe Gly Thr 210 215 220 Phe Thr Gly Gly Glu Asn Val Pro Pro Val Leu His Val Thr Asn Thr 225 230 235 240 Ala Thr Thr Val Leu Leu Asp Glu Gln Gly Val Gly Pro Leu Cys Lys 245 250 255 Ala Asp Ser Leu Tyr Val Ser Ala Ala Asp Ile Cys Gly Leu Phe Thr 260 265 270 Asn Ser Ser Gly Thr Gln Gln Trp Arg Gly Leu Ala Arg Tyr Phe Lys 275 280 285 Ile Arg Leu Arg Lys Arg Ser Val Lys Asn Pro Tyr Pro Ile Ser Phe 290 295 300 Leu Leu Ser Asp Leu Ile Asn Arg Arg Thr Gln Arg Val Asp Gly Gln 305 310 315 320 Pro Met Tyr Gly Met Glu Ser Gln Val Glu Glu Val Arg Val Phe Asp 325 330 335 Gly Thr Glu Arg Leu Pro Gly Asp Pro Asp Met Ile Arg Tyr Ile Asp 340 345 350 Lys Gln Gly Gln Leu Gln Thr Lys Met Leu 355 360 68362PRTBK virus 68Met Ala Pro Thr Lys Arg Lys Gly Glu Cys Pro Gly Ala Ala Pro Lys 1 5 10 15 Lys Pro Lys Glu Pro Val Gln Val Pro Lys Leu Leu Ile Lys Gly Gly 20 25 30 Val Glu Val Leu Glu Val Lys Thr Gly Val Asp Ala Ile Thr Glu Val 35 40 45 Glu Cys Phe Leu Asn Pro Glu Met Gly Asp Pro Asp Glu Asn Leu Arg 50 55 60 Gly Phe Ser Leu Lys Leu Ser Ala Glu Tyr Asp Phe Ser Ser Asp Ser 65 70 75 80 Pro Glu Arg Lys Met Leu Pro Cys Tyr Ser Thr Ala Arg Ile Pro Leu 85 90 95 Pro Asn Leu Tyr Glu Asp Leu Thr Cys Gly Asn Leu Leu Met Trp Glu 100 105 110 Ala Val Thr Val Gln Thr Glu Val Ile Gly Ile Thr Ser Met Leu Asn 115 120 125 Leu His Ala Gly Ser Gln Lys Val His Glu His Gly Gly Gly Lys Pro 130 135 140 Ile Gln Gly Ser Asn Phe His Phe Phe Ala Val Gly Gly Asp Pro Leu 145 150 155 160 Glu Met Gln Gly Val Leu Met Asn Tyr Arg Thr Lys Tyr Pro Asp Gly 165 170 175 Thr Ile Thr Pro Lys Asn Pro Thr Ala Gln Ser Gln Val Met Asn Thr 180 185 190 Asp His Lys Ala Tyr Leu Asp Lys Asn Asn Ala Tyr Pro Val Glu Cys 195 200 205 Trp Val Pro Asp Pro Ser Arg Asn Glu Asn Thr Arg Tyr Phe Gly Thr 210 215 220 Phe Thr Gly Gly Glu Asn Val Pro Pro Val Leu His Val Thr Asn Thr 225 230 235 240 Ala Thr Thr Val Leu Leu Asp Glu Gln Gly Val Gly Pro Leu Cys Lys 245 250 255 Ala Asp Ser Leu Tyr Val Ser Ala Ala Asp Ile Cys Gly Leu Phe Thr 260 265 270 Asn Ser Ser Gly Thr Gln Gln Trp Arg Gly Leu Ala Arg Tyr Phe Lys 275 280 285 Ile Arg Leu Arg Lys Arg Ser Val Lys Asn Pro Tyr Pro Ile Ser Phe 290 295 300 Leu Leu Ser Asp Leu Ile Asn Arg Arg Thr Gln Arg Val Asp Gly Gln 305 310 315 320 Pro Met Tyr Gly Met Glu Ser Gln Val Glu Glu Val Arg Val Phe Asp 325 330 335 Gly Thr Glu Arg Leu Pro Gly Asp Pro Asp Met Ile Arg Tyr Ile Asp 340 345 350 Lys Gln Gly Gln Leu Gln Thr Lys Met Leu 355 360 69362PRTBK virus 69Met Ala Pro Thr Lys Arg Lys Gly Glu Cys Pro Gly Ala Ala Pro Lys 1 5 10 15 Lys Pro Lys Glu Pro Val Gln Val Pro Lys Leu Leu Ile Lys Gly Gly 20 25 30 Val Glu Val Leu Glu Val Lys Thr Gly Val Asp Ala Ile Thr Glu Val 35 40 45 Glu Cys Phe Leu Asn Pro Glu Met Gly Asp Pro Asn Glu Asn Leu Arg 50 55 60 Gly Phe Ser Leu Met Leu Ser Ala Glu Asn Asp Phe Asn Ser Asp Ser 65 70 75 80 Pro Glu Arg Lys Met Leu Pro Cys Tyr Ser Thr Ala Arg Ile Pro Leu 85 90 95 Pro Asn Leu Asn Glu Asp Leu Thr Cys Gly Asn Leu Leu Met Trp Glu 100 105 110 Ala Val Thr Val Gln Thr Glu Val Ile Gly Ile Thr Ser Met Leu Asn 115 120 125 Leu His Ala Gly Ser Gln Lys Val His Glu His Gly Gly Gly Lys Pro 130 135 140 Ile Gln Gly Ser Asn Phe His Phe Phe Ala Val Gly Gly Asp Pro Leu 145 150 155 160 Glu Met Gln Gly Val Leu Met Asn Tyr Arg Thr Lys Tyr Pro Asp Gly 165 170 175 Thr Ile Thr Pro Lys Asn Pro Thr Ala Gln Ser Gln Val Met Asn Thr 180 185 190 Asp His Lys Ala Tyr Leu Asp Lys Asn Asn Ala Tyr Pro Val Glu Cys 195 200 205 Trp Val Pro Asp Pro Ser Arg Asn Glu Asn Thr Arg Tyr Phe Gly Thr 210 215 220 Phe Thr Gly Gly Glu Asn Val Pro Pro Val Leu His Val Thr Asn Thr 225 230 235 240 Ala Thr Thr Val Leu Leu Asp Glu Gln Gly Val Gly Pro Leu Cys Lys 245 250 255 Ala Asp Ser Leu Tyr Val Ser Ala Ala

Asp Ile Cys Gly Leu Phe Thr 260 265 270 Asn Ser Ser Gly Thr Gln Gln Trp Arg Gly Leu Ala Arg Tyr Phe Lys 275 280 285 Ile Arg Leu Arg Lys Arg Ser Val Lys Asn Pro Tyr Pro Ile Ser Phe 290 295 300 Leu Leu Ser Asp Leu Ile Asn Arg Arg Thr Gln Arg Val Asp Gly Gln 305 310 315 320 Pro Met Tyr Gly Met Glu Ser Gln Val Glu Glu Val Arg Val Phe Asp 325 330 335 Gly Thr Glu Arg Leu Pro Gly Asp Pro Asp Met Ile Arg Tyr Ile Asp 340 345 350 Lys Gln Gly Gln Leu Gln Thr Lys Met Leu 355 360 70362PRTBK virus 70Met Ala Pro Thr Lys Arg Lys Gly Glu Cys Pro Gly Ala Ala Pro Lys 1 5 10 15 Lys Pro Lys Glu Pro Val Gln Val Pro Lys Leu Leu Ile Lys Gly Gly 20 25 30 Val Glu Val Leu Glu Val Lys Thr Gly Val Asp Ala Ile Thr Glu Val 35 40 45 Glu Cys Phe Leu Asn Pro Glu Met Gly Asp Pro Asn Glu Asn Leu Arg 50 55 60 Gly Phe Ser Leu Lys Leu Ser Ala Glu Asn Asp Phe Ser Ser Asp Ser 65 70 75 80 Pro Glu Arg Lys Met Leu Pro Cys Tyr Ser Thr Ala Arg Ile Pro Leu 85 90 95 Pro Asn Leu Asn Glu Asp Leu Thr Cys Gly Asn Leu Leu Met Trp Glu 100 105 110 Ala Val Thr Val Gln Thr Glu Val Ile Gly Ile Thr Ser Met Leu Asn 115 120 125 Leu His Ala Gly Ser Gln Lys Val His Glu His Gly Gly Gly Lys Pro 130 135 140 Ile Gln Gly Ser Asn Phe His Phe Phe Ala Val Gly Gly Asp Pro Leu 145 150 155 160 Glu Met Gln Gly Val Leu Met Asn Tyr Arg Thr Lys Tyr Pro Asp Gly 165 170 175 Thr Ile Thr Pro Lys Asn Pro Thr Ala Gln Ser Gln Val Met Asn Thr 180 185 190 Asp His Lys Ala Tyr Leu Asp Lys Asn Asn Ala Tyr Pro Val Glu Cys 195 200 205 Trp Val Pro Asp Pro Ser Arg Asn Glu Asn Thr Arg Tyr Phe Gly Thr 210 215 220 Phe Thr Gly Gly Glu Asn Val Pro Pro Val Leu His Val Thr Asn Thr 225 230 235 240 Ala Thr Thr Val Leu Leu Asp Glu Gln Gly Val Gly Pro Leu Cys Lys 245 250 255 Ala Asp Ser Leu Tyr Val Ser Ala Ala Asp Ile Cys Gly Leu Phe Thr 260 265 270 Asn Ser Ser Gly Thr Gln Gln Trp Arg Gly Leu Ala Arg Tyr Phe Lys 275 280 285 Ile Arg Leu Arg Lys Arg Ser Val Lys Asn Pro Tyr Pro Ile Ser Phe 290 295 300 Leu Leu Ser Asp Leu Ile Asn Arg Arg Thr Gln Arg Val Asp Gly Gln 305 310 315 320 Pro Met Tyr Gly Met Glu Ser Gln Val Glu Glu Val Arg Val Phe Asp 325 330 335 Gly Thr Glu Arg Leu Pro Gly Asp Pro Asp Met Ile Arg Tyr Ile Asp 340 345 350 Lys Gln Gly Gln Leu Gln Thr Lys Met Leu 355 360 71362PRTBK virus 71Met Ala Pro Thr Lys Arg Lys Gly Glu Cys Pro Gly Ala Ala Pro Lys 1 5 10 15 Lys Pro Lys Glu Pro Val Gln Val Pro Lys Leu Leu Ile Lys Gly Gly 20 25 30 Val Glu Val Leu Glu Val Lys Thr Gly Val Asp Ala Ile Thr Glu Val 35 40 45 Glu Cys Phe Leu Asn Pro Glu Met Gly Asp Pro Asp Glu Asn Leu Arg 50 55 60 Gly Phe Ser Leu Lys Leu Ser Ala Gln Asn Asp Phe Ser Ser Asp Ser 65 70 75 80 Pro Glu Arg Lys Met Leu Pro Cys Tyr Ser Thr Ala Arg Ile Pro Leu 85 90 95 Pro Asn Leu Asn Glu Asp Leu Thr Cys Gly Asn Leu Leu Met Trp Glu 100 105 110 Ala Val Thr Val Gln Thr Glu Val Ile Gly Ile Thr Ser Met Leu Asn 115 120 125 Leu His Ala Gly Ser Gln Lys Val His Glu His Gly Gly Gly Lys Pro 130 135 140 Ile Gln Gly Ser Asn Phe His Phe Phe Ala Val Gly Gly Asp Pro Leu 145 150 155 160 Glu Met Gln Gly Val Leu Met Asn Tyr Arg Thr Lys Tyr Pro Glu Gly 165 170 175 Thr Ile Thr Pro Lys Asn Pro Thr Ala Gln Ser Gln Val Met Asn Thr 180 185 190 Asp His Lys Ala Tyr Leu Asp Lys Asn Asn Ala Tyr Pro Val Glu Cys 195 200 205 Trp Val Pro Asp Pro Ser Arg Asn Glu Asn Thr Arg Tyr Phe Gly Thr 210 215 220 Phe Thr Gly Gly Glu Asn Val Pro Pro Val Leu His Val Thr Asn Thr 225 230 235 240 Ala Thr Thr Val Leu Leu Asp Glu Gln Gly Val Gly Pro Leu Cys Lys 245 250 255 Ala Asp Ser Leu Tyr Val Ser Ala Ala Asp Ile Cys Gly Leu Phe Thr 260 265 270 Asn Ser Ser Gly Thr Gln Gln Trp Arg Gly Leu Ala Arg Tyr Phe Lys 275 280 285 Ile Arg Leu Arg Lys Arg Ser Val Lys Asn Pro Tyr Pro Ile Ser Phe 290 295 300 Leu Leu Ser Asp Leu Ile Asn Arg Arg Thr Gln Arg Val Asp Gly Gln 305 310 315 320 Pro Met Tyr Gly Met Glu Ser Gln Val Glu Glu Val Arg Val Phe Asp 325 330 335 Gly Thr Glu Arg Leu Pro Gly Asp Pro Asp Met Ile Arg Tyr Ile Asp 340 345 350 Lys Gln Gly Gln Leu Gln Thr Lys Met Leu 355 360 72362PRTBK virus 72Met Ala Pro Thr Lys Arg Lys Gly Glu Cys Pro Gly Ala Ala Pro Lys 1 5 10 15 Lys Pro Lys Glu Pro Val Gln Val Pro Lys Leu Leu Ile Lys Gly Gly 20 25 30 Val Glu Val Leu Glu Val Lys Thr Gly Val Asp Ala Ile Thr Glu Val 35 40 45 Glu Cys Phe Leu Asn Pro Glu Met Gly Asp Pro Asp Glu Asn Leu Arg 50 55 60 Gly Phe Ser Leu Lys Leu Ser Ala Gln Asn Asp Phe Ser Ser Asp Ser 65 70 75 80 Pro Glu Arg Lys Met Leu Pro Cys Tyr Ser Thr Ala Arg Ile Pro Leu 85 90 95 Pro Asn Leu Asn Glu Asp Leu Thr Cys Gly Asn Leu Leu Met Trp Glu 100 105 110 Ala Val Thr Val Gln Thr Glu Val Ile Gly Ile Thr Ser Met Leu Asn 115 120 125 Leu His Ala Gly Ser Gln Lys Val His Glu His Gly Gly Gly Lys Pro 130 135 140 Ile Gln Gly Ser Asn Phe His Phe Phe Ala Val Gly Gly Asp Pro Leu 145 150 155 160 Glu Met Gln Gly Val Leu Met Asn Tyr Trp Thr Lys Tyr Pro Glu Gly 165 170 175 Thr Ile Thr Pro Lys Asn Pro Thr Ala Gln Ser Gln Val Met Asn Thr 180 185 190 Asp His Lys Ala Tyr Leu Asp Lys Asn Asn Ala Tyr Pro Val Glu Cys 195 200 205 Trp Val Pro Asp Pro Ser Arg Asn Glu Asn Thr Arg Tyr Phe Gly Thr 210 215 220 Phe Thr Gly Gly Glu Asn Val Pro Pro Val Leu His Val Thr Asn Thr 225 230 235 240 Ala Thr Thr Val Leu Leu Asp Glu Gln Gly Val Gly Pro Leu Cys Lys 245 250 255 Ala Asp Ser Leu Tyr Val Ser Ala Ala Asp Ile Cys Gly Leu Phe Thr 260 265 270 Asn Ser Ser Gly Thr Gln Gln Trp Arg Gly Leu Ala Arg Tyr Phe Lys 275 280 285 Ile Arg Leu Arg Lys Arg Ser Val Lys Asn Pro Tyr Pro Ile Ser Phe 290 295 300 Leu Leu Ser Asp Leu Ile Asn Arg Arg Thr Gln Arg Val Asp Gly Gln 305 310 315 320 Pro Met Tyr Gly Met Glu Ser Gln Val Glu Glu Val Arg Val Phe Asp 325 330 335 Gly Thr Glu Arg Leu Pro Gly Asp Pro Asp Met Ile Arg Tyr Ile Asp 340 345 350 Lys Gln Gly Gln Leu Gln Thr Lys Met Leu 355 360 73362PRTBK virus 73Met Ala Pro Thr Lys Arg Lys Gly Glu Cys Pro Gly Ala Ala Pro Lys 1 5 10 15 Lys Pro Lys Glu Pro Val Gln Val Pro Lys Leu Leu Ile Lys Gly Gly 20 25 30 Val Glu Val Leu Glu Val Lys Thr Gly Val Asp Ala Ile Thr Glu Val 35 40 45 Glu Cys Phe Leu Asn Pro Glu Met Gly Asp Pro Asp Glu Asn Leu Arg 50 55 60 Gly Phe Ser Leu Lys Leu Ser Ala Lys Asn Asp Phe Ser Ser Asp Ser 65 70 75 80 Pro Glu Arg Lys Met Leu Pro Cys Tyr Ser Thr Ala Arg Ile Pro Leu 85 90 95 Pro Asn Leu Asn Glu Asp Leu Thr Cys Gly Asn Leu Leu Met Trp Glu 100 105 110 Ala Val Thr Val Gln Thr Glu Val Ile Gly Ile Thr Ser Met Leu Asn 115 120 125 Leu His Ala Gly Ser Gln Lys Val His Glu His Gly Gly Gly Lys Pro 130 135 140 Ile Gln Gly Ser Asn Phe His Phe Phe Ala Val Gly Gly Asp Pro Leu 145 150 155 160 Glu Met Gln Gly Val Leu Met Asn Tyr Arg Thr Lys Tyr Pro Asp Gly 165 170 175 Thr Ile Thr Pro Lys Asn Pro Thr Ala Gln Ser Gln Val Met Asn Thr 180 185 190 Asp His Lys Ala Tyr Leu Asp Lys Asn Asn Ala Tyr Pro Val Glu Cys 195 200 205 Trp Val Pro Asp Pro Ser Arg Asn Glu Asn Thr Arg Tyr Phe Gly Thr 210 215 220 Phe Thr Gly Gly Glu Asn Val Pro Pro Val Leu His Val Thr Asn Thr 225 230 235 240 Ala Thr Thr Val Leu Leu Asp Glu Gln Gly Val Gly Pro Leu Cys Lys 245 250 255 Ala Asp Ser Leu Tyr Val Ser Ala Ala Asp Ile Cys Gly Leu Phe Thr 260 265 270 Asn Ser Ser Gly Thr Gln Gln Trp Arg Gly Leu Ala Arg Tyr Phe Lys 275 280 285 Ile Arg Leu Arg Lys Arg Ser Val Lys Asn Pro Tyr Pro Ile Ser Phe 290 295 300 Leu Leu Ser Asp Leu Ile Asn Arg Arg Thr Gln Arg Val Asp Gly Gln 305 310 315 320 Pro Met Tyr Gly Met Glu Ser Gln Val Glu Glu Val Arg Val Phe Asp 325 330 335 Gly Thr Glu Arg Leu Pro Gly Asp Pro Asp Met Ile Arg Tyr Ile Asp 340 345 350 Lys Gln Gly Gln Leu Gln Thr Lys Met Leu 355 360 74362PRTBK virus 74Met Ala Pro Thr Lys Arg Lys Gly Glu Cys Pro Gly Ala Ala Pro Lys 1 5 10 15 Lys Pro Lys Glu Pro Val Gln Val Pro Lys Leu Leu Ile Lys Gly Gly 20 25 30 Val Glu Val Leu Glu Val Lys Thr Gly Val Asp Ala Ile Thr Glu Val 35 40 45 Glu Cys Phe Leu Asn Pro Glu Met Gly Asp Pro Asp Glu Asn Leu Arg 50 55 60 Gly Phe Ser Leu Lys Leu Ser Ala Glu Asn Asp Phe Ser Ser Asp Ser 65 70 75 80 Pro Glu Arg Lys Met Leu Pro Cys Tyr Ser Thr Ala Arg Ile Pro Leu 85 90 95 Pro Asn Leu Asn Glu Asp Leu Thr Cys Gly Asn Leu Leu Met Trp Glu 100 105 110 Ala Val Thr Val Gln Thr Glu Val Ile Gly Ile Thr Ser Met Leu Asn 115 120 125 Leu His Ala Gly Ser Gln Lys Val His Glu His Gly Gly Gly Lys Pro 130 135 140 Ile Gln Gly Ser Asn Phe His Phe Phe Ala Val Gly Gly Asp Pro Leu 145 150 155 160 Glu Met Gln Gly Val Leu Met Asn Tyr Arg Thr Lys Tyr Pro Asp Gly 165 170 175 Thr Ile Thr Pro Lys Asn Pro Thr Ala Gln Ser Gln Val Met Asn Thr 180 185 190 Asp His Lys Ala Tyr Leu Asp Lys Asn Asn Ala Tyr Pro Val Glu Cys 195 200 205 Trp Val Pro Asp Pro Ser Arg Asn Glu Asn Thr Arg Tyr Phe Gly Thr 210 215 220 Phe Thr Gly Gly Glu Asn Val Pro Pro Val Leu His Val Thr Asn Thr 225 230 235 240 Ala Thr Thr Val Leu Leu Asp Glu Gln Gly Val Gly Pro Leu Cys Lys 245 250 255 Ala Asp Ser Leu Tyr Val Ser Ala Ala Asp Ile Cys Gly Leu Phe Thr 260 265 270 Asn Ser Ser Gly Thr Gln Gln Trp Arg Gly Leu Ala Arg Tyr Phe Lys 275 280 285 Ile Arg Leu Arg Lys Arg Ser Val Lys Asn Pro Tyr Pro Ile Ser Phe 290 295 300 Leu Leu Ser Asp Leu Ile Asn Arg Arg Thr Gln Arg Val Asp Gly Gln 305 310 315 320 Pro Met Tyr Gly Met Glu Ser Gln Val Glu Glu Val Arg Val Phe Asp 325 330 335 Gly Thr Glu Arg Leu Pro Gly Asp Pro Asp Met Ile Arg Tyr Ile Asp 340 345 350 Lys Gln Gly Gln Leu Gln Thr Lys Met Leu 355 360 75362PRTBK virus 75Met Ala Pro Thr Lys Arg Lys Gly Glu Cys Pro Gly Ala Ala Pro Lys 1 5 10 15 Lys Pro Lys Glu Pro Val Gln Val Pro Lys Leu Leu Ile Lys Gly Gly 20 25 30 Val Glu Val Leu Glu Val Lys Thr Gly Leu Asp Ala Ile Thr Glu Val 35 40 45 Glu Cys Phe Leu Asn Pro Glu Met Gly Asp Pro Asp Glu Asn Leu Arg 50 55 60 Gly Phe Ser Leu Lys Leu Ser Ala Lys Asn Asp Phe Ser Ser Asp Ser 65 70 75 80 Pro Asp Arg Lys Met Leu Pro Cys Tyr Ser Thr Ala Arg Ile Pro Leu 85 90 95 Pro Asn Leu Asn Glu Asp Leu Thr Cys Gly Asn Leu Leu Met Trp Glu 100 105 110 Ala Val Thr Val Gln Thr Glu Val Ile Gly Ile Thr Ser Met Leu Asn 115 120 125 Leu His Ala Gly Ser Gln Lys Val His Glu His Gly Gly Gly Lys Pro 130 135 140 Ile Gln Gly Ser Asn Phe His Phe Phe Ala Val Gly Gly Asp Pro Leu 145 150 155 160 Glu Met Gln Gly Val Leu Met Asn Tyr Arg Thr Lys Tyr Pro Glu Gly 165 170 175 Thr Ile Thr Pro Lys Asn Pro Thr Ala Gln Ser Gln Val Met Asn Thr 180 185 190 Asp His Lys Ala Tyr Leu Asp Lys Asn Asn Ala Tyr Pro Val Glu Cys 195 200 205 Trp Ile Pro Asp Pro Ser Arg Asn Glu Asn Thr Arg Tyr Phe Gly Thr 210 215 220 Phe Thr Gly Gly Glu Asn Val Pro Pro Val Leu His Val Thr Asn Thr 225 230 235 240 Ala Thr Thr Val Leu Leu Asp Glu Gln Gly Val Gly Pro Leu Cys Lys 245 250 255 Ala Asp Ser Leu Tyr Val Ser Ala Ala Asp Ile Cys Gly Leu Phe Thr 260 265 270 Asn Ser Ser Gly Thr Gln Gln Trp Arg Gly Leu Ala Arg Tyr Phe Lys 275 280 285 Ile Arg Leu Arg Lys Arg Ser Val Lys Asn Pro Tyr Pro Ile Ser Phe 290 295 300 Leu Leu Ser Asp Leu Ile Asn Arg Arg Thr Gln Arg Val Asp Gly Gln 305 310 315 320 Pro Met Tyr Gly Met Glu Ser Gln Val Glu Glu Val Arg Val Phe Asp 325 330 335 Gly Thr Glu Arg Leu Pro Gly Asp Pro Asp Met Ile Arg Tyr Ile Asp 340 345 350 Lys Gln Gly Gln Leu Gln Thr Lys Met Leu 355 360 76362PRTBK virus 76Met Ala Pro Thr Lys Arg Lys Gly Glu Cys Pro Gly Ala Ala Pro Lys 1 5 10 15

Lys Pro Lys Glu Pro Val Gln Val Pro Lys Leu Leu Ile Lys Gly Gly 20 25 30 Val Glu Val Leu Glu Val Lys Thr Gly Leu Asp Ala Ile Thr Glu Val 35 40 45 Glu Cys Phe Leu Asn Pro Glu Met Gly Asp Pro Asp Glu Asn Leu Arg 50 55 60 Gly Phe Ser Leu Lys Leu Ser Ala Gln Asn Asp Phe Asn Ser Asp Ser 65 70 75 80 Pro Glu Arg Lys Met Leu Pro Cys Tyr Ser Thr Ala Arg Ile Pro Leu 85 90 95 Pro Asn Leu Asn Glu Asp Leu Thr Cys Gly Asn Leu Leu Met Trp Glu 100 105 110 Ala Val Thr Val Gln Thr Glu Val Ile Gly Ile Thr Ser Met Leu Asn 115 120 125 Leu His Ala Gly Ser Gln Lys Val His Glu Asn Gly Gly Gly Lys Pro 130 135 140 Ile Gln Gly Ser Asn Phe His Phe Phe Ala Val Gly Gly Asp Pro Leu 145 150 155 160 Glu Met Gln Gly Val Leu Met Asn Tyr Arg Thr Lys Tyr Pro Glu Gly 165 170 175 Thr Ile Thr Pro Lys Asn Pro Thr Ala Gln Ser Gln Val Met Asn Thr 180 185 190 Asp His Lys Ala Tyr Leu Asp Lys Asn Asn Ala Tyr Pro Val Glu Cys 195 200 205 Trp Ile Pro Asp Pro Ser Arg Asn Glu Asn Thr Arg Tyr Phe Gly Thr 210 215 220 Phe Thr Gly Gly Glu Asn Val Pro Pro Val Leu His Val Thr Asn Thr 225 230 235 240 Ala Thr Thr Val Leu Leu Asp Glu Gln Gly Val Gly Pro Leu Cys Lys 245 250 255 Ala Asp Ser Leu Tyr Val Ser Ala Ala Asp Ile Cys Gly Leu Phe Thr 260 265 270 Asn Ser Ser Gly Thr Gln Gln Trp Arg Gly Leu Ala Arg Tyr Phe Lys 275 280 285 Ile Arg Leu Arg Lys Arg Ser Val Lys Asn Pro Tyr Pro Ile Ser Phe 290 295 300 Leu Leu Ser Asp Leu Ile Asn Arg Arg Thr Gln Arg Val Asp Gly Gln 305 310 315 320 Pro Met Tyr Gly Met Glu Ser Gln Val Glu Glu Val Arg Val Phe Asp 325 330 335 Gly Thr Glu Lys Leu Pro Gly Asp Pro Asp Met Ile Arg Tyr Ile Asp 340 345 350 Lys Gln Gly Gln Leu Gln Thr Lys Met Leu 355 360 77362PRTBK virus 77Met Ala Pro Thr Lys Arg Lys Gly Glu Cys Pro Gly Ala Ala Pro Lys 1 5 10 15 Lys Pro Lys Glu Pro Val Gln Val Pro Lys Leu Leu Ile Lys Gly Gly 20 25 30 Val Glu Val Leu Glu Val Lys Thr Gly Leu Asp Ala Ile Thr Glu Val 35 40 45 Glu Cys Phe Leu Asn Pro Glu Met Gly Asp Pro Asp Glu Asn Leu Arg 50 55 60 Gly Phe Ser Leu Lys Leu Ser Ala Glu Asn Asp Phe Ser Ser Asp Ser 65 70 75 80 Pro Glu Arg Lys Met Leu Pro Cys Tyr Ser Thr Ala Arg Ile Pro Leu 85 90 95 Pro Asn Leu Asn Glu Asp Leu Thr Cys Gly Asn Leu Leu Met Trp Glu 100 105 110 Ala Val Thr Val Gln Thr Glu Val Ile Gly Ile Thr Ser Met Leu Asn 115 120 125 Leu His Ala Gly Ser Gln Lys Val His Glu His Gly Gly Gly Lys Pro 130 135 140 Ile Gln Gly Ser Asn Phe His Phe Phe Ala Val Gly Gly Asp Pro Leu 145 150 155 160 Glu Met Gln Gly Val Leu Met Asn Tyr Arg Thr Lys Tyr Pro Glu Gly 165 170 175 Thr Ile Thr Pro Lys Asn Pro Thr Ala Gln Ser Gln Val Met Asn Thr 180 185 190 Asp His Lys Ala Tyr Leu Asp Lys Asn Asn Ala Tyr Pro Val Glu Cys 195 200 205 Trp Ile Pro Asp Pro Ser Arg Asn Glu Asn Thr Arg Tyr Phe Gly Thr 210 215 220 Phe Thr Gly Gly Glu Asn Val Pro Pro Val Leu His Val Thr Asn Thr 225 230 235 240 Ala Thr Thr Val Leu Leu Asp Glu Gln Gly Val Gly Pro Leu Cys Lys 245 250 255 Ala Asp Ser Leu Tyr Val Ser Ala Ala Asp Ile Cys Gly Leu Phe Thr 260 265 270 Asn Ser Ser Gly Thr Gln Gln Trp Arg Gly Leu Ala Arg Tyr Phe Lys 275 280 285 Ile Arg Leu Arg Lys Arg Ser Val Lys Asn Pro Tyr Pro Ile Ser Phe 290 295 300 Leu Leu Ser Asp Leu Ile Asn Arg Arg Thr Gln Arg Val Asp Gly Gln 305 310 315 320 Pro Met Tyr Gly Met Glu Ser Gln Val Glu Glu Val Arg Val Phe Asp 325 330 335 Gly Thr Glu Lys Leu Pro Gly Asp Pro Asp Met Ile Arg Tyr Ile Asp 340 345 350 Lys Gln Gly Gln Leu Gln Thr Lys Met Leu 355 360 78362PRTBK virus 78Met Ala Pro Thr Lys Arg Lys Gly Glu Cys Pro Gly Ala Ala Pro Lys 1 5 10 15 Lys Pro Lys Glu Pro Val Gln Val Pro Lys Leu Leu Ile Lys Gly Gly 20 25 30 Val Glu Val Leu Glu Val Lys Thr Gly Leu Asp Ala Ile Thr Glu Val 35 40 45 Glu Cys Phe Leu Asn Pro Glu Met Gly Asp Pro Asp Glu Asn Leu Arg 50 55 60 Gly Phe Ser Leu Lys Leu Ser Ala Glu Asn Asp Phe Ser Ser Asp Ser 65 70 75 80 Pro Glu Arg Lys Met Leu Pro Cys Tyr Ser Thr Ala Arg Ile Pro Leu 85 90 95 Pro Asn Leu Asn Glu Asp Leu Thr Cys Gly Asn Leu Leu Met Trp Glu 100 105 110 Ala Val Thr Val Gln Thr Glu Val Ile Gly Ile Thr Ser Met Leu Asn 115 120 125 Leu His Ala Gly Ser Gln Lys Val His Glu His Gly Gly Gly Lys Pro 130 135 140 Ile Gln Gly Ser Asn Phe His Phe Phe Ala Val Gly Gly Asp Pro Leu 145 150 155 160 Glu Met Gln Gly Val Leu Met Asn Tyr Arg Thr Lys Tyr Pro Glu Gly 165 170 175 Thr Ile Thr Pro Lys Asn Pro Thr Ala Gln Ser Gln Val Met Asn Thr 180 185 190 Asp His Lys Ala Tyr Leu Asp Lys Asn Asn Ala Tyr Pro Val Glu Cys 195 200 205 Trp Ile Pro Asp Pro Ser Arg Asn Glu Asn Thr Arg Tyr Phe Gly Thr 210 215 220 Phe Thr Gly Gly Glu Asn Val Pro Pro Val Leu His Val Thr Asn Thr 225 230 235 240 Ala Thr Thr Val Leu Leu Asp Glu Gln Gly Val Gly Pro Leu Cys Lys 245 250 255 Ala Asp Ser Leu Tyr Val Ser Ala Ala Asp Ile Cys Gly Leu Phe Thr 260 265 270 Asn Ser Ser Gly Thr Gln Gln Trp Arg Gly Leu Ala Arg Tyr Phe Lys 275 280 285 Ile Arg Leu Arg Lys Arg Ser Val Lys Asn Pro Tyr Pro Ile Ser Phe 290 295 300 Leu Leu Ser Asp Leu Ile Asn Arg Arg Thr Gln Arg Val Asp Gly Gln 305 310 315 320 Pro Met Tyr Gly Met Glu Ser Gln Val Glu Glu Val Arg Val Phe Asp 325 330 335 Gly Thr Glu Arg Leu Pro Gly Asp Pro Asp Met Ile Arg Tyr Ile Asp 340 345 350 Lys Gln Gly Gln Leu Gln Thr Lys Met Leu 355 360 79362PRTBK virus 79Met Ala Pro Thr Lys Arg Lys Gly Glu Cys Pro Gly Ala Ala Pro Lys 1 5 10 15 Lys Pro Lys Glu Pro Val Gln Val Pro Lys Leu Leu Ile Lys Gly Gly 20 25 30 Val Glu Val Leu Glu Val Lys Thr Gly Leu Asp Ala Ile Thr Glu Val 35 40 45 Glu Cys Phe Leu Asn Pro Glu Met Gly Asp Pro Asn Glu Asn Leu Arg 50 55 60 Gly Phe Ser Leu Lys Leu Ser Ala Glu Asn Asp Phe Ser Ser Asp Ser 65 70 75 80 Pro Glu Arg Lys Met Leu Pro Cys Tyr Ser Thr Ala Arg Ile Pro Leu 85 90 95 Pro Asn Leu Asn Glu Asp Leu Thr Cys Gly Asn Leu Leu Met Trp Glu 100 105 110 Ala Val Thr Val Gln Thr Glu Val Ile Gly Ile Thr Ser Met Leu Asn 115 120 125 Leu His Ala Gly Ser Gln Lys Val His Glu His Gly Gly Gly Lys Pro 130 135 140 Ile Gln Gly Ser Asn Phe His Phe Phe Ala Val Gly Gly Asp Pro Leu 145 150 155 160 Glu Met Gln Gly Val Leu Met Asn Tyr Arg Thr Lys Tyr Pro Glu Gly 165 170 175 Thr Ile Thr Pro Lys Asn Pro Thr Ala Gln Ser Gln Val Met Asn Thr 180 185 190 Asp His Lys Ala Tyr Leu Asp Lys Asn Asn Ala Tyr Pro Val Glu Cys 195 200 205 Trp Ile Pro Asp Pro Ser Arg Asn Glu Asn Thr Arg Tyr Phe Gly Thr 210 215 220 Phe Thr Gly Gly Glu Asn Val Pro Pro Val Leu His Val Thr Asn Thr 225 230 235 240 Ala Thr Thr Val Leu Leu Asp Glu Gln Gly Val Gly Pro Leu Cys Lys 245 250 255 Ala Asp Ser Leu Tyr Val Ser Ala Ala Asp Ile Cys Gly Leu Phe Thr 260 265 270 Asn Ser Ser Gly Thr Gln Gln Trp Arg Gly Leu Ala Arg Tyr Phe Lys 275 280 285 Ile Arg Leu Arg Lys Arg Ser Val Lys Asn Pro Tyr Pro Ile Ser Phe 290 295 300 Leu Leu Ser Asp Leu Ile Asn Arg Arg Thr Gln Arg Val Asp Gly Gln 305 310 315 320 Pro Met Tyr Gly Met Glu Ser Gln Val Glu Glu Val Arg Val Phe Asp 325 330 335 Gly Thr Glu Lys Leu Pro Gly Asp Pro Asp Met Ile Arg Tyr Ile Asp 340 345 350 Lys Gln Gly Gln Leu Gln Thr Lys Met Leu 355 360 80362PRTBK virus 80Met Ala Pro Thr Lys Arg Lys Gly Glu Cys Pro Gly Ala Ala Pro Lys 1 5 10 15 Lys Pro Lys Glu Pro Val Gln Val Pro Lys Leu Leu Ile Lys Gly Gly 20 25 30 Val Glu Val Leu Glu Val Lys Thr Gly Leu Asp Ala Ile Thr Glu Val 35 40 45 Glu Cys Phe Leu Asn Pro Glu Met Gly Asp Pro Asp Glu Asn Leu Arg 50 55 60 Gly Phe Ser Leu Lys Leu Ser Ala Glu Asn Asp Phe Ser Ser Asp Ser 65 70 75 80 Pro Glu Arg Lys Met Leu Pro Cys Tyr Ser Thr Ala Arg Ile Pro Leu 85 90 95 Pro Asn Leu Asn Glu Asp Leu Thr Cys Gly Asn Leu Leu Met Trp Glu 100 105 110 Ala Val Thr Val Gln Thr Glu Val Ile Gly Ile Thr Ser Met Leu Asn 115 120 125 Leu His Ala Gly Ser Gln Lys Val His Glu His Gly Gly Gly Lys Pro 130 135 140 Ile Gln Gly Ser Asn Phe His Phe Phe Ala Val Gly Gly Asp Pro Leu 145 150 155 160 Glu Met Gln Gly Val Leu Met Asn Tyr Arg Thr Lys Tyr Pro Glu Gly 165 170 175 Thr Ile Thr Pro Lys Asn Pro Thr Ala Gln Ser Gln Val Met Asn Thr 180 185 190 Asp His Met Ala Tyr Leu Asp Lys Asn Asn Ala Tyr Pro Val Glu Cys 195 200 205 Trp Ile Pro Asp Pro Ser Arg Asn Glu Asn Thr Arg Tyr Phe Gly Thr 210 215 220 Phe Thr Gly Gly Glu Asn Val Pro Pro Val Leu His Val Thr Asn Thr 225 230 235 240 Ala Thr Thr Val Leu Leu Asp Glu Gln Gly Val Gly Pro Leu Cys Lys 245 250 255 Ala Asp Ser Leu Tyr Val Ser Ala Ala Asp Ile Cys Gly Leu Phe Thr 260 265 270 Asn Ser Ser Gly Thr Gln Gln Trp Arg Gly Leu Ala Arg Tyr Phe Lys 275 280 285 Ile Arg Leu Arg Lys Arg Ser Val Lys Asn Pro Tyr Pro Ile Ser Phe 290 295 300 Leu Leu Ser Asp Leu Ile Asn Arg Arg Thr Gln Arg Val Asp Gly Gln 305 310 315 320 Pro Met Tyr Gly Met Glu Ser Gln Val Glu Glu Val Arg Val Phe Asp 325 330 335 Gly Thr Glu Lys Leu Pro Gly Asp Pro Asp Met Ile Arg Tyr Ile Asp 340 345 350 Lys Gln Gly Gln Leu Gln Thr Lys Met Leu 355 360 81362PRTBK virus 81Met Ala Pro Thr Lys Arg Lys Gly Glu Cys Pro Gly Ala Ala Pro Lys 1 5 10 15 Lys Pro Lys Glu Pro Val Gln Val Pro Lys Leu Leu Ile Lys Gly Gly 20 25 30 Val Glu Val Leu Glu Val Lys Thr Gly Leu Asp Ala Ile Thr Glu Val 35 40 45 Glu Cys Phe Leu Asn Pro Glu Met Gly Asp Pro Asp Glu Asn Leu Arg 50 55 60 Gly Phe Ser Leu Lys Leu Ser Ala Glu Asn Asp Phe Ser Ser Asp Ser 65 70 75 80 Pro Glu Arg Lys Met Leu Pro Cys Tyr Ser Thr Ala Arg Ile Pro Leu 85 90 95 Pro Asn Leu Asn Glu Asp Leu Thr Cys Gly Asn Leu Leu Met Trp Glu 100 105 110 Ala Val Thr Val Gln Thr Glu Val Ile Gly Ile Thr Ser Met Leu Asn 115 120 125 Leu His Ala Gly Ser Gln Lys Val His Glu His Gly Gly Gly Lys Pro 130 135 140 Ile Gln Gly Ser Asn Phe His Phe Phe Ala Val Gly Gly Asp Pro Leu 145 150 155 160 Glu Met Gln Gly Val Leu Met Asn Tyr Arg Thr Lys Tyr Pro Glu Gly 165 170 175 Thr Ile Thr Pro Lys Asn Pro Thr Ala Gln Ser Gln Val Met Asn Thr 180 185 190 Asp His Lys Ala Tyr Leu Asp Lys Asn Asn Ala Tyr Pro Val Glu Cys 195 200 205 Trp Ile Pro Asp Pro Thr Arg Asn Glu Asn Thr Arg Tyr Phe Gly Thr 210 215 220 Phe Thr Gly Gly Glu Asn Val Pro Pro Val Leu His Ile Thr Asn Thr 225 230 235 240 Ala Thr Thr Val Leu Leu Asp Glu Gln Gly Val Gly Pro Leu Cys Lys 245 250 255 Ala Asp Ser Leu Tyr Val Ser Ala Ala Asp Ile Cys Gly Leu Phe Thr 260 265 270 Asn Ser Ser Gly Thr Gln Gln Trp Arg Gly Leu Ala Arg Tyr Phe Lys 275 280 285 Ile Arg Leu Arg Lys Arg Ser Val Lys Asn Pro Tyr Pro Ile Ser Phe 290 295 300 Leu Leu Ser Asp Leu Ile Asn Arg Arg Thr Gln Arg Val Asp Gly Gln 305 310 315 320 Pro Met Tyr Gly Met Glu Ser Gln Val Glu Glu Val Arg Val Phe Asp 325 330 335 Gly Thr Glu Lys Leu Pro Gly Asp Pro Asp Met Ile Arg Tyr Ile Asp 340 345 350 Lys Gln Gly Gln Leu Gln Thr Lys Met Leu 355 360 82362PRTBK virus 82Met Ala Pro Thr Lys Arg Lys Gly Glu Cys Pro Gly Ala Ala Pro Lys 1 5 10 15 Lys Pro Lys Glu Pro Val Gln Val Pro Lys Leu Leu Ile Lys Gly Gly 20 25 30 Val Glu Val Leu Glu Val Lys Thr Gly Leu Asp Ala Ile Thr Glu Val 35 40 45 Glu Cys Phe Leu Asn Pro Glu Met Gly Asp Pro Asp Glu Asn Leu Arg 50 55 60 Gly Phe Ser Leu Lys Leu Ser Ala Glu Asn Asp Phe Ser Ser Asp Ser 65 70 75 80 Pro Glu Arg Lys Met Leu Pro Cys Tyr Ser Thr Ala Arg Ile Pro Leu 85 90 95 Pro Asn Leu Asn Glu Asp Leu Thr Cys Gly Asn Leu Leu Met Trp Glu 100 105 110 Ala Val Thr Val Gln Thr Glu Val Ile Gly Ile Thr Ser Met Leu Asn 115 120 125 Leu His Ala Gly Ser Gln Lys Val His Glu His Gly Gly Gly

Lys Pro 130 135 140 Ile Gln Gly Ser Asn Phe His Phe Phe Ala Val Gly Gly Asp Pro Leu 145 150 155 160 Glu Met Gln Gly Val Leu Met Asn Tyr Arg Thr Lys Tyr Pro Glu Gly 165 170 175 Thr Ile Thr Pro Lys Asn Pro Thr Ala Gln Ser Gln Val Met Asn Thr 180 185 190 Asp His Lys Ala Tyr Leu Asp Lys Asn Asn Ala Tyr Pro Val Glu Cys 195 200 205 Trp Ile Pro Asp Pro Ser Arg Asn Glu Asn Thr Arg Tyr Phe Gly Thr 210 215 220 Phe Thr Gly Gly Glu Asn Val Pro Pro Val Leu His Val Thr Asn Thr 225 230 235 240 Ala Thr Thr Val Leu Leu Asp Glu Gln Gly Val Gly Pro Leu Cys Lys 245 250 255 Ala Asp Ser Leu Tyr Val Ser Ala Ala Asp Ile Cys Gly Leu Phe Thr 260 265 270 Asn Ser Ser Gly Thr Gln Gln Trp Arg Gly Leu Ala Arg Tyr Phe Lys 275 280 285 Ile Arg Leu Arg Lys Arg Ser Val Lys Asn Pro Tyr Pro Ile Ser Phe 290 295 300 Leu Leu Ser Asp Leu Ile Asn Arg Arg Thr Gln Arg Val Asp Gly Gln 305 310 315 320 Pro Met Tyr Gly Met Glu Ser Gln Val Glu Glu Val Arg Val Phe Asp 325 330 335 Gly Thr Glu Lys Ser Ser Arg Asp Pro Asp Met Ile Arg Tyr Ile Asp 340 345 350 Lys Gln Gly Gln Leu Gln Thr Lys Met Leu 355 360 83362PRTBK virus 83Met Ala Pro Thr Lys Arg Lys Gly Glu Cys Pro Gly Ala Ala Pro Lys 1 5 10 15 Lys Pro Lys Glu Pro Val Gln Val Pro Lys Leu Leu Ile Lys Gly Gly 20 25 30 Val Glu Val Leu Glu Val Lys Thr Gly Leu Asp Ala Ile Thr Glu Val 35 40 45 Glu Cys Phe Leu Asn Pro Glu Met Gly Asp Pro Asp Glu Asn Leu Arg 50 55 60 Gly Phe Ser Leu Lys Leu Ser Ala Glu Asn Asp Phe Ser Ser Asp Ser 65 70 75 80 Pro Asp Arg Lys Met Leu Pro Cys Tyr Ser Thr Ala Arg Ile Pro Leu 85 90 95 Pro Asn Leu Asn Glu Asp Leu Thr Cys Gly Asn Leu Leu Met Trp Glu 100 105 110 Ala Val Thr Val Gln Thr Glu Val Ile Gly Ile Thr Ser Met Leu Asn 115 120 125 Leu His Ala Gly Ser Gln Lys Val His Glu His Gly Gly Gly Lys Pro 130 135 140 Ile Gln Gly Ser Asn Phe His Phe Phe Ala Val Gly Gly Asp Pro Leu 145 150 155 160 Glu Met Gln Gly Val Leu Met Asn Tyr Arg Thr Lys Tyr Pro Glu Gly 165 170 175 Thr Ile Thr Pro Lys Asn Pro Thr Ala Gln Ser Gln Val Met Asn Thr 180 185 190 Asp His Lys Ala Tyr Leu Asp Lys Asn Asn Ala Tyr Pro Val Glu Cys 195 200 205 Trp Ile Pro Asp Pro Ser Arg Asn Glu Asn Thr Arg Tyr Phe Gly Thr 210 215 220 Phe Thr Gly Gly Glu Asn Val Pro Pro Val Leu His Val Thr Asn Thr 225 230 235 240 Ala Thr Thr Val Leu Leu Asp Glu Gln Gly Val Gly Pro Leu Cys Lys 245 250 255 Ala Asp Ser Leu Tyr Val Ser Ala Ala Asp Ile Cys Gly Leu Phe Thr 260 265 270 Asn Ser Ser Gly Thr Gln Gln Trp Arg Gly Leu Ala Arg Tyr Phe Lys 275 280 285 Ile Arg Leu Arg Lys Arg Ser Val Lys Asn Pro Tyr Pro Ile Ser Phe 290 295 300 Leu Leu Ser Asp Leu Ile Asn Arg Arg Thr Gln Arg Val Asp Gly Gln 305 310 315 320 Pro Met Tyr Gly Met Glu Ser Gln Val Glu Glu Val Arg Val Phe Asp 325 330 335 Gly Thr Glu Arg Leu Pro Gly Asp Pro Asp Met Ile Arg Tyr Ile Asp 340 345 350 Lys Gln Gly Gln Leu Gln Thr Lys Met Val 355 360 84362PRTBK virus 84Met Ala Pro Thr Lys Arg Lys Gly Glu Cys Pro Gly Ala Ala Pro Lys 1 5 10 15 Lys Pro Lys Glu Pro Val Gln Val Pro Lys Leu Leu Ile Lys Gly Gly 20 25 30 Val Glu Val Leu Glu Val Lys Thr Gly Leu Asp Ala Ile Thr Glu Val 35 40 45 Glu Cys Phe Leu Asn Pro Glu Met Gly Asp Pro Asp Glu Asn Leu Arg 50 55 60 Gly Phe Ser Leu Lys Leu Ser Ala Glu Asn Asp Phe Ser Ser Asp Ser 65 70 75 80 Pro Glu Arg Lys Met Leu Pro Cys Tyr Ser Thr Ala Arg Ile Pro Leu 85 90 95 Pro Asn Leu Asn Glu Asp Leu Thr Cys Gly Asn Leu Leu Met Trp Glu 100 105 110 Ala Val Thr Val Gln Thr Glu Val Ile Gly Ile Thr Ser Met Leu Asn 115 120 125 Leu His Ala Gly Ser Gln Lys Val His Glu His Gly Gly Gly Lys Pro 130 135 140 Ile Gln Gly Ser Asn Phe His Phe Phe Ala Val Gly Gly Asp Pro Leu 145 150 155 160 Glu Met Gln Gly Val Leu Met Asn Tyr Arg Thr Lys Tyr Pro Glu Gly 165 170 175 Thr Ile Thr Pro Lys Asn Pro Thr Ala Gln Ser Gln Val Met Asn Thr 180 185 190 Asp His Lys Ala Tyr Leu Asp Lys Asn Asn Ala Tyr Pro Val Glu Cys 195 200 205 Trp Ile Pro Asp Pro Ser Arg Asn Glu Asn Thr Arg Tyr Phe Gly Thr 210 215 220 Phe Thr Gly Gly Glu Asn Val Pro Pro Val Leu His Val Thr Asn Thr 225 230 235 240 Ala Thr Thr Val Leu Leu Asp Glu Gln Gly Val Gly Pro Leu Cys Lys 245 250 255 Ala Asp Ser Leu Tyr Val Ser Ala Ala Asp Ile Cys Gly Leu Phe Thr 260 265 270 Asn Ser Ser Gly Thr Gln Gln Trp Arg Gly Leu Ala Arg Tyr Phe Lys 275 280 285 Ile Arg Leu Arg Lys Arg Ser Val Lys Asn Pro Tyr Pro Ile Ser Phe 290 295 300 Leu Leu Ser Asp Leu Ile Asn Arg Arg Thr Gln Arg Val Asp Gly Gln 305 310 315 320 Pro Met Tyr Gly Met Glu Ser Gln Val Glu Glu Val Arg Val Phe Asp 325 330 335 Gly Thr Glu Arg Leu Pro Gly Asp Pro Asp Met Ile Arg Tyr Ile Asp 340 345 350 Lys Gln Gly Gln Leu Gln Thr Lys Met Val 355 360 85362PRTBK virus 85Met Ala Pro Thr Lys Arg Lys Gly Glu Cys Pro Gly Ala Ala Pro Lys 1 5 10 15 Lys Pro Lys Glu Pro Val Gln Val Pro Lys Leu Leu Ile Lys Gly Gly 20 25 30 Val Glu Val Leu Glu Val Lys Thr Gly Leu Asp Ala Ile Thr Glu Val 35 40 45 Glu Cys Phe Leu Asn Pro Glu Met Gly Asp Pro Asp Glu Asn Leu Arg 50 55 60 Gly Phe Ser Leu Lys Leu Ser Ala Glu Asn Asp Phe Ser Ser Asp Ser 65 70 75 80 Pro Glu Arg Lys Met Leu Pro Cys Tyr Ser Thr Ala Arg Ile Pro Leu 85 90 95 Pro Asn Leu Asn Glu Asp Leu Thr Cys Gly Asn Leu Leu Met Trp Glu 100 105 110 Ala Val Thr Val Gln Thr Glu Val Ile Gly Ile Thr Ser Met Leu Asn 115 120 125 Leu His Ala Gly Ser Lys Lys Val His Glu His Gly Gly Gly Lys Pro 130 135 140 Ile Gln Gly Ser Asn Phe His Phe Phe Ala Val Gly Gly Asp Pro Leu 145 150 155 160 Glu Met Gln Gly Val Leu Met Asn Tyr Arg Thr Lys Tyr Pro Glu Gly 165 170 175 Thr Ile Thr Pro Lys Asn Pro Thr Ala Gln Ser Gln Val Met Asn Thr 180 185 190 Asp His Lys Ala Tyr Leu Asp Lys Asn Asn Ala Tyr Pro Val Glu Cys 195 200 205 Trp Ile Pro Asp Pro Ser Arg Asn Glu Asn Thr Arg Tyr Phe Gly Thr 210 215 220 Phe Thr Gly Gly Glu Asn Val Pro Pro Val Leu His Val Thr Asn Thr 225 230 235 240 Ala Thr Thr Val Leu Leu Asp Glu Gln Gly Val Gly Pro Leu Cys Lys 245 250 255 Ala Asp Ser Leu Tyr Val Ser Ala Ala Asp Ile Cys Gly Leu Phe Thr 260 265 270 Asn Ser Ser Gly Thr Gln Gln Trp Arg Gly Leu Ala Arg Tyr Phe Lys 275 280 285 Ile Arg Leu Arg Lys Arg Ser Val Lys Asn Pro Tyr Pro Ile Ser Phe 290 295 300 Leu Leu Ser Asp Leu Ile Asn Arg Arg Thr Gln Arg Val Asp Gly Gln 305 310 315 320 Pro Met Tyr Gly Met Glu Ser Gln Val Glu Glu Val Arg Val Phe Asp 325 330 335 Gly Thr Glu Arg Leu Pro Gly Asp Pro Asp Met Ile Arg Tyr Ile Asp 340 345 350 Lys Gln Gly Gln Leu Gln Thr Lys Met Val 355 360 86362PRTBK virus 86Met Ala Pro Thr Lys Arg Lys Gly Glu Cys Pro Gly Ala Ala Pro Lys 1 5 10 15 Lys Pro Lys Glu Pro Met Gln Val Pro Lys Leu Leu Ile Lys Gly Gly 20 25 30 Val Glu Val Leu Glu Val Lys Thr Gly Leu Asp Ala Ile Thr Glu Val 35 40 45 Glu Cys Phe Leu Asn Pro Glu Met Gly Asp Pro Asp Glu Asn Leu Arg 50 55 60 Gly Phe Ser Leu Lys Leu Ser Ala Glu Asn Asp Phe Ser Ser Asp Ser 65 70 75 80 Pro Glu Arg Lys Met Leu Pro Cys Tyr Ser Thr Ala Arg Ile Pro Leu 85 90 95 Pro Asn Leu Asn Glu Asp Leu Thr Cys Gly Asn Leu Leu Met Trp Glu 100 105 110 Ala Val Thr Val Gln Thr Glu Val Ile Gly Ile Thr Ser Met Leu Asn 115 120 125 Leu His Ala Gly Ser Gln Lys Val His Glu His Gly Gly Gly Lys Pro 130 135 140 Ile Gln Gly Ser Asn Phe His Phe Phe Ala Val Gly Gly Asp Pro Leu 145 150 155 160 Glu Met Gln Gly Val Leu Met Asn Tyr Arg Thr Lys Tyr Pro Glu Gly 165 170 175 Thr Ile Thr Pro Lys Asn Pro Thr Ala Gln Ser Gln Val Met Asn Thr 180 185 190 Asp His Lys Ala Tyr Leu Asp Lys Asn Asn Ala Tyr Pro Val Glu Cys 195 200 205 Trp Ile Pro Asp Pro Ser Arg Asn Glu Asn Thr Arg Tyr Phe Gly Thr 210 215 220 Phe Thr Gly Gly Glu Asn Val Pro Pro Val Leu His Val Thr Asn Thr 225 230 235 240 Ala Thr Thr Val Leu Leu Asp Glu Gln Gly Val Gly Pro Leu Cys Lys 245 250 255 Ala Asp Ser Leu Tyr Val Ser Ala Ala Asp Ile Cys Gly Leu Phe Thr 260 265 270 Asn Ser Ser Gly Thr Gln Gln Trp Arg Gly Leu Ala Arg Tyr Phe Lys 275 280 285 Ile Arg Leu Arg Lys Arg Ser Val Lys Asn Pro Tyr Pro Ile Ser Phe 290 295 300 Leu Leu Ser Asp Leu Ile Asn Arg Arg Thr Gln Arg Val Asp Gly Gln 305 310 315 320 Pro Met Tyr Gly Met Glu Ser Gln Val Glu Glu Val Arg Val Phe Asp 325 330 335 Gly Thr Glu Arg Leu Pro Gly Asp Pro Asp Met Ile Arg Tyr Ile Asp 340 345 350 Lys Gln Gly Gln Leu Gln Thr Lys Met Val 355 360 87362PRTBK virus 87Met Ala Pro Thr Lys Arg Lys Gly Glu Cys Pro Gly Ala Ala Pro Lys 1 5 10 15 Lys Pro Lys Glu Pro Val Gln Val Pro Lys Leu Leu Ile Lys Gly Gly 20 25 30 Val Glu Val Leu Glu Val Lys Thr Gly Leu Asp Ala Ile Thr Glu Val 35 40 45 Glu Cys Phe Leu Asn Pro Glu Met Gly Asp Pro Asp Glu Asn Leu Arg 50 55 60 Gly Phe Ser Leu Lys Leu Ser Ala Glu Asn Asp Phe Ser Ser Asp Ser 65 70 75 80 Pro Glu Arg Lys Met Leu Pro Cys Tyr Ser Thr Ala Arg Ile Pro Leu 85 90 95 Pro Asn Leu Asn Glu Asp Leu Thr Cys Gly Asn Leu Leu Met Trp Glu 100 105 110 Ala Val Thr Val Gln Thr Glu Val Ile Gly Ile Thr Ser Met Leu Asn 115 120 125 Leu His Ala Gly Ser Gln Lys Val His Glu His Gly Gly Gly Lys Pro 130 135 140 Ile Gln Gly Ser Asn Phe His Phe Phe Ala Val Gly Gly Asp Pro Leu 145 150 155 160 Glu Met Gln Gly Val Leu Met Asn Tyr Arg Thr Lys Tyr Pro Glu Gly 165 170 175 Thr Ile Thr Pro Lys Asn Pro Thr Ala Gln Ser Gln Val Met Asn Thr 180 185 190 Asp His Lys Ala Tyr Leu Asp Lys Asn Asn Ala Tyr Pro Val Glu Cys 195 200 205 Trp Ile Pro Asp Pro Ser Arg Asn Glu Asn Thr Arg Tyr Phe Gly Thr 210 215 220 Phe Thr Gly Gly Glu Asn Val Pro Pro Val Leu His Val Thr Asn Thr 225 230 235 240 Ala Thr Thr Val Leu Leu Asp Glu Gln Gly Val Gly Pro Leu Cys Lys 245 250 255 Ala Asn Ser Leu Tyr Val Ser Ala Ala Asp Ile Cys Gly Leu Phe Thr 260 265 270 Asn Ser Ser Gly Thr Gln Gln Trp Arg Gly Leu Ala Arg Tyr Phe Lys 275 280 285 Ile Arg Leu Arg Lys Arg Ser Val Lys Asn Pro Tyr Pro Ile Ser Phe 290 295 300 Leu Leu Ser Asp Leu Ile Asn Arg Arg Thr Gln Arg Val Asp Gly Gln 305 310 315 320 Pro Met Tyr Gly Met Glu Ser Gln Val Glu Glu Val Arg Val Phe Asp 325 330 335 Gly Thr Glu Arg Leu Pro Gly Asp Pro Asp Met Ile Arg Tyr Ile Asp 340 345 350 Lys Gln Gly Gln Leu Gln Thr Lys Met Val 355 360 88362PRTBK virus 88Met Ala Pro Thr Lys Arg Lys Gly Glu Cys Pro Gly Ala Ala Pro Lys 1 5 10 15 Lys Pro Lys Glu Pro Val Gln Val Pro Lys Leu Leu Ile Lys Gly Gly 20 25 30 Val Glu Val Leu Glu Val Lys Thr Gly Leu Asp Ala Ile Thr Glu Val 35 40 45 Glu Cys Phe Leu Asn Pro Glu Met Gly Asp Pro Asp Glu Asn Leu Arg 50 55 60 Gly Phe Ser Leu Lys Leu Ser Ala Glu Asn Asp Phe Ser Ser Asp Ser 65 70 75 80 Pro Glu Arg Lys Met Leu Pro Cys Tyr Ser Thr Ala Arg Ile Pro Leu 85 90 95 Pro Asn Leu Asn Glu Asp Leu Thr Cys Gly Asn Leu Leu Met Trp Glu 100 105 110 Ala Val Thr Val Gln Thr Glu Val Ile Gly Ile Thr Ser Met Leu Asn 115 120 125 Leu His Ala Gly Ser Gln Lys Val His Glu His Gly Gly Gly Lys Pro 130 135 140 Ile Gln Gly Ser Asn Phe His Phe Phe Ala Val Gly Gly Asp Pro Leu 145 150 155 160 Glu Met Gln Gly Val Leu Met Asn Tyr Arg Thr Lys Tyr Pro Glu Gly 165 170 175 Thr Ile Thr Pro Lys Asn Pro Thr Ala Gln Ser Gln Val Met Asn Thr 180 185 190 Asp His Lys Ala Tyr Leu Asp Lys Asn Asn Ala Tyr Pro Val Glu Cys 195 200 205 Trp Ile Pro Asp Pro Ser Arg Asn Glu Asn Thr Arg Tyr Phe Gly Thr 210 215 220 Phe Thr Gly Gly Glu Asn Val Pro Pro Val Leu His Val Thr Asn Thr 225 230 235 240 Ala Thr Thr Val Leu Leu Asp Glu Gln Gly Val Gly Pro Leu Cys Lys 245 250

255 Ala Asp Ser Leu Tyr Val Ser Ala Ala Asp Ile Cys Gly Leu Phe Thr 260 265 270 Asn Ser Ser Gly Thr Gln Gln Trp Arg Gly Leu Ala Arg Tyr Phe Lys 275 280 285 Ile Arg Leu Arg Lys Arg Ser Val Lys Asn Pro Tyr Pro Ile Ser Phe 290 295 300 Leu Leu Ser Asp Leu Ile Asn Arg Gly Thr Gln Arg Val Asp Gly Gln 305 310 315 320 Pro Met Tyr Gly Met Glu Ser Gln Val Glu Glu Val Arg Val Phe Asp 325 330 335 Gly Thr Glu Arg Leu Pro Gly Asp Pro Asp Met Ile Arg Tyr Ile Asp 340 345 350 Lys Gln Gly Gln Leu Gln Thr Lys Met Val 355 360 89362PRTBK virus 89Met Ala Pro Thr Lys Arg Lys Gly Glu Cys Pro Gly Ala Ala Pro Lys 1 5 10 15 Lys Pro Lys Glu Pro Val Gln Val Pro Lys Leu Leu Ile Lys Gly Gly 20 25 30 Val Glu Val Leu Glu Val Lys Thr Gly Leu Asp Ala Ile Thr Glu Val 35 40 45 Glu Cys Phe Leu Asn Pro Glu Met Gly Asp Pro Asp Glu Asn Leu Arg 50 55 60 Gly Phe Ser Leu Lys Leu Ser Ala Glu Asn Asp Phe Ser Ser Asp Ser 65 70 75 80 Pro Asp Arg Lys Met Leu Pro Cys Tyr Ser Thr Ala Arg Ile Pro Leu 85 90 95 Pro Asn Leu Asn Glu Asp Leu Thr Cys Gly Asn Leu Leu Met Trp Glu 100 105 110 Ala Val Thr Val Gln Thr Glu Val Ile Gly Ile Thr Ser Met Leu Asn 115 120 125 Leu His Ala Gly Ser Gln Lys Val His Glu His Gly Gly Gly Lys Pro 130 135 140 Ile Gln Gly Ser Asn Phe His Phe Phe Ala Val Gly Gly Asp Pro Leu 145 150 155 160 Glu Met Gln Gly Val Leu Met Asn Tyr Arg Thr Lys Tyr Pro Glu Gly 165 170 175 Thr Ile Thr Pro Lys Asn Pro Thr Ala Gln Ser Gln Val Met Asn Thr 180 185 190 Asp His Lys Ala Tyr Leu Asp Lys Asn Asn Ala Tyr Pro Val Glu Cys 195 200 205 Trp Ile Pro Asp Pro Ser Arg Asn Glu Asn Thr Arg Tyr Phe Gly Thr 210 215 220 Phe Thr Gly Gly Glu Asn Val Pro Pro Val Leu His Val Thr Asn Thr 225 230 235 240 Ala Thr Thr Val Leu Leu Asp Glu Gln Gly Val Gly Pro Leu Cys Lys 245 250 255 Ala Asp Ser Leu Tyr Val Ser Ala Ala Asp Ile Cys Gly Leu Phe Thr 260 265 270 Asn Ser Ser Gly Thr Gln Gln Trp Arg Gly Leu Ala Arg Tyr Phe Lys 275 280 285 Ile Arg Leu Arg Lys Arg Ser Val Lys Asn Pro Tyr Pro Ile Ser Phe 290 295 300 Leu Leu Ser Asp Leu Ile Asn Arg Arg Thr Gln Arg Val Asp Gly Gln 305 310 315 320 Pro Met Tyr Gly Met Glu Ser Gln Val Glu Glu Val Arg Val Phe Asp 325 330 335 Gly Thr Glu Lys Leu Pro Gly Asp Pro Asp Met Ile Arg Tyr Ile Asp 340 345 350 Lys Gln Gly Gln Leu Gln Thr Lys Met Leu 355 360 90362PRTBK virus 90Met Ala Pro Thr Lys Arg Lys Gly Glu Cys Pro Gly Ala Ala Pro Lys 1 5 10 15 Lys Pro Lys Glu Pro Val Gln Val Pro Lys Leu Leu Ile Lys Gly Gly 20 25 30 Val Glu Val Leu Glu Val Lys Thr Gly Leu Asp Ala Ile Thr Glu Val 35 40 45 Glu Cys Phe Leu Asn Pro Glu Met Gly Asp Pro Asp Glu Asn Leu Arg 50 55 60 Gly Phe Ser Leu Lys Leu Ser Ala Glu Asn Asp Phe Ser Ser Asp Ser 65 70 75 80 Pro Asp Arg Lys Met Leu Pro Cys Tyr Ser Thr Ala Arg Ile Pro Leu 85 90 95 Pro Asn Leu Asn Glu Asp Leu Thr Cys Gly Asn Leu Leu Met Trp Glu 100 105 110 Ala Val Thr Val Gln Thr Glu Val Ile Gly Ile Thr Ser Met Leu Asn 115 120 125 Leu His Ala Gly Ser Gln Lys Val His Glu His Gly Gly Gly Lys Pro 130 135 140 Ile Gln Gly Ser Asn Phe His Phe Phe Ala Val Gly Gly Asp Pro Leu 145 150 155 160 Glu Met Gln Gly Val Leu Met Asn Tyr Arg Thr Lys Tyr Pro Glu Gly 165 170 175 Thr Ile Thr Pro Lys Asn Pro Thr Ala Gln Ser Gln Val Met Asn Thr 180 185 190 Asp His Lys Ala Tyr Leu Asp Lys Asn Asn Ala Tyr Pro Val Glu Cys 195 200 205 Trp Ile Pro Asp Pro Ser Arg Asn Glu Asn Thr Arg Tyr Phe Gly Thr 210 215 220 Phe Thr Gly Gly Glu Asn Val Pro Pro Val Leu His Val Thr Asn Thr 225 230 235 240 Ala Thr Thr Val Leu Leu Asp Glu Gln Gly Val Gly Pro Leu Cys Lys 245 250 255 Ala Asp Ser Leu Tyr Val Ser Ala Ala Asp Ile Cys Gly Leu Phe Thr 260 265 270 Asn Ser Ser Gly Thr Gln Gln Trp Arg Gly Leu Ala Arg Tyr Phe Lys 275 280 285 Ile Arg Leu Arg Lys Arg Ser Val Lys Asn Pro Tyr Pro Ile Ser Phe 290 295 300 Leu Leu Ser Asp Leu Ile Asn Arg Arg Thr Gln Arg Val Asp Gly Gln 305 310 315 320 Pro Met Tyr Gly Met Glu Ser Gln Val Glu Glu Val Arg Val Phe Asp 325 330 335 Gly Thr Glu Arg Leu Pro Gly Asp Pro Asp Met Ile Arg Tyr Ile Asp 340 345 350 Lys Gln Gly Gln Leu Gln Thr Lys Met Leu 355 360 91362PRTBK virus 91Met Ala Pro Thr Lys Arg Lys Gly Glu Cys Pro Gly Ala Ala Pro Lys 1 5 10 15 Lys Pro Lys Glu Pro Val Gln Val Pro Lys Leu Leu Ile Lys Gly Gly 20 25 30 Val Glu Val Leu Glu Val Lys Thr Gly Leu Asp Ala Ile Thr Glu Val 35 40 45 Glu Cys Phe Leu Asn Pro Glu Met Gly Asp Pro Asp Glu Asn Leu Arg 50 55 60 Gly Phe Ser Leu Arg Leu Ser Ala Glu Asn Asp Phe Ser Ser Asp Ser 65 70 75 80 Pro Glu Arg Lys Met Leu Pro Cys Tyr Ser Thr Ala Arg Ile Pro Leu 85 90 95 Pro Asn Leu Asn Glu Asp Leu Thr Cys Gly Asn Leu Leu Met Trp Glu 100 105 110 Ala Val Thr Val Gln Thr Glu Val Ile Gly Ile Thr Ser Met Leu Asn 115 120 125 Leu His Ala Gly Ser Gln Lys Val His Glu His Gly Gly Gly Lys Pro 130 135 140 Ile Gln Gly Ser Asn Phe His Phe Phe Ala Val Gly Gly Asp Pro Leu 145 150 155 160 Glu Met Gln Gly Val Leu Met Asn Tyr Arg Thr Lys Tyr Pro Glu Gly 165 170 175 Thr Ile Thr Pro Lys Asn Pro Thr Ala Gln Ser Gln Val Met Asn Thr 180 185 190 Asp His Lys Ala Tyr Leu Asp Lys Asn Asn Ala Tyr Pro Val Glu Cys 195 200 205 Trp Ile Pro Asp Pro Ser Arg Asn Glu Asn Thr Arg Tyr Phe Gly Thr 210 215 220 Phe Thr Gly Gly Glu Asn Val Pro Pro Val Leu His Val Thr Asn Thr 225 230 235 240 Ala Thr Thr Val Leu Leu Asp Glu Gln Gly Val Gly Pro Leu Cys Lys 245 250 255 Ala Asp Ser Leu Tyr Val Ser Ala Ala Asp Ile Cys Gly Leu Phe Thr 260 265 270 Asn Ser Ser Gly Thr Gln Gln Trp Arg Gly Leu Ala Arg Tyr Phe Lys 275 280 285 Ile Arg Leu Arg Lys Arg Ser Val Lys Asn Pro Tyr Pro Ile Ser Phe 290 295 300 Leu Leu Ser Asp Leu Ile Asn Arg Arg Thr Gln Arg Val Asp Gly Gln 305 310 315 320 Pro Met Tyr Gly Met Glu Ser Gln Val Glu Glu Val Arg Val Phe Asp 325 330 335 Gly Thr Glu Lys Leu Pro Gly Asp Pro Asp Met Ile Arg Tyr Ile Asp 340 345 350 Lys Gln Gly Gln Leu Gln Thr Lys Met Leu 355 360 92362PRTBK virus 92Met Ala Pro Thr Lys Arg Lys Gly Glu Cys Pro Gly Ala Ala Pro Lys 1 5 10 15 Lys Pro Lys Glu Pro Val Gln Val Pro Lys Leu Leu Ile Lys Gly Gly 20 25 30 Val Glu Val Leu Glu Val Lys Thr Gly Leu Asp Ala Ile Thr Glu Val 35 40 45 Glu Cys Phe Leu Asn Pro Glu Met Gly Asp Pro Asp Glu Asn Leu Arg 50 55 60 Gly Phe Ser Leu Lys Val Ser Ala Glu Asn Asp Phe Ser Ser Asp Ser 65 70 75 80 Pro Asp Arg Lys Met Leu Pro Cys Tyr Ser Thr Ala Arg Ile Pro Leu 85 90 95 Pro Asn Leu Asn Glu Asp Leu Thr Cys Gly Asn Leu Leu Met Trp Glu 100 105 110 Ala Val Thr Val Gln Thr Glu Val Ile Gly Ile Thr Ser Met Leu Asn 115 120 125 Leu His Ala Gly Ser Gln Lys Val His Glu His Gly Gly Gly Lys Pro 130 135 140 Ile Gln Gly Ser Asn Phe His Phe Phe Ala Val Gly Gly Asp Pro Leu 145 150 155 160 Glu Met Gln Gly Val Leu Met Asn Tyr Arg Thr Lys Tyr Pro Glu Gly 165 170 175 Thr Ile Thr Pro Lys Asn Pro Thr Ala Gln Ser Gln Val Met Asn Thr 180 185 190 Asp His Lys Ala Tyr Leu Asp Lys Asn Asn Ala Tyr Pro Val Glu Cys 195 200 205 Trp Ile Pro Asp Pro Ser Arg Asn Glu Asn Thr Arg Tyr Phe Gly Thr 210 215 220 Phe Thr Gly Gly Glu Asn Val Pro Pro Val Leu His Val Thr Asn Thr 225 230 235 240 Ala Thr Thr Val Leu Leu Asp Glu Gln Gly Val Gly Pro Leu Cys Lys 245 250 255 Ala Asp Ser Leu Tyr Val Ser Ala Ala Asp Ile Cys Gly Leu Phe Thr 260 265 270 Asn Ser Ser Gly Thr Gln Gln Trp Arg Gly Leu Ala Arg Tyr Phe Lys 275 280 285 Ile Arg Leu Arg Lys Arg Ser Val Lys Asn Pro Tyr Pro Ile Ser Phe 290 295 300 Leu Leu Ser Asp Leu Ile Asn Arg Arg Thr Gln Arg Val Asp Gly Gln 305 310 315 320 Pro Met Tyr Gly Met Glu Ser Gln Val Glu Glu Val Arg Val Phe Asp 325 330 335 Gly Thr Glu Arg Leu Pro Gly Asp Pro Asp Met Ile Arg Tyr Ile Asp 340 345 350 Lys Gln Gly Gln Leu Gln Thr Lys Met Leu 355 360 93362PRTBK virus 93Met Ala Pro Thr Lys Lys Lys Gly Glu Cys Pro Gly Ala Ala Pro Lys 1 5 10 15 Lys Pro Lys Glu Pro Val Gln Val Pro Lys Leu Leu Ile Lys Gly Gly 20 25 30 Val Glu Val Leu Glu Val Lys Thr Gly Leu Asp Ala Ile Thr Glu Val 35 40 45 Glu Cys Phe Leu Asn Pro Glu Met Gly Asp Pro Asp Glu Asn Leu Arg 50 55 60 Gly Phe Ser Leu Lys Leu Ser Ala Glu Asn Asp Phe Ser Ser Asp Ser 65 70 75 80 Pro Asp Arg Lys Met Leu Pro Cys Tyr Ser Thr Ala Arg Ile Pro Leu 85 90 95 Pro Asn Leu Asn Glu Asp Leu Thr Cys Gly Asn Leu Leu Met Trp Glu 100 105 110 Ala Val Thr Val Gln Thr Glu Val Ile Gly Ile Thr Ser Met Leu Asn 115 120 125 Leu His Ala Gly Ser Gln Lys Val His Glu His Gly Gly Gly Lys Pro 130 135 140 Ile Gln Gly Ser Asn Phe His Phe Phe Ala Val Gly Gly Asp Pro Leu 145 150 155 160 Glu Met Gln Gly Val Leu Met Asn Tyr Arg Thr Lys Tyr Pro Glu Gly 165 170 175 Thr Ile Thr Pro Lys Asn Pro Thr Ala Gln Ser Gln Val Met Asn Thr 180 185 190 Asp His Lys Ala Tyr Leu Asp Lys Asn Asn Ala Tyr Pro Val Glu Cys 195 200 205 Trp Ile Pro Asp Pro Ser Arg Asn Glu Asn Thr Arg Tyr Phe Gly Thr 210 215 220 Phe Thr Gly Gly Glu Asn Val Pro Pro Val Leu His Val Thr Asn Thr 225 230 235 240 Ala Thr Thr Val Leu Leu Asp Glu Gln Gly Val Gly Pro Leu Cys Lys 245 250 255 Ala Asp Ser Leu Tyr Val Ser Ala Ala Asp Ile Cys Gly Leu Phe Thr 260 265 270 Asn Ser Ser Gly Thr Gln Gln Trp Arg Gly Leu Ala Arg Tyr Phe Lys 275 280 285 Ile Arg Leu Arg Lys Arg Ser Val Lys Asn Pro Tyr Pro Ile Ser Phe 290 295 300 Leu Leu Ser Asp Leu Ile Asn Arg Arg Thr Gln Arg Val Asp Gly Gln 305 310 315 320 Pro Met Tyr Gly Met Glu Ser Gln Val Glu Glu Val Arg Val Phe Asp 325 330 335 Gly Thr Glu Arg Leu Pro Gly Asp Pro Asp Met Ile Arg Tyr Ile Asp 340 345 350 Lys Gln Gly Gln Leu Gln Thr Lys Met Leu 355 360 94362PRTBK virus 94Met Ala Pro Thr Lys Arg Lys Gly Glu Cys Pro Gly Ala Ala Pro Lys 1 5 10 15 Lys Pro Lys Glu Pro Val Gln Val Pro Lys Leu Leu Ile Lys Gly Gly 20 25 30 Val Glu Val Leu Glu Val Lys Thr Gly Val Asp Ala Ile Thr Glu Val 35 40 45 Glu Cys Phe Leu Asn Pro Glu Met Gly Asp Pro Asp Glu Asn Leu Arg 50 55 60 Gly Phe Ser Leu Lys Leu Ser Ala Glu Asn Asp Phe Ser Ser Asp Ser 65 70 75 80 Pro Asp Lys Lys Met Leu Pro Cys Tyr Ser Thr Ala Arg Ile Pro Leu 85 90 95 Pro Asn Leu Asn Glu Asp Leu Thr Cys Gly Asn Leu Leu Met Trp Glu 100 105 110 Ala Val Thr Val Gln Thr Glu Val Ile Gly Ile Thr Ser Met Leu Asn 115 120 125 Leu His Ala Gly Ser Gln Lys Val His Glu His Gly Gly Gly Lys Pro 130 135 140 Ile Gln Gly Ser Asn Phe His Phe Phe Ala Val Gly Gly Asp Pro Leu 145 150 155 160 Glu Met Gln Gly Val Leu Met Asn Tyr Arg Thr Lys Tyr Pro Glu Gly 165 170 175 Thr Ile Thr Pro Lys Asn Pro Thr Ala Gln Ser Gln Val Met Asn Thr 180 185 190 Asp His Lys Ala Tyr Leu Asp Lys Asn Asn Ala Tyr Pro Val Glu Cys 195 200 205 Trp Ile Pro Asp Pro Ser Arg Asn Glu Asn Thr Arg Tyr Phe Gly Thr 210 215 220 Leu Thr Gly Gly Glu Asn Val Pro Pro Val Leu His Val Thr Asn Thr 225 230 235 240 Ala Thr Thr Val Leu Leu Asp Glu Gln Gly Val Gly Pro Leu Cys Lys 245 250 255 Ala Asp Ser Leu Tyr Val Ser Ala Ala Asp Ile Cys Gly Leu Phe Thr 260 265 270 Asn Ser Ser Gly Thr Gln Gln Trp Arg Gly Leu Ala Arg Tyr Phe Lys 275 280 285 Ile Arg Leu Arg Lys Arg Ser Val Lys Asn Pro Tyr Pro Ile Ser Phe 290 295 300 Leu Leu Ser Asp Leu Ile Asn Arg Arg Thr Gln Arg Val Asp Gly Gln 305 310 315 320 Pro Met Tyr Gly Met Glu Ser Gln Val Glu Glu Val Arg Val Phe Asp 325 330 335 Gly Thr Glu Lys Leu Pro Gly Asp Pro Asp Met Ile Arg Tyr Ile Asp 340 345 350 Lys Gln Gly Gln Leu Gln Thr Lys Met Leu 355 360 95362PRTBK virus 95Met Ala Pro Thr Lys Arg Lys Gly Glu Cys Pro Gly Ala Ala Pro Lys 1

5 10 15 Lys Pro Lys Asp Pro Val Gln Val Pro Lys Leu Leu Ile Lys Gly Gly 20 25 30 Val Glu Val Leu Glu Val Lys Thr Gly Val Asp Ala Ile Thr Glu Val 35 40 45 Glu Cys Phe Leu Asn Pro Glu Met Gly Asp Pro Asp Lys Asn Leu Arg 50 55 60 Gly Phe Ser Leu Lys Leu Ser Ala Glu Asn Asp Phe Ser Ser Asp Ser 65 70 75 80 Pro Glu Arg Lys Met Leu Pro Cys Tyr Ser Thr Ala Arg Ile Pro Leu 85 90 95 Pro Asn Leu Asn Glu Asp Leu Thr Cys Gly Asn Leu Leu Met Trp Glu 100 105 110 Ala Val Thr Val Gln Thr Glu Val Ile Gly Ile Thr Ser Met Leu Asn 115 120 125 Leu His Ala Gly Ser Gln Lys Val His Glu His Gly Gly Gly Lys Pro 130 135 140 Ile Gln Gly Ser Asn Phe His Phe Phe Ala Val Gly Gly Asp Pro Leu 145 150 155 160 Glu Met Gln Gly Val Leu Met Asn Tyr Arg Thr Lys Tyr Pro Glu Gly 165 170 175 Thr Ile Thr Pro Lys Asn Pro Thr Ala Gln Ser Gln Val Met Asn Thr 180 185 190 Asp His Lys Ala Tyr Leu Asp Lys Asn Asn Ala Tyr Pro Val Glu Cys 195 200 205 Trp Ile Pro Asp Pro Ser Arg Asn Glu Asn Thr Arg Tyr Phe Gly Thr 210 215 220 Leu Thr Gly Gly Glu Asn Val Pro Pro Val Leu His Val Thr Asn Thr 225 230 235 240 Ala Thr Thr Val Leu Leu Asp Glu Gln Gly Val Gly Pro Leu Cys Lys 245 250 255 Ala Asp Ser Leu Tyr Val Ser Ala Ala Asp Ile Cys Gly Leu Phe Thr 260 265 270 Asn Ser Ser Gly Thr Gln Gln Trp Arg Gly Leu Ala Arg Tyr Phe Lys 275 280 285 Ile Arg Leu Arg Lys Arg Ser Val Lys Asn Pro Tyr Pro Ile Ser Phe 290 295 300 Leu Leu Ser Asp Leu Ile Asn Arg Arg Thr Gln Arg Val Asp Gly Gln 305 310 315 320 Pro Met Tyr Gly Met Glu Ser Gln Val Glu Glu Val Arg Val Phe Asp 325 330 335 Gly Thr Glu Lys Leu Pro Gly Asp Pro Asp Met Ile Arg Tyr Ile Asp 340 345 350 Lys Gln Gly Gln Leu Gln Thr Lys Met Leu 355 360 96362PRTBK virus 96Met Ala Pro Thr Lys Arg Lys Gly Glu Cys Pro Gly Ala Ala Pro Lys 1 5 10 15 Lys Pro Lys Asp Pro Val Gln Val Pro Lys Leu Leu Ile Lys Gly Gly 20 25 30 Val Glu Val Leu Glu Val Lys Thr Gly Val Asp Ala Ile Thr Glu Val 35 40 45 Glu Cys Phe Leu Asn Pro Glu Met Gly Asp Pro Asp Glu Asn Leu Arg 50 55 60 Gly Phe Ser Leu Lys Leu Ser Ala Glu Asn Asp Phe Ser Ser Asp Ser 65 70 75 80 Pro Glu Arg Lys Met Leu Pro Cys Tyr Ser Thr Ala Arg Ile Pro Leu 85 90 95 Pro Asn Leu Asn Glu Asp Leu Thr Cys Gly Asn Leu Leu Met Trp Glu 100 105 110 Ala Val Thr Val Gln Thr Glu Val Ile Gly Ile Thr Ser Met Leu Asn 115 120 125 Leu His Ala Gly Ser Gln Lys Val His Glu His Gly Gly Gly Lys Pro 130 135 140 Ile Gln Gly Ser Asn Phe His Phe Phe Ala Val Gly Gly Asp Pro Leu 145 150 155 160 Glu Met Gln Gly Val Leu Met Asn Tyr Arg Thr Lys Tyr Pro Glu Gly 165 170 175 Thr Ile Thr Pro Lys Asn Pro Thr Ala Gln Ser Gln Val Met Asn Thr 180 185 190 Asp His Lys Ala Tyr Leu Asp Lys Asn Asn Ala Tyr Pro Val Glu Cys 195 200 205 Trp Ile Pro Asp Pro Ser Arg Asn Glu Asn Thr Arg Tyr Phe Gly Thr 210 215 220 Leu Thr Gly Gly Glu Asn Val Pro Pro Val Leu His Val Thr Asn Thr 225 230 235 240 Ala Thr Thr Val Leu Leu Asp Glu Gln Gly Val Gly Pro Leu Cys Lys 245 250 255 Ala Asp Ser Leu Tyr Val Ser Ala Ala Asp Ile Cys Gly Leu Phe Thr 260 265 270 Asn Ser Ser Gly Thr Gln Gln Trp Arg Gly Leu Ala Arg Tyr Phe Lys 275 280 285 Ile Arg Leu Arg Lys Arg Ser Val Lys Asn Pro Tyr Pro Ile Ser Phe 290 295 300 Leu Leu Ser Asp Leu Ile Asn Arg Arg Thr Gln Arg Val Asp Gly Gln 305 310 315 320 Pro Met Tyr Gly Met Glu Ser Gln Val Glu Glu Val Arg Val Phe Asp 325 330 335 Gly Thr Glu Lys Leu Pro Gly Asp Pro Asp Met Ile Arg Tyr Ile Asp 340 345 350 Lys Gln Gly Gln Leu Gln Thr Lys Met Leu 355 360 97362PRTBK virus 97Met Ala Pro Thr Lys Arg Lys Gly Glu Cys Pro Gly Ala Ala Pro Lys 1 5 10 15 Lys Pro Lys Asp Pro Val Gln Val Pro Lys Leu Leu Ile Lys Gly Gly 20 25 30 Val Glu Val Leu Glu Val Lys Thr Gly Val Asp Ala Ile Thr Glu Val 35 40 45 Glu Cys Phe Leu Asn Pro Glu Met Gly Asp Pro Asn Glu Asn Leu Arg 50 55 60 Gly Phe Ser Leu Lys Leu Ser Ala Glu Asn Asp Phe Ser Ser Asp Ser 65 70 75 80 Pro Glu Arg Lys Met Leu Pro Cys Tyr Ser Thr Ala Arg Ile Pro Leu 85 90 95 Pro Asn Leu Asn Glu Asp Leu Thr Cys Gly Asn Leu Leu Met Trp Glu 100 105 110 Ala Val Thr Val Gln Thr Glu Val Ile Gly Ile Thr Ser Met Leu Asn 115 120 125 Leu His Ala Gly Ser Gln Lys Val His Glu His Gly Gly Gly Lys Pro 130 135 140 Ile Gln Gly Ser Asn Phe His Phe Phe Ala Val Gly Gly Asp Pro Leu 145 150 155 160 Glu Met Gln Gly Val Leu Met Asn Tyr Arg Thr Lys Tyr Pro Glu Gly 165 170 175 Thr Ile Thr Pro Lys Asn Pro Thr Ala Gln Ser Gln Val Met Asn Thr 180 185 190 Asp His Lys Ala Tyr Leu Asp Lys Asn Asn Ala Tyr Pro Val Glu Cys 195 200 205 Trp Ile Pro Asp Pro Ser Arg Asn Glu Asn Thr Arg Tyr Phe Gly Thr 210 215 220 Leu Thr Gly Gly Glu Asn Val Pro Pro Val Leu His Val Thr Asn Thr 225 230 235 240 Ala Thr Thr Val Leu Leu Asp Glu Gln Gly Val Gly Pro Leu Cys Lys 245 250 255 Ala Asp Ser Leu Tyr Val Ser Ala Ala Asp Ile Cys Gly Leu Phe Thr 260 265 270 Asn Ser Ser Gly Thr Gln Gln Trp Arg Gly Leu Ala Arg Tyr Phe Lys 275 280 285 Ile Arg Leu Arg Lys Arg Ser Val Lys Asn Pro Tyr Pro Ile Ser Phe 290 295 300 Leu Leu Ser Asp Leu Ile Asn Arg Arg Thr Gln Arg Val Asp Gly Gln 305 310 315 320 Pro Met Tyr Gly Met Glu Ser Gln Val Glu Glu Val Arg Val Phe Asp 325 330 335 Gly Thr Glu Lys Leu Pro Gly Asp Pro Asp Met Ile Arg Tyr Ile Asp 340 345 350 Lys Gln Gly Gln Leu Gln Thr Lys Met Leu 355 360 98362PRTBK virus 98Met Ala Pro Thr Lys Arg Lys Gly Glu Cys Pro Gly Ala Ala Pro Lys 1 5 10 15 Lys Pro Lys Asp Pro Val Gln Val Pro Lys Leu Leu Ile Lys Gly Gly 20 25 30 Val Glu Val Leu Glu Val Lys Thr Gly Val Asp Ala Ile Thr Glu Val 35 40 45 Glu Cys Phe Leu Asn Pro Glu Met Gly Asp Pro Asp Glu Asn Leu Arg 50 55 60 Gly Phe Ser Leu Lys Leu Ser Ala Glu Asn Asp Phe Ser Ser Asp Ser 65 70 75 80 Pro Gln Arg Lys Met Leu Pro Cys Tyr Ser Thr Ala Arg Ile Pro Leu 85 90 95 Pro Asn Leu Asn Glu Asp Leu Thr Cys Gly Asn Leu Leu Met Trp Glu 100 105 110 Ala Val Thr Val Gln Thr Glu Val Ile Gly Ile Thr Ser Met Leu Asn 115 120 125 Leu His Ala Gly Ser Gln Lys Val His Glu His Gly Gly Gly Lys Pro 130 135 140 Ile Gln Gly Ser Asn Phe His Phe Phe Ala Val Gly Gly Asp Pro Leu 145 150 155 160 Glu Met Gln Gly Val Leu Met Asn Tyr Arg Thr Lys Tyr Pro Glu Gly 165 170 175 Thr Ile Thr Pro Lys Asn Pro Thr Ala Gln Ser Gln Val Met Asn Thr 180 185 190 Asp His Lys Ala Tyr Leu Asp Lys Asn Asn Ala Tyr Pro Val Glu Cys 195 200 205 Trp Ile Pro Asp Pro Ser Arg Asn Glu Asn Thr Arg Tyr Phe Gly Thr 210 215 220 Leu Thr Gly Gly Glu Asn Val Pro Pro Val Leu His Val Thr Asn Thr 225 230 235 240 Ala Thr Thr Val Leu Leu Asp Glu Gln Gly Val Gly Pro Leu Cys Lys 245 250 255 Ala Asp Ser Leu Tyr Val Ser Ala Ala Asp Ile Cys Gly Leu Phe Thr 260 265 270 Asn Ser Ser Gly Thr Gln Gln Trp Arg Gly Leu Ala Arg Tyr Phe Lys 275 280 285 Ile Arg Leu Arg Lys Arg Ser Val Lys Asn Pro Tyr Pro Ile Ser Phe 290 295 300 Leu Leu Ser Asp Leu Ile Asn Arg Arg Thr Gln Arg Val Asp Gly Gln 305 310 315 320 Pro Met Tyr Gly Met Glu Ser Gln Val Glu Glu Val Arg Val Phe Asp 325 330 335 Gly Thr Glu Lys Leu Pro Gly Asp Pro Asp Met Ile Arg Tyr Ile Asp 340 345 350 Lys Gln Gly Gln Leu Gln Thr Lys Met Leu 355 360 99362PRTBK virus 99Met Ala Pro Thr Lys Arg Lys Gly Glu Cys Pro Gly Ala Ala Pro Lys 1 5 10 15 Lys Pro Lys Asp Pro Val Gln Val Pro Lys Leu Leu Ile Lys Gly Gly 20 25 30 Val Glu Val Leu Glu Val Lys Thr Gly Val Asp Ala Ile Thr Glu Val 35 40 45 Glu Cys Phe Leu Asn Pro Glu Met Gly Asp Pro Asp Glu Asn Leu Arg 50 55 60 Gly Phe Ser Leu Lys Leu Ser Ala Glu Asn Asp Phe Ser Ser Asp Ser 65 70 75 80 Pro Asp Arg Lys Met Leu Pro Cys Tyr Ser Thr Ala Arg Ile Pro Leu 85 90 95 Pro Asn Leu Asn Glu Asp Leu Thr Cys Gly Asn Leu Leu Met Trp Glu 100 105 110 Ala Val Thr Val Gln Thr Glu Val Ile Gly Ile Thr Ser Met Leu Asn 115 120 125 Leu His Ala Gly Ser Gln Lys Val His Glu His Gly Gly Gly Lys Pro 130 135 140 Ile Gln Gly Ser Asn Phe His Phe Phe Ala Val Gly Gly Asp Pro Leu 145 150 155 160 Glu Met Gln Gly Val Leu Met Asn Tyr Arg Thr Lys Tyr Pro Glu Gly 165 170 175 Thr Ile Thr Pro Lys Asn Pro Thr Ala Gln Ser Gln Val Met Asn Thr 180 185 190 Asp His Lys Ala Tyr Leu Asp Lys Asn Asn Ala Tyr Pro Val Glu Cys 195 200 205 Trp Ile Pro Asp Pro Ser Arg Asn Glu Asn Thr Arg Tyr Phe Gly Thr 210 215 220 Leu Thr Gly Gly Glu Asn Val Pro Pro Val Leu His Val Thr Asn Thr 225 230 235 240 Ala Thr Thr Val Leu Leu Asp Glu Gln Gly Val Gly Pro Leu Cys Lys 245 250 255 Ala Asp Ser Leu Tyr Val Ser Ala Ala Asp Ile Cys Gly Leu Phe Thr 260 265 270 Asn Ser Ser Gly Thr Gln Gln Trp Arg Gly Leu Ala Arg Tyr Phe Lys 275 280 285 Ile Arg Leu Arg Lys Arg Ser Val Lys Asn Pro Tyr Pro Ile Ser Phe 290 295 300 Leu Leu Ser Asp Leu Ile Asn Arg Arg Thr Gln Arg Val Asp Gly Gln 305 310 315 320 Pro Met Tyr Gly Met Glu Ser Gln Val Glu Glu Val Arg Val Phe Asp 325 330 335 Gly Thr Glu Lys Leu Pro Gly Asp Pro Asp Met Ile Arg Tyr Ile Asp 340 345 350 Lys Gln Gly Gln Leu Gln Thr Lys Met Leu 355 360 100362PRTBK virus 100Met Ala Pro Thr Lys Arg Lys Gly Glu Cys Pro Gly Ala Ala Pro Lys 1 5 10 15 Lys Pro Lys Glu Pro Val Gln Val Pro Lys Leu Leu Ile Lys Gly Gly 20 25 30 Val Glu Val Leu Glu Val Lys Thr Gly Val Asp Ala Ile Thr Glu Val 35 40 45 Glu Cys Phe Leu Asn Pro Glu Met Gly Asp Pro Asp Glu Asn Leu Arg 50 55 60 Gly Phe Ser Leu Lys Leu Ser Ala Glu Asn Asp Phe Ser Ser Asp Ser 65 70 75 80 Pro Glu Arg Lys Met Leu Pro Cys Tyr Ser Thr Ala Arg Ile Pro Leu 85 90 95 Pro Asn Leu Asn Glu Asp Leu Thr Cys Gly Asn Leu Leu Met Trp Glu 100 105 110 Ala Val Thr Val Gln Thr Glu Val Ile Gly Ile Thr Ser Met Leu Asn 115 120 125 Leu His Ala Gly Ser Gln Lys Val His Glu His Gly Gly Gly Lys Pro 130 135 140 Ile Gln Gly Ser Asn Phe His Phe Phe Ala Val Gly Gly Asp Pro Leu 145 150 155 160 Glu Met Gln Gly Val Leu Met Asn Tyr Arg Thr Lys Tyr Pro Glu Gly 165 170 175 Thr Ile Thr Pro Lys Asn Pro Thr Ala Gln Ser Gln Val Met Asn Thr 180 185 190 Asp His Lys Ala Tyr Leu Asp Lys Asn Asn Ala Tyr Pro Val Glu Cys 195 200 205 Trp Ile Pro Asp Pro Ser Arg Asn Glu Asn Thr Arg Tyr Phe Gly Thr 210 215 220 Leu Thr Gly Gly Glu Asn Val Pro Pro Val Leu His Val Thr Asn Thr 225 230 235 240 Ala Thr Thr Val Leu Leu Asp Glu Gln Gly Val Gly Pro Leu Cys Lys 245 250 255 Ala Asp Ser Leu Tyr Val Ser Ala Ala Asp Ile Cys Gly Leu Phe Thr 260 265 270 Asn Ser Ser Gly Thr Gln Gln Trp Arg Gly Leu Ala Arg Tyr Phe Lys 275 280 285 Ile Arg Leu Arg Lys Arg Ser Val Lys Asn Pro Tyr Pro Ile Ser Phe 290 295 300 Leu Leu Ser Asp Leu Ile Asn Arg Arg Thr Gln Arg Val Asp Gly Gln 305 310 315 320 Pro Met Tyr Gly Met Glu Ser Gln Val Glu Glu Val Arg Val Phe Asp 325 330 335 Gly Thr Glu Lys Leu Pro Gly Asp Pro Asp Met Ile Arg Tyr Ile Asp 340 345 350 Lys Gln Gly Gln Leu Gln Thr Lys Met Leu 355 360 101362PRTBK virus 101Met Ala Pro Thr Lys Arg Lys Gly Glu Cys Pro Gly Ala Ala Pro Lys 1 5 10 15 Lys Pro Lys Asp Pro Val Gln Val Pro Lys Leu Leu Ile Lys Gly Gly 20 25 30 Val Glu Val Leu Glu Val Lys Thr Gly Val Asp Ala Ile Thr Glu Val 35 40 45 Glu Cys Phe Leu Asn Pro Glu Met Gly Asp Pro Asp Glu Asn Leu Arg 50 55 60 Gly Phe Ser Leu Lys Leu Ser Ala Glu Asn Asp Phe Ser Ser Asp Ser 65 70 75 80 Pro Glu Arg Lys Met Leu Pro Cys Tyr Ser Thr Ala Arg Ile Pro Leu 85 90 95 Pro Asn Leu Asn Glu Asp Leu Thr Cys Gly Asn Leu Leu Met Trp Glu 100 105 110 Ala Val Thr Val Gln Thr Glu Val Ile Gly Ile Thr Ser Met Leu Asn 115 120 125 Leu

His Ala Gly Ser Gln Lys Val His Glu His Gly Gly Gly Lys Pro 130 135 140 Ile Gln Gly Ser Asn Phe His Phe Phe Ala Val Gly Gly Asp Pro Leu 145 150 155 160 Glu Met Gln Gly Val Leu Met Asn Tyr Arg Thr Lys Tyr Pro Glu Gly 165 170 175 Thr Ile Thr Pro Lys Asn Pro Thr Ala Gln Ser Gln Val Met Asn Thr 180 185 190 Asp His Lys Ala Tyr Leu Asp Lys Asn Asn Ala Tyr Pro Val Glu Cys 195 200 205 Trp Ile Pro Asp Pro Ser Arg Asn Glu Asn Thr Arg Tyr Phe Gly Thr 210 215 220 Phe Thr Gly Gly Glu Asn Val Pro Pro Val Leu His Val Thr Asn Thr 225 230 235 240 Ala Thr Thr Val Leu Leu Asp Glu Gln Gly Val Gly Pro Leu Cys Lys 245 250 255 Ala Asp Ser Leu Tyr Val Ser Ala Ala Asp Ile Cys Gly Leu Phe Thr 260 265 270 Asn Ser Ser Gly Thr Gln Gln Trp Arg Gly Leu Ala Arg Tyr Phe Lys 275 280 285 Ile Arg Leu Arg Lys Arg Ser Val Lys Asn Pro Tyr Pro Ile Ser Phe 290 295 300 Leu Leu Ser Asp Leu Ile Asn Arg Arg Thr Gln Arg Val Asp Gly Gln 305 310 315 320 Pro Met Tyr Gly Met Glu Ser Gln Val Glu Glu Val Arg Val Phe Asp 325 330 335 Gly Thr Glu Lys Leu Pro Gly Asp Pro Asp Met Ile Arg Tyr Ile Asp 340 345 350 Lys Gln Gly Gln Leu Gln Thr Lys Met Leu 355 360 102362PRTBK virus 102Met Ala Pro Thr Lys Arg Lys Gly Glu Cys Pro Gly Ala Ala Pro Lys 1 5 10 15 Lys Pro Lys Glu Pro Val Gln Val Pro Lys Leu Leu Ile Lys Gly Gly 20 25 30 Val Glu Val Leu Glu Val Lys Thr Gly Val Asp Ala Ile Thr Glu Val 35 40 45 Glu Cys Phe Leu Asn Pro Glu Met Gly Asp Pro Asp Glu Asn Leu Arg 50 55 60 Gly Phe Ser Leu Lys Leu Ser Ala Glu Asn Asp Phe Ser Ser Asp Ser 65 70 75 80 Pro Glu Arg Lys Met Leu Pro Cys Tyr Ser Thr Ala Arg Ile Pro Leu 85 90 95 Pro Asn Leu Asn Glu Asp Leu Thr Cys Gly Asn Leu Leu Met Trp Glu 100 105 110 Ala Val Thr Val Gln Thr Glu Val Ile Gly Ile Thr Ser Met Leu Asn 115 120 125 Leu His Ala Gly Ser Gln Lys Val His Glu His Gly Gly Gly Lys Pro 130 135 140 Ile Gln Gly Ser Asn Phe His Phe Phe Ala Val Gly Gly Asp Pro Leu 145 150 155 160 Glu Met Gln Gly Val Leu Met Asn Tyr Arg Thr Lys Tyr Pro Glu Gly 165 170 175 Thr Ile Thr Pro Lys Asn Pro Thr Ala Gln Ser Gln Val Met Asn Thr 180 185 190 Asp His Lys Ala Tyr Leu Asp Lys Asn Asn Ala Tyr Pro Val Glu Cys 195 200 205 Trp Ile Pro Asp Pro Ser Arg Asn Glu Asn Thr Arg Tyr Phe Gly Thr 210 215 220 Phe Thr Gly Gly Glu Asn Val Pro Pro Val Leu His Val Thr Asn Thr 225 230 235 240 Ala Thr Thr Val Leu Leu Asp Glu Gln Gly Val Gly Pro Leu Cys Lys 245 250 255 Ala Asp Ser Leu Tyr Val Ser Ala Ala Asp Ile Cys Gly Leu Phe Thr 260 265 270 Asn Ser Ser Gly Thr Gln Gln Trp Arg Gly Leu Ala Arg Tyr Phe Lys 275 280 285 Ile Arg Leu Arg Lys Arg Ser Val Lys Asn Pro Tyr Pro Ile Ser Phe 290 295 300 Leu Leu Ser Asp Leu Ile Asn Arg Arg Thr Gln Arg Val Asp Gly Gln 305 310 315 320 Pro Met Tyr Gly Met Glu Ser Gln Val Glu Glu Val Arg Val Phe Asp 325 330 335 Gly Thr Glu Lys Leu Pro Gly Asp Pro Asp Met Ile Arg Tyr Ile Asp 340 345 350 Lys Gln Gly Gln Leu Gln Thr Lys Met Leu 355 360 103362PRTBK virus 103Met Ala Pro Thr Lys Arg Lys Gly Glu Cys Pro Gly Ala Ala Pro Lys 1 5 10 15 Lys Pro Lys Glu Pro Val Gln Val Pro Lys Leu Leu Ile Lys Gly Gly 20 25 30 Val Glu Val Leu Glu Val Lys Thr Gly Val Asp Ala Ile Thr Glu Val 35 40 45 Glu Cys Phe Leu Asn Pro Glu Met Gly Asp Pro Asp Glu Asn Leu Arg 50 55 60 Gly Phe Ser Leu Lys Leu Ser Val Glu Asn Asp Phe Ser Ser Asp Ser 65 70 75 80 Pro Gln Arg Lys Met Leu Pro Cys Tyr Ser Thr Ala Arg Ile Pro Leu 85 90 95 Pro Asn Leu Asn Glu Asp Leu Thr Cys Gly Asn Leu Leu Met Trp Glu 100 105 110 Ala Val Thr Val Gln Thr Glu Val Ile Gly Ile Thr Ser Met Leu Asn 115 120 125 Leu His Ala Gly Ser Gln Lys Val His Glu His Gly Gly Gly Lys Pro 130 135 140 Ile Gln Gly Ser Asn Phe His Phe Phe Ala Val Gly Gly Asp Pro Leu 145 150 155 160 Glu Met Gln Gly Val Leu Met Asn Tyr Arg Thr Lys Tyr Pro Glu Gly 165 170 175 Thr Ile Thr Pro Lys Asn Pro Thr Ala Gln Ser Gln Val Met Asn Thr 180 185 190 Asp His Lys Ala Tyr Leu Asp Lys Asn Asn Ala Tyr Pro Val Glu Cys 195 200 205 Trp Ile Pro Asp Pro Ser Arg Asn Glu Asn Thr Arg Tyr Phe Gly Thr 210 215 220 Leu Thr Gly Gly Glu Asn Val Pro Pro Val Leu His Val Thr Asn Thr 225 230 235 240 Ala Thr Thr Val Leu Leu Asp Glu Gln Gly Val Gly Pro Leu Cys Lys 245 250 255 Ala Asp Ser Leu Tyr Val Ser Ala Ala Asp Ile Cys Gly Leu Phe Thr 260 265 270 Asn Ser Ser Gly Thr Gln Gln Trp Arg Gly Leu Ala Arg Tyr Phe Lys 275 280 285 Ile Arg Leu Arg Lys Arg Ser Val Lys Asn Pro Tyr Pro Ile Ser Phe 290 295 300 Leu Leu Ser Asp Leu Ile Asn Arg Arg Thr Gln Arg Val Asp Gly Gln 305 310 315 320 Pro Met Tyr Gly Met Glu Ser Gln Val Glu Glu Val Arg Val Phe Asp 325 330 335 Gly Thr Glu Lys Leu Pro Gly Asp Pro Asp Met Ile Arg Tyr Ile Asp 340 345 350 Lys Gln Gly Gln Leu Gln Thr Lys Met Leu 355 360 104362PRTBK virus 104Met Ala Pro Thr Lys Arg Lys Gly Glu Cys Pro Gly Ala Ala Pro Lys 1 5 10 15 Lys Pro Lys Glu Pro Val Gln Val Pro Lys Leu Leu Ile Lys Gly Gly 20 25 30 Val Glu Val Leu Glu Val Lys Thr Gly Val Asp Ala Ile Thr Glu Val 35 40 45 Glu Cys Phe Leu Asn Pro Glu Met Gly Asp Pro Asp Glu Asn Leu Arg 50 55 60 Gly Tyr Ser Leu Lys Leu Thr Ala Glu Asn Ala Phe Asp Ser Asp Ser 65 70 75 80 Pro Asp Lys Lys Met Leu Pro Cys Tyr Ser Thr Ala Arg Ile Pro Leu 85 90 95 Pro Asn Leu Asn Glu Asp Leu Thr Cys Gly Asn Leu Leu Met Trp Glu 100 105 110 Ala Val Thr Val Lys Thr Glu Val Ile Gly Ile Thr Ser Met Leu Asn 115 120 125 Leu His Ala Gly Ser Gln Lys Val His Glu Asn Gly Gly Gly Lys Pro 130 135 140 Val Gln Gly Ser Asn Phe His Phe Phe Ala Val Gly Gly Asp Pro Leu 145 150 155 160 Glu Met Gln Gly Val Leu Met Asn Tyr Arg Thr Lys Tyr Pro Gln Gly 165 170 175 Thr Ile Thr Pro Lys Asn Pro Thr Ala Gln Ser Gln Val Met Asn Thr 180 185 190 Asp His Lys Ala Tyr Leu Asp Lys Asn Asn Ala Tyr Pro Val Glu Cys 195 200 205 Trp Ile Pro Asp Pro Ser Arg Asn Glu Asn Thr Arg Tyr Phe Gly Thr 210 215 220 Tyr Thr Gly Gly Glu Asn Val Pro Pro Val Leu His Val Thr Asn Thr 225 230 235 240 Ala Thr Thr Val Leu Leu Asp Glu Gln Gly Val Gly Pro Leu Cys Lys 245 250 255 Ala Asp Ser Leu Tyr Val Ser Ala Ala Asp Ile Cys Gly Leu Phe Thr 260 265 270 Asn Ser Ser Gly Thr Gln Gln Trp Arg Gly Leu Ala Arg Tyr Phe Lys 275 280 285 Ile Arg Leu Arg Lys Arg Ser Val Lys Asn Pro Tyr Pro Ile Ser Phe 290 295 300 Leu Leu Ser Asp Leu Ile Asn Arg Arg Thr Gln Lys Val Asp Gly Gln 305 310 315 320 Pro Met Tyr Gly Met Glu Ser Gln Val Glu Glu Val Arg Val Phe Asp 325 330 335 Gly Thr Glu Gln Leu Pro Gly Asp Pro Asp Met Ile Arg Tyr Ile Asp 340 345 350 Arg Gln Gly Gln Leu Gln Thr Lys Met Val 355 360 105362PRTBK virus 105Met Ala Pro Thr Lys Arg Lys Gly Glu Cys Pro Gly Ala Ala Pro Lys 1 5 10 15 Lys Pro Lys Glu Pro Val Gln Val Pro Lys Leu Leu Ile Lys Gly Gly 20 25 30 Val Glu Val Leu Glu Val Lys Thr Gly Val Asp Ala Ile Thr Glu Val 35 40 45 Glu Cys Phe Leu Asn Pro Glu Met Gly Asp Pro Asp Asn Asp Leu Arg 50 55 60 Gly Tyr Ser Leu Lys Leu Thr Ala Glu Asn Ala Phe Asp Ser Asp Ser 65 70 75 80 Pro Asp Lys Lys Met Leu Pro Cys Tyr Ser Thr Ala Arg Ile Pro Leu 85 90 95 Pro Asn Leu Asn Glu Asp Leu Thr Cys Gly Asn Leu Leu Met Trp Glu 100 105 110 Ala Val Thr Val Lys Thr Glu Val Ile Gly Ile Thr Ser Met Leu Asn 115 120 125 Leu His Ala Gly Ser Gln Lys Val His Glu Asn Gly Gly Gly Lys Pro 130 135 140 Val Gln Gly Ser Asn Phe His Phe Phe Ala Val Gly Gly Asp Pro Leu 145 150 155 160 Glu Met Gln Gly Val Leu Met Asn Tyr Arg Thr Lys Tyr Pro Gln Gly 165 170 175 Thr Ile Thr Pro Lys Asn Pro Thr Ala Gln Ser Gln Val Met Asn Thr 180 185 190 Asp His Lys Ala Tyr Leu Asp Lys Asn Asn Ala Tyr Pro Val Glu Cys 195 200 205 Trp Ile Pro Asp Pro Ser Arg Asn Glu Asn Thr Arg Tyr Phe Gly Thr 210 215 220 Tyr Thr Gly Gly Glu Asn Val Pro Pro Val Leu His Val Thr Asn Thr 225 230 235 240 Ala Thr Thr Val Leu Leu Asp Glu Gln Gly Val Gly Pro Leu Cys Lys 245 250 255 Ala Asp Ser Leu Tyr Val Ser Ala Ala Asp Ile Cys Gly Leu Phe Thr 260 265 270 Asn Ser Ser Gly Thr Gln Gln Trp Arg Gly Leu Ala Arg Tyr Phe Lys 275 280 285 Ile Arg Leu Arg Lys Arg Ser Val Lys Asn Pro Tyr Pro Ile Ser Phe 290 295 300 Leu Leu Ser Asp Leu Ile Asn Arg Arg Thr Gln Lys Val Asp Gly Gln 305 310 315 320 Pro Met Tyr Gly Met Glu Ser Gln Val Glu Glu Val Arg Val Phe Asp 325 330 335 Gly Thr Glu Gln Leu Pro Gly Asp Pro Asp Met Ile Arg Tyr Ile Asp 340 345 350 Arg Gln Gly Gln Leu Gln Thr Lys Met Val 355 360 106362PRTBK virus 106Met Ala Pro Thr Lys Arg Lys Gly Glu Cys Pro Gly Ala Ala Pro Lys 1 5 10 15 Lys Pro Lys Glu Pro Val Gln Val Pro Lys Leu Leu Ile Lys Gly Gly 20 25 30 Val Glu Val Leu Glu Val Lys Thr Gly Val Asp Ala Ile Thr Glu Val 35 40 45 Glu Cys Phe Leu Asn Pro Glu Met Gly Asp Pro Asp Asp Asn Leu Arg 50 55 60 Gly Tyr Ser Leu Lys Leu Thr Ala Glu Asn Ala Phe Asp Ser Asp Ser 65 70 75 80 Pro Asp Lys Lys Met Leu Pro Cys Tyr Ser Thr Ala Arg Ile Pro Leu 85 90 95 Pro Asn Leu Asn Glu Asp Leu Thr Cys Gly Asn Leu Leu Met Trp Glu 100 105 110 Ala Val Thr Val Lys Thr Glu Val Ile Gly Ile Thr Ser Met Leu Asn 115 120 125 Leu His Ala Gly Ser Gln Lys Val His Glu Asn Gly Gly Gly Lys Pro 130 135 140 Val Gln Gly Ser Asn Phe His Phe Phe Ala Val Gly Gly Asp Pro Leu 145 150 155 160 Glu Met Gln Gly Val Leu Met Asn Tyr Arg Thr Lys Tyr Pro Gln Gly 165 170 175 Thr Ile Thr Pro Lys Asn Pro Thr Ala Gln Ser Gln Val Met Asn Thr 180 185 190 Asp His Lys Ala Tyr Leu Asp Lys Asn Asn Ala Tyr Pro Val Glu Cys 195 200 205 Trp Ile Pro Asp Pro Ser Arg Asn Glu Asn Thr Arg Tyr Phe Gly Thr 210 215 220 Tyr Thr Gly Gly Glu Asn Val Pro Pro Val Leu His Val Thr Asn Thr 225 230 235 240 Ala Thr Thr Val Leu Leu Asp Glu Gln Gly Val Gly Pro Leu Cys Lys 245 250 255 Ala Asp Ser Leu Tyr Val Ser Ala Ala Asp Ile Cys Gly Leu Phe Thr 260 265 270 Asn Ser Ser Gly Thr Gln Gln Trp Arg Gly Leu Ala Arg Tyr Phe Lys 275 280 285 Ile Arg Leu Arg Lys Arg Ser Val Lys Asn Pro Tyr Pro Ile Ser Phe 290 295 300 Leu Leu Ser Asp Leu Ile Asn Arg Arg Thr Gln Lys Val Asp Gly Gln 305 310 315 320 Pro Met Tyr Gly Met Glu Ser Gln Val Glu Glu Val Arg Val Phe Asp 325 330 335 Gly Thr Glu Gln Leu Pro Gly Asp Pro Asp Met Ile Arg Tyr Ile Asp 340 345 350 Arg Gln Gly Gln Leu Gln Thr Lys Met Val 355 360 107362PRTBK virus 107Met Ala Pro Thr Lys Arg Lys Gly Glu Cys Pro Gly Ala Ala Pro Lys 1 5 10 15 Lys Pro Lys Glu Pro Val Gln Val Pro Lys Leu Leu Ile Lys Gly Gly 20 25 30 Val Glu Val Leu Glu Val Lys Thr Gly Val Asp Ala Ile Thr Glu Val 35 40 45 Glu Cys Phe Leu Asn Pro Glu Met Gly Asp Pro Asp Asp His Leu Arg 50 55 60 Gly Tyr Ser Gln His Leu Thr Ala Glu Asn Ala Phe Asp Ser Asp Ser 65 70 75 80 Pro Asp Lys Lys Met Leu Pro Cys Tyr Ser Thr Ala Arg Ile Pro Leu 85 90 95 Pro Asn Leu Asn Glu Asp Leu Thr Cys Gly Asn Leu Leu Met Trp Glu 100 105 110 Ala Val Thr Val Lys Thr Glu Val Ile Gly Ile Thr Ser Met Leu Asn 115 120 125 Leu His Ala Gly Ser Gln Lys Val His Glu Asn Gly Gly Gly Lys Pro 130 135 140 Val Gln Gly Ser Asn Phe His Phe Phe Ala Val Gly Gly Asp Pro Leu 145 150 155 160 Glu Met Gln Gly Val Leu Met Asn Tyr Arg Thr Lys Tyr Pro Gln Gly 165 170 175 Thr Ile Thr Pro Lys Asn Pro Thr Ala Gln Ser Gln Val Met Asn Thr 180 185 190 Asp His Lys Ala Tyr Leu Asp Lys Asn Asn Ala Tyr Pro Val Glu Cys 195 200 205 Trp Ile Pro Asp Pro Ser Lys Asn Glu Asn Thr Arg Tyr Phe Gly Thr 210 215 220 Tyr Thr Gly Gly Glu Asn Val Pro Pro Val Leu His Val Thr Asn Thr 225 230 235 240 Ala Thr Thr Val Leu Leu Asp Glu Gln Gly Val Gly Pro Leu Cys Lys

245 250 255 Ala Asp Ser Leu Tyr Val Ser Ala Ala Asp Ile Cys Gly Leu Phe Thr 260 265 270 Asn Ser Ser Gly Thr Gln Gln Trp Arg Gly Leu Ala Arg Tyr Phe Lys 275 280 285 Ile Arg Leu Arg Lys Arg Ser Val Lys Asn Pro Tyr Pro Ile Ser Phe 290 295 300 Leu Leu Ser Asp Leu Ile Asn Arg Arg Thr Gln Lys Val Asp Gly Gln 305 310 315 320 Pro Met Tyr Gly Met Glu Ser Gln Val Glu Glu Val Arg Val Phe Asp 325 330 335 Gly Thr Glu Gln Leu Pro Gly Asp Pro Asp Met Ile Arg Tyr Ile Asp 340 345 350 Arg Gln Gly Gln Leu Gln Thr Lys Met Val 355 360 108362PRTBK virus 108Met Ala Pro Thr Lys Arg Lys Gly Glu Cys Pro Gly Ala Ala Pro Lys 1 5 10 15 Lys Pro Lys Glu Pro Val Gln Val Pro Lys Leu Leu Ile Lys Gly Gly 20 25 30 Val Glu Val Leu Glu Val Lys Thr Gly Val Asp Ala Ile Thr Glu Val 35 40 45 Glu Cys Phe Leu Asn Pro Glu Met Gly Asp Pro Asp Asp Asn Leu Arg 50 55 60 Gly Tyr Ser Gln His Leu Ser Ala Glu Asn Ala Phe Glu Ser Asp Ser 65 70 75 80 Pro Asp Arg Lys Met Leu Pro Cys Tyr Ser Thr Ala Arg Ile Pro Leu 85 90 95 Pro Asn Leu Asn Glu Asp Leu Thr Cys Gly Asn Leu Leu Met Trp Glu 100 105 110 Ala Val Thr Val Lys Thr Glu Val Ile Gly Ile Thr Ser Met Leu Asn 115 120 125 Leu His Ala Gly Ser Gln Lys Val His Glu Asn Gly Gly Gly Lys Pro 130 135 140 Val Gln Gly Ser Asn Phe His Phe Phe Ala Val Gly Gly Asp Pro Leu 145 150 155 160 Glu Met Gln Gly Val Leu Met Asn Tyr Arg Thr Lys Tyr Pro Gln Gly 165 170 175 Thr Ile Thr Pro Lys Asn Pro Thr Ala Gln Ser Gln Val Met Asn Thr 180 185 190 Asp His Lys Ala Tyr Leu Asp Lys Asn Asn Ala Tyr Pro Val Glu Cys 195 200 205 Trp Ile Pro Asp Pro Ser Arg Asn Glu Asn Thr Arg Tyr Phe Gly Thr 210 215 220 Tyr Thr Gly Gly Glu Asn Val Pro Pro Val Leu His Val Thr Asn Thr 225 230 235 240 Ala Thr Thr Val Leu Leu Asp Glu Gln Gly Val Gly Pro Leu Cys Lys 245 250 255 Ala Asp Ser Leu Tyr Val Ser Ala Ala Asp Ile Cys Gly Leu Phe Thr 260 265 270 Asn Ser Ser Gly Thr Gln Gln Trp Arg Gly Leu Ala Arg Tyr Phe Lys 275 280 285 Ile Arg Leu Arg Lys Arg Ser Val Lys Asn Pro Tyr Pro Ile Ser Phe 290 295 300 Leu Leu Ser Asp Leu Ile Asn Arg Arg Thr Gln Lys Val Asp Gly Gln 305 310 315 320 Pro Met Tyr Gly Met Glu Ser Gln Val Glu Glu Val Arg Val Phe Asp 325 330 335 Gly Thr Glu Gln Leu Pro Gly Asp Pro Asp Met Ile Arg Tyr Ile Asp 340 345 350 Arg Gln Gly Gln Leu Gln Thr Lys Met Val 355 360 109362PRTBK virus 109Met Ala Pro Thr Lys Arg Lys Gly Glu Cys Pro Gly Ala Ala Pro Lys 1 5 10 15 Lys Pro Lys Glu Pro Val Gln Val Pro Lys Leu Leu Ile Lys Gly Gly 20 25 30 Val Glu Val Leu Glu Val Lys Thr Gly Val Asp Ala Ile Thr Glu Val 35 40 45 Glu Cys Phe Leu Asn Pro Glu Met Gly Asp Pro Asp Glu Asn Leu Arg 50 55 60 Gly Tyr Ser Gln His Leu Ser Ala Glu Asn Ala Phe Glu Ser Asp Ser 65 70 75 80 Pro Asp Arg Lys Met Leu Pro Cys Tyr Ser Thr Ala Arg Ile Pro Leu 85 90 95 Pro Asn Leu Asn Glu Asp Leu Thr Cys Gly Asn Leu Leu Met Trp Glu 100 105 110 Ala Val Thr Val Lys Thr Glu Val Ile Gly Ile Thr Ser Met Leu Asn 115 120 125 Leu His Ala Gly Ser Gln Lys Val His Glu Asn Gly Gly Gly Lys Pro 130 135 140 Val Gln Gly Ser Asn Phe His Phe Phe Ala Val Gly Gly Asp Pro Leu 145 150 155 160 Glu Met Gln Gly Val Leu Met Asn Tyr Arg Thr Lys Tyr Pro Gln Gly 165 170 175 Thr Ile Thr Pro Lys Asn Pro Thr Ala Gln Ser Gln Val Met Asn Thr 180 185 190 Asp His Lys Ala Tyr Leu Asp Lys Asn Asn Ala Tyr Pro Val Glu Cys 195 200 205 Trp Ile Pro Asp Pro Ser Arg Asn Glu Asn Thr Arg Tyr Phe Gly Thr 210 215 220 Tyr Thr Gly Gly Glu Asn Val Pro Pro Val Leu His Val Thr Asn Thr 225 230 235 240 Ala Thr Thr Val Leu Leu Asp Glu Gln Gly Val Gly Pro Leu Cys Lys 245 250 255 Ala Asp Ser Leu Tyr Val Ser Ala Ala Asp Ile Cys Gly Leu Phe Thr 260 265 270 Asn Ser Ser Gly Thr Gln Gln Trp Arg Gly Leu Ala Arg Tyr Phe Lys 275 280 285 Ile Arg Leu Arg Lys Arg Ser Val Lys Asn Pro Tyr Pro Ile Ser Phe 290 295 300 Leu Leu Ser Asp Leu Ile Asn Arg Arg Thr Gln Lys Val Asp Gly Gln 305 310 315 320 Pro Met Tyr Gly Met Glu Ser Gln Val Glu Glu Val Arg Val Phe Asp 325 330 335 Gly Thr Glu Gln Leu Pro Gly Asp Pro Asp Met Ile Arg Tyr Ile Asp 340 345 350 Arg Gln Gly Gln Leu Gln Thr Lys Met Val 355 360 110362PRTBK virus 110Met Ala Pro Thr Lys Arg Lys Gly Glu Cys Pro Gly Ala Ala Pro Lys 1 5 10 15 Lys Pro Lys Glu Pro Val Gln Val Pro Lys Leu Leu Ile Lys Gly Gly 20 25 30 Val Glu Val Leu Glu Val Lys Thr Gly Val Asp Ala Ile Thr Glu Val 35 40 45 Glu Cys Phe Leu Asn Pro Glu Met Gly Asp Pro Asp Asn Asp Leu Arg 50 55 60 Gly Tyr Ser Leu Arg Leu Thr Ala Glu Thr Ala Phe Asp Ser Asp Ser 65 70 75 80 Pro Asp Arg Lys Met Leu Pro Cys Tyr Ser Thr Ala Arg Ile Pro Leu 85 90 95 Pro Asn Leu Asn Glu Asp Leu Thr Cys Gly Asn Leu Leu Met Trp Glu 100 105 110 Ala Val Thr Val Lys Thr Glu Val Ile Gly Ile Thr Ser Met Leu Asn 115 120 125 Leu His Ala Gly Ser Gln Lys Val His Glu Asn Gly Gly Gly Lys Pro 130 135 140 Ile Gln Gly Ser Asn Phe His Phe Phe Ala Val Gly Gly Asp Pro Leu 145 150 155 160 Glu Met Gln Gly Val Leu Met Asn Tyr Arg Thr Lys Tyr Pro Glu Gly 165 170 175 Thr Val Thr Pro Lys Asn Pro Thr Ala Gln Ser Gln Val Met Asn Thr 180 185 190 Asp His Lys Ala Tyr Leu Asp Lys Asn Asn Ala Tyr Pro Val Glu Cys 195 200 205 Trp Ile Pro Asp Pro Ser Arg Asn Glu Asn Thr Arg Tyr Phe Gly Thr 210 215 220 Tyr Thr Gly Gly Glu Asn Val Pro Pro Val Leu His Val Thr Asn Thr 225 230 235 240 Ala Thr Thr Val Leu Leu Asp Glu Gln Gly Val Gly Pro Leu Cys Lys 245 250 255 Ala Asp Ser Leu Tyr Val Ser Ala Ala Asp Ile Cys Gly Leu Phe Thr 260 265 270 Asn Ser Ser Gly Thr Gln Gln Trp Arg Gly Leu Pro Arg Tyr Phe Lys 275 280 285 Ile Arg Leu Arg Lys Arg Ser Val Lys Asn Pro Tyr Pro Ile Ser Phe 290 295 300 Leu Leu Ser Asp Leu Ile Asn Arg Arg Thr Gln Arg Val Asp Gly Gln 305 310 315 320 Pro Met Tyr Gly Met Glu Ser Gln Val Glu Glu Val Arg Val Phe Asp 325 330 335 Gly Thr Glu Gln Leu Pro Gly Asp Pro Asp Met Ile Arg Tyr Ile Asp 340 345 350 Arg Gln Gly Gln Leu Gln Thr Lys Met Val 355 360 111362PRTBK virus 111Met Ala Pro Thr Lys Arg Lys Gly Glu Cys Pro Gly Ala Ala Pro Lys 1 5 10 15 Lys Pro Lys Glu Pro Val Gln Val Pro Lys Leu Leu Ile Lys Gly Gly 20 25 30 Val Glu Val Leu Glu Val Lys Thr Gly Val Asp Ala Ile Thr Glu Val 35 40 45 Glu Cys Phe Leu Asn Pro Glu Met Gly Asp Pro Asp Asn Asp Leu Arg 50 55 60 Gly Tyr Ser Leu Arg Leu Thr Ala Glu Thr Ala Phe Asp Ser Asp Ser 65 70 75 80 Pro Asp Arg Lys Met Leu Pro Cys Tyr Ser Thr Ala Arg Ile Pro Leu 85 90 95 Pro Asn Leu Asn Glu Asp Leu Thr Cys Gly Asn Leu Leu Met Trp Glu 100 105 110 Ala Val Thr Val Lys Thr Glu Val Ile Gly Ile Thr Ser Met Leu Asn 115 120 125 Leu His Ala Gly Ser Gln Lys Val His Asp Asn Gly Gly Gly Lys Pro 130 135 140 Ile Gln Gly Ser Asn Phe His Phe Phe Ala Val Gly Gly Asp Pro Leu 145 150 155 160 Glu Met Gln Gly Val Leu Met Asn Tyr Arg Thr Lys Tyr Pro Glu Gly 165 170 175 Thr Val Thr Pro Lys Asn Pro Thr Ala Gln Ser Gln Val Met Asn Thr 180 185 190 Asp His Lys Ala Tyr Leu Asp Lys Asn Asn Ala Tyr Pro Val Glu Cys 195 200 205 Trp Ile Pro Asp Pro Ser Arg Asn Glu Asn Thr Arg Tyr Phe Gly Thr 210 215 220 Tyr Thr Gly Gly Glu Asn Val Pro Pro Val Leu His Val Thr Asn Thr 225 230 235 240 Ala Thr Thr Val Leu Leu Asp Glu Gln Gly Val Gly Pro Leu Cys Lys 245 250 255 Ala Asp Ser Leu Tyr Val Ser Ala Ala Asp Ile Cys Gly Leu Phe Thr 260 265 270 Asn Ser Ser Gly Thr Gln Gln Trp Arg Gly Leu Pro Arg Tyr Phe Lys 275 280 285 Ile Arg Leu Arg Lys Arg Ser Val Lys Asn Pro Tyr Pro Ile Ser Phe 290 295 300 Leu Leu Ser Asp Leu Ile Asn Arg Arg Thr Gln Arg Val Asp Gly Gln 305 310 315 320 Pro Met Tyr Gly Met Glu Ser Gln Val Glu Glu Val Arg Val Phe Asp 325 330 335 Gly Thr Glu Lys Leu Pro Gly Asp Pro Asp Met Ile Arg Tyr Ile Asp 340 345 350 Arg Gln Gly Gln Leu Gln Thr Lys Met Val 355 360 112362PRTBK virus 112Met Ala Pro Thr Lys Arg Lys Gly Glu Cys Pro Gly Ala Ala Pro Lys 1 5 10 15 Lys Pro Lys Glu Pro Val Gln Val Pro Lys Leu Leu Ile Lys Gly Gly 20 25 30 Val Glu Val Leu Glu Val Lys Thr Gly Val Asp Ala Ile Thr Glu Val 35 40 45 Glu Cys Phe Leu Asn Pro Glu Met Gly Asp Pro Asp Asn Asp Leu Arg 50 55 60 Gly Tyr Ser Leu Arg Leu Thr Ala Glu Thr Ala Phe Asp Ser Asp Ser 65 70 75 80 Pro Asp Arg Lys Met Leu Pro Cys Tyr Ser Thr Ala Arg Ile Pro Leu 85 90 95 Pro Asn Leu Asn Glu Asp Leu Thr Cys Gly Asn Leu Leu Met Trp Glu 100 105 110 Ala Val Thr Val Lys Thr Glu Val Met Gly Ile Thr Ser Met Leu Asn 115 120 125 Leu His Ala Gly Ser Gln Lys Val His Asp Asn Gly Gly Gly Lys Pro 130 135 140 Ile Gln Gly Ser Asn Phe His Phe Phe Ala Val Gly Gly Asp Pro Leu 145 150 155 160 Glu Met Gln Gly Val Leu Met Asn Tyr Arg Thr Lys Tyr Pro Glu Gly 165 170 175 Thr Val Thr Pro Lys Asn Pro Thr Ala Gln Ser Gln Val Met Asn Thr 180 185 190 Asp His Lys Ala Tyr Leu Asp Lys Asn Asn Ala Tyr Pro Val Glu Cys 195 200 205 Trp Ile Pro Asp Pro Ser Arg Asn Glu Asn Thr Arg Tyr Phe Gly Thr 210 215 220 Tyr Thr Gly Gly Glu Asn Val Pro Pro Val Leu His Val Thr Asn Thr 225 230 235 240 Ala Thr Thr Val Leu Leu Asp Glu Gln Gly Val Gly Pro Leu Cys Lys 245 250 255 Ala Asp Ser Leu Tyr Val Ser Ala Ala Asp Ile Cys Gly Leu Phe Thr 260 265 270 Asn Ser Ser Gly Thr Gln Gln Trp Arg Gly Leu Pro Arg Tyr Phe Lys 275 280 285 Ile Arg Leu Arg Lys Arg Ser Val Lys Asn Pro Tyr Pro Ile Ser Phe 290 295 300 Leu Leu Ser Asp Leu Ile Asn Arg Arg Thr Gln Arg Val Asp Gly Gln 305 310 315 320 Pro Met Tyr Gly Met Glu Ser Gln Val Glu Glu Val Arg Val Phe Asp 325 330 335 Gly Thr Glu Gln Leu Pro Gly Asp Pro Asp Met Ile Arg Tyr Ile Asp 340 345 350 Arg Gln Gly Gln Leu Gln Thr Lys Met Val 355 360 113362PRTBK virus 113Met Ala Pro Thr Lys Arg Lys Gly Glu Cys Pro Gly Ala Ala Pro Lys 1 5 10 15 Lys Pro Lys Glu Pro Val Gln Val Pro Lys Leu Leu Ile Lys Gly Gly 20 25 30 Val Glu Val Leu Glu Val Lys Thr Gly Val Asp Ala Ile Thr Glu Val 35 40 45 Glu Cys Phe Leu Asn Pro Glu Met Gly Asp Pro Asp Asn Asp Leu Arg 50 55 60 Gly Tyr Ser Leu Arg Leu Thr Ala Glu Thr Ala Phe Asp Ser Asp Ser 65 70 75 80 Pro Asp Arg Lys Met Leu Pro Cys Tyr Ser Thr Ala Arg Ile Pro Leu 85 90 95 Pro Asn Leu Asn Glu Asp Leu Thr Cys Gly Asn Leu Leu Met Trp Glu 100 105 110 Ala Val Thr Val Lys Thr Glu Val Met Gly Ile Thr Ser Met Leu Asn 115 120 125 Leu His Ala Gly Ser Gln Lys Val His Glu Asn Gly Gly Gly Lys Pro 130 135 140 Ile Gln Gly Ser Asn Phe His Phe Phe Ala Val Gly Gly Asp Pro Leu 145 150 155 160 Glu Met Gln Gly Val Leu Met Asn Tyr Arg Thr Lys Tyr Pro Glu Gly 165 170 175 Thr Val Thr Pro Lys Asn Pro Thr Ala Gln Ser Gln Val Met Asn Thr 180 185 190 Asp His Lys Ala Tyr Leu Asp Lys Asn Asn Ala Tyr Pro Val Glu Cys 195 200 205 Trp Ile Pro Asp Pro Ser Arg Asn Glu Asn Thr Arg Tyr Phe Gly Thr 210 215 220 Tyr Thr Gly Gly Glu Asn Val Pro Pro Val Leu His Val Thr Asn Thr 225 230 235 240 Ala Thr Thr Val Leu Leu Asp Glu Gln Gly Val Gly Pro Leu Cys Lys 245 250 255 Ala Asp Ser Leu Tyr Val Ser Ala Ala Asp Ile Cys Gly Leu Phe Thr 260 265 270 Asn Ser Ser Gly Thr Gln Gln Trp Arg Gly Leu Pro Arg Tyr Phe Lys 275 280 285 Ile Arg Leu Arg Lys Arg Ser Val Lys Asn Pro Tyr Pro Ile Ser Phe 290 295 300 Leu Leu Ser Asp Leu Ile Asn Arg Arg Thr Gln Arg Val Asp Gly Gln 305 310 315 320 Pro Met Tyr Gly Met Glu Ser Gln Val Glu Glu Val Arg Val Phe Asp 325 330 335 Gly Thr Glu Gln Leu Pro Gly Asp Pro Asp Met Ile Arg Tyr Ile Asp 340 345 350 Arg Gln Gly Gln Leu Gln Thr Lys Met Val 355 360 114362PRTBK virus 114Met Ala Pro Thr Lys Arg Lys

Gly Glu Cys Pro Gly Ala Ala Pro Lys 1 5 10 15 Lys Pro Lys Glu Pro Val Gln Val Pro Lys Leu Leu Ile Lys Gly Gly 20 25 30 Val Glu Val Leu Glu Val Lys Thr Gly Val Asp Ala Ile Thr Glu Val 35 40 45 Glu Cys Phe Leu Asn Pro Glu Met Gly Asp Pro Asp Asn Asp Leu Arg 50 55 60 Gly Tyr Ser Leu Arg Leu Thr Ala Glu Thr Ala Phe Asp Ser Asp Ser 65 70 75 80 Pro Asp Arg Lys Met Leu Pro Cys Tyr Ser Thr Ala Arg Ile Pro Leu 85 90 95 Pro Asn Leu Asn Glu Asp Leu Thr Cys Gly Asn Leu Leu Met Trp Glu 100 105 110 Ala Val Thr Val Lys Thr Glu Val Met Gly Ile Thr Ser Met Leu Asn 115 120 125 Leu His Ala Gly Ser Gln Lys Val His Glu Asn Gly Gly Gly Lys Pro 130 135 140 Ile Gln Gly Ser Asn Phe His Phe Phe Ala Val Gly Gly Asp Pro Leu 145 150 155 160 Glu Met Gln Gly Val Leu Met Asn Tyr Arg Thr Lys Tyr Pro Glu Gly 165 170 175 Thr Val Thr Pro Lys Asn Pro Thr Ala Gln Ser Gln Val Met Asn Thr 180 185 190 Asp His Lys Ala Tyr Leu Asp Lys Asn Asn Ala Tyr Pro Val Glu Cys 195 200 205 Trp Ile Pro Asp Pro Ser Arg Asn Glu Asn Thr Arg Tyr Phe Gly Thr 210 215 220 Tyr Thr Gly Gly Glu Asn Val Pro Pro Val Leu His Val Thr Asn Thr 225 230 235 240 Ala Thr Thr Val Leu Leu Asp Glu Gln Gly Val Gly Pro Leu Cys Lys 245 250 255 Ala Asp Ser Leu Tyr Val Ser Ala Ala Asp Ile Cys Gly Leu Phe Ile 260 265 270 Asn Ser Ser Gly Thr Gln Gln Trp Arg Gly Leu Pro Arg Tyr Phe Lys 275 280 285 Ile Arg Leu Arg Lys Arg Ser Val Lys Asn Pro Tyr Pro Ile Ser Phe 290 295 300 Leu Leu Ser Asp Leu Ile Asn Arg Arg Thr Gln Arg Val Asp Gly Gln 305 310 315 320 Pro Met Tyr Gly Met Glu Ser Gln Val Glu Glu Val Arg Val Phe Asp 325 330 335 Gly Thr Glu Gln Leu Pro Gly Asp Pro Asp Met Ile Arg Tyr Ile Asp 340 345 350 Arg Gln Gly Gln Leu Gln Thr Lys Met Val 355 360 115362PRTBK virus 115Met Ala Pro Thr Lys Arg Lys Gly Glu Cys Pro Gly Ala Ala Pro Lys 1 5 10 15 Lys Pro Lys Glu Pro Val Gln Val Pro Lys Leu Leu Ile Lys Gly Gly 20 25 30 Val Glu Val Leu Glu Val Lys Thr Gly Val Asp Ala Ile Thr Glu Val 35 40 45 Glu Cys Phe Leu Asn Pro Glu Met Gly Asp Pro Asp Asn Asp Leu Arg 50 55 60 Gly Tyr Ser Leu Arg Leu Thr Ala Glu Thr Ala Phe Asp Ser Asp Ser 65 70 75 80 Pro Asp Arg Lys Met Leu Pro Cys Tyr Ser Thr Ala Arg Ile Pro Leu 85 90 95 Pro Asn Leu Asn Glu Asp Leu Thr Cys Gly Asn Leu Leu Met Trp Glu 100 105 110 Ala Val Thr Val Lys Thr Glu Val Ile Gly Ile Thr Ser Met Leu Asn 115 120 125 Leu His Ala Gly Ser Gln Lys Val His Gln Asn Gly Gly Gly Lys Pro 130 135 140 Val Gln Gly Ser Asn Phe His Phe Phe Ala Val Gly Gly Asp Pro Leu 145 150 155 160 Glu Met Gln Gly Val Leu Met Asn Tyr Arg Thr Lys Tyr Pro Glu Gly 165 170 175 Thr Val Thr Pro Lys Asn Pro Thr Ala Gln Ser Gln Val Met Asn Thr 180 185 190 Asp His Lys Ala Tyr Leu Asp Lys Asn Asn Ala Tyr Pro Val Glu Cys 195 200 205 Trp Ile Pro Asp Pro Ser Arg Asn Glu Asn Thr Arg Tyr Phe Gly Thr 210 215 220 Tyr Thr Gly Gly Glu Asn Val Pro Pro Val Leu His Val Thr Asn Thr 225 230 235 240 Ala Thr Thr Val Leu Leu Asp Glu Gln Gly Val Gly Pro Leu Cys Lys 245 250 255 Ala Asp Ser Leu Tyr Val Ser Ala Ala Asp Ile Cys Gly Leu Phe Thr 260 265 270 Asn Ser Ser Gly Thr Gln Gln Trp Arg Gly Leu Pro Arg Tyr Phe Lys 275 280 285 Ile Arg Leu Arg Lys Arg Ser Val Lys Asn Pro Tyr Pro Ile Ser Phe 290 295 300 Leu Leu Ser Asp Leu Ile Asn Arg Arg Thr Gln Arg Val Asp Gly Gln 305 310 315 320 Pro Met Tyr Gly Met Glu Ser Gln Val Glu Glu Val Arg Val Phe Asp 325 330 335 Gly Thr Glu Gln Leu Pro Gly Asp Pro Asp Met Ile Arg Tyr Ile Asp 340 345 350 Arg Gln Gly Gln Leu Gln Thr Lys Met Val 355 360 116362PRTBK virus 116Met Ala Pro Thr Lys Arg Lys Gly Glu Cys Pro Gly Ala Ala Pro Lys 1 5 10 15 Lys Pro Lys Asp Pro Val Gln Val Pro Lys Leu Leu Ile Lys Gly Gly 20 25 30 Val Glu Val Leu Glu Val Lys Thr Gly Val Asp Ala Ile Thr Glu Val 35 40 45 Glu Cys Phe Leu Asn Pro Glu Met Gly Asp Pro Asp Asn Asp Leu Arg 50 55 60 Gly Tyr Ser Leu Arg Leu Thr Ala Glu Thr Ala Phe Asp Ser Asp Ser 65 70 75 80 Pro Asp Arg Lys Met Leu Pro Cys Tyr Ser Thr Ala Arg Ile Pro Leu 85 90 95 Pro Asn Leu Asn Glu Asp Leu Thr Cys Gly Asn Leu Leu Met Trp Glu 100 105 110 Ala Val Thr Val Lys Thr Glu Val Ile Gly Ile Thr Ser Met Leu Asn 115 120 125 Leu His Ala Gly Ser Gln Lys Val His Glu Asn Gly Gly Gly Lys Pro 130 135 140 Ile Gln Gly Ser Asn Phe His Phe Phe Ala Val Gly Gly Asp Pro Leu 145 150 155 160 Glu Met Gln Gly Val Leu Met Asn Tyr Arg Thr Lys Tyr Pro Glu Gly 165 170 175 Thr Val Thr Pro Lys Asn Pro Thr Ala Gln Ser Gln Val Met Asn Thr 180 185 190 Asp His Lys Ala Tyr Leu Asp Lys Asn Asn Ala Tyr Pro Val Glu Cys 195 200 205 Trp Ile Pro Asp Pro Ser Arg Asn Glu Asn Thr Arg Tyr Phe Gly Thr 210 215 220 Tyr Thr Gly Gly Glu Asn Val Pro Pro Val Leu His Val Thr Asn Thr 225 230 235 240 Ala Thr Thr Val Leu Leu Asp Glu Gln Gly Val Gly Pro Leu Cys Lys 245 250 255 Ala Asp Ser Leu Tyr Val Ser Ala Ala Asp Ile Cys Gly Leu Phe Thr 260 265 270 Asn Ser Ser Gly Thr Gln Gln Trp Arg Gly Leu Pro Arg Tyr Phe Lys 275 280 285 Ile Arg Leu Arg Lys Arg Ser Val Lys Asn Pro Tyr Pro Ile Ser Phe 290 295 300 Leu Leu Ser Asp Leu Ile Asn Arg Arg Thr Gln Arg Val Asp Gly Gln 305 310 315 320 Pro Met Tyr Gly Met Glu Ser Gln Val Glu Glu Val Arg Val Phe Asp 325 330 335 Gly Thr Glu Gln Leu Pro Gly Asp Pro Asp Met Ile Arg Tyr Ile Asp 340 345 350 Arg Gln Gly Gln Leu Gln Thr Lys Met Val 355 360 117362PRTBK virus 117Met Ala Pro Thr Lys Arg Lys Gly Glu Cys Pro Gly Ala Ala Pro Lys 1 5 10 15 Lys Pro Lys Asp Pro Val Gln Val Pro Lys Leu Leu Ile Lys Gly Gly 20 25 30 Val Glu Val Leu Glu Val Lys Thr Gly Val Asp Ala Ile Thr Glu Val 35 40 45 Glu Cys Phe Leu Asn Pro Glu Met Gly Asp Pro Asp Asn Asp Leu Arg 50 55 60 Gly Tyr Ser Leu Arg Leu Thr Ala Glu Thr Ala Phe Asp Ser Asp Ser 65 70 75 80 Pro Asp Arg Lys Met Leu Pro Cys Tyr Ser Thr Ala Arg Ile Pro Leu 85 90 95 Pro Asn Leu Asn Glu Asp Leu Thr Cys Gly Asn Leu Leu Met Trp Glu 100 105 110 Ala Val Thr Val Lys Thr Glu Val Ile Gly Ile Thr Ser Met Leu Asn 115 120 125 Leu His Ala Gly Ser Gln Lys Val His Glu Asn Gly Gly Gly Lys Pro 130 135 140 Val Gln Gly Ser Asn Phe His Phe Phe Ala Val Gly Gly Asp Pro Leu 145 150 155 160 Glu Met Gln Gly Val Leu Met Asn Tyr Arg Thr Lys Tyr Pro Glu Gly 165 170 175 Thr Val Thr Pro Lys Asn Pro Thr Ala Gln Ser Gln Val Met Asn Thr 180 185 190 Asp His Lys Ala Tyr Leu Asp Lys Asn Asn Ala Tyr Pro Val Glu Cys 195 200 205 Trp Ile Pro Asp Pro Ser Arg Asn Glu Asn Thr Arg Tyr Phe Gly Thr 210 215 220 Tyr Thr Gly Gly Glu Asn Val Pro Pro Val Leu His Val Thr Asn Thr 225 230 235 240 Ala Thr Thr Val Leu Leu Asp Glu Gln Gly Val Gly Pro Leu Cys Lys 245 250 255 Ala Asp Ser Leu Tyr Val Ser Ala Ala Asp Ile Cys Gly Leu Phe Thr 260 265 270 Asn Ser Ser Gly Thr Gln Gln Trp Arg Gly Leu Pro Arg Tyr Phe Lys 275 280 285 Ile Arg Leu Arg Lys Arg Ser Val Lys Asn Pro Tyr Pro Ile Ser Phe 290 295 300 Leu Leu Ser Asp Leu Ile Asn Arg Arg Thr Gln Arg Val Asp Gly Gln 305 310 315 320 Pro Met Tyr Gly Met Glu Ser Gln Val Glu Glu Val Arg Val Phe Asp 325 330 335 Gly Thr Glu Gln Leu Pro Gly Asp Pro Asp Met Ile Arg Tyr Ile Asp 340 345 350 Arg Gln Gly Gln Leu Gln Thr Lys Met Val 355 360 118362PRTBK virus 118Met Ala Pro Thr Lys Arg Lys Gly Glu Cys Pro Gly Ala Ala Pro Lys 1 5 10 15 Lys Pro Lys Glu Pro Val Gln Val Pro Lys Leu Leu Ile Lys Gly Gly 20 25 30 Val Glu Val Leu Glu Val Lys Thr Gly Val Asp Ala Ile Thr Glu Val 35 40 45 Glu Cys Phe Leu Asn Pro Glu Met Gly Asp Pro Asp Ser Asp Leu Arg 50 55 60 Gly Tyr Ser Leu Arg Leu Thr Ala Glu Thr Ala Phe Asp Ser Asp Ser 65 70 75 80 Pro Asp Arg Lys Met Leu Pro Cys Tyr Ser Thr Ala Arg Ile Pro Leu 85 90 95 Pro Asn Leu Asn Glu Asp Leu Thr Cys Gly Asn Leu Leu Met Trp Glu 100 105 110 Ala Val Thr Val Lys Thr Glu Val Ile Gly Ile Thr Ser Met Leu Asn 115 120 125 Leu His Ala Gly Ser Gln Lys Val His Glu Asn Gly Gly Gly Lys Pro 130 135 140 Val Gln Gly Ser Asn Phe His Phe Phe Ala Val Gly Gly Asp Pro Leu 145 150 155 160 Glu Met Gln Gly Val Leu Met Asn Tyr Arg Thr Lys Tyr Pro Glu Gly 165 170 175 Thr Val Thr Pro Lys Asn Pro Thr Ala Gln Ser Gln Val Met Asn Thr 180 185 190 Asp His Lys Ala Tyr Leu Asp Lys Asn Asn Ala Tyr Pro Val Glu Cys 195 200 205 Trp Ile Pro Asp Pro Ser Arg Asn Glu Asn Thr Arg Tyr Phe Gly Thr 210 215 220 Tyr Thr Gly Gly Glu Asn Val Pro Pro Val Leu His Val Thr Asn Thr 225 230 235 240 Ala Thr Thr Val Leu Leu Asp Glu Gln Gly Val Gly Pro Leu Cys Lys 245 250 255 Ala Asp Ser Leu Tyr Val Ser Ala Ala Asp Ile Cys Gly Leu Phe Thr 260 265 270 Asn Ser Ser Gly Thr Gln Gln Trp Arg Gly Leu Pro Arg Tyr Phe Lys 275 280 285 Ile Arg Leu Arg Lys Arg Ser Val Lys Asn Pro Tyr Pro Ile Ser Phe 290 295 300 Leu Leu Ser Asp Leu Ile Asn Arg Arg Thr Gln Arg Val Asp Gly Gln 305 310 315 320 Pro Met Tyr Gly Met Glu Ser Gln Val Glu Glu Val Arg Val Phe Asp 325 330 335 Gly Thr Glu Gln Leu Pro Gly Asp Pro Asp Met Ile Arg Tyr Ile Asp 340 345 350 Arg Gln Gly Gln Leu Gln Thr Lys Met Val 355 360 119362PRTBK virus 119Met Ala Pro Thr Lys Arg Lys Gly Glu Cys Pro Gly Ala Ala Pro Lys 1 5 10 15 Lys Pro Lys Glu Pro Val Gln Val Pro Lys Leu Leu Ile Lys Gly Gly 20 25 30 Val Glu Val Leu Glu Val Lys Thr Gly Val Asp Ala Ile Thr Glu Val 35 40 45 Glu Cys Phe Leu Asn Pro Glu Met Gly Asp Pro Asp Asn Asp Leu Arg 50 55 60 Gly Tyr Ser Leu Arg Leu Thr Ala Glu Thr Ala Phe Asp Ser Asp Ser 65 70 75 80 Pro Asp Arg Lys Met Leu Pro Cys Tyr Ser Thr Ala Arg Ile Pro Leu 85 90 95 Pro Asn Leu Asn Glu Asp Leu Thr Cys Gly Asn Leu Leu Met Trp Glu 100 105 110 Ala Val Thr Val Lys Thr Glu Val Ile Gly Ile Thr Ser Met Leu Asn 115 120 125 Leu His Ala Gly Ser Gln Lys Val His Glu Asn Gly Gly Gly Lys Pro 130 135 140 Val Gln Gly Ser Asn Phe His Phe Phe Ala Val Gly Gly Asp Pro Leu 145 150 155 160 Glu Met Gln Gly Val Leu Met Asn Tyr Arg Thr Lys Tyr Pro Glu Gly 165 170 175 Thr Val Thr Pro Lys Asn Pro Thr Ala Gln Ser Gln Val Met Asn Thr 180 185 190 Asp His Lys Ala Tyr Leu Asp Lys Asn Asn Ala Tyr Pro Val Glu Cys 195 200 205 Trp Ile Pro Asp Pro Ser Arg Asn Glu Asn Thr Arg Tyr Phe Gly Thr 210 215 220 Tyr Thr Gly Gly Glu Asn Val Pro Pro Val Leu His Val Thr Asn Thr 225 230 235 240 Ala Thr Thr Val Leu Leu Asp Glu Gln Gly Val Gly Pro Leu Cys Lys 245 250 255 Ala Asp Ser Leu Tyr Val Ser Ala Ala Asp Ile Cys Gly Leu Phe Thr 260 265 270 Asn Ser Ser Gly Thr Gln Gln Trp Arg Gly Leu Pro Arg Tyr Phe Lys 275 280 285 Ile Arg Leu Arg Lys Arg Ser Val Lys Asn Pro Tyr Pro Ile Ser Phe 290 295 300 Leu Leu Ser Asp Leu Ile Asn Arg Arg Thr Gln Arg Val Asp Gly Gln 305 310 315 320 Pro Met Tyr Gly Met Glu Ser Gln Val Glu Glu Val Arg Val Phe Asp 325 330 335 Gly Thr Glu Gln Leu Pro Gly Asp Pro Asp Met Ile Arg Tyr Ile Asp 340 345 350 Arg Gln Gly Gln Leu Gln Thr Lys Met Val 355 360 120362PRTBK virus 120Met Ala Pro Thr Lys Arg Lys Gly Glu Cys Pro Gly Ala Ala Pro Lys 1 5 10 15 Lys Pro Lys Glu Pro Val Gln Val Pro Lys Leu Leu Ile Lys Gly Gly 20 25 30 Val Glu Val Leu Glu Val Lys Thr Gly Val Asp Ala Ile Thr Glu Val 35 40 45 Glu Cys Phe Leu Asn Pro Glu Met Gly Asp Pro Asp Asn Asp Leu Arg 50 55 60 Gly Tyr Ser Leu Arg Leu Thr Ala Glu Thr Ala Phe Glu Ser Asp Ser 65 70 75 80 Pro Asp Arg Lys Met Leu Pro Cys Tyr Ser Thr Ala Arg Ile Pro Leu 85 90 95 Pro Asn Leu Asn Glu Asp Leu Thr Cys Gly Asn Leu Leu Met Trp Glu 100 105 110 Ala Val Thr Val Lys Thr Glu Val Ile Gly Ile Thr Ser Met Leu Asn 115

120 125 Leu His Ala Gly Ser Gln Lys Val His Glu Asn Gly Gly Gly Lys Pro 130 135 140 Ile Gln Gly Ser Asn Phe His Phe Phe Ala Val Gly Gly Asp Pro Leu 145 150 155 160 Glu Met Gln Gly Val Leu Met Asn Tyr Arg Thr Lys Tyr Pro Glu Gly 165 170 175 Thr Val Thr Pro Lys Asn Pro Thr Ala Gln Ser Gln Val Met Asn Thr 180 185 190 Asp His Lys Ala Tyr Leu Asp Lys Asn Asn Ala Tyr Pro Val Glu Cys 195 200 205 Trp Ile Pro Asp Pro Ser Arg Asn Glu Asn Thr Arg Tyr Phe Gly Thr 210 215 220 Tyr Thr Gly Gly Glu Asn Val Pro Pro Val Leu His Val Thr Asn Thr 225 230 235 240 Ala Thr Thr Val Leu Leu Asp Glu Gln Gly Val Gly Pro Leu Cys Lys 245 250 255 Ala Asp Ser Leu Tyr Val Ser Ala Ala Asp Ile Cys Gly Leu Phe Thr 260 265 270 Asn Ser Ser Gly Thr Gln Gln Trp Arg Gly Leu Pro Arg Tyr Phe Lys 275 280 285 Ile Arg Leu Arg Lys Arg Ser Val Lys Asn Pro Tyr Pro Ile Ser Phe 290 295 300 Leu Leu Ser Asp Leu Ile Asn Arg Arg Thr Gln Arg Val Asp Gly Gln 305 310 315 320 Pro Met Tyr Gly Met Glu Ser Gln Val Glu Glu Val Arg Val Phe Asp 325 330 335 Gly Thr Glu Gln Leu Pro Gly Asp Pro Asp Met Ile Arg Tyr Ile Asp 340 345 350 Arg Gln Gly Gln Leu Gln Thr Lys Met Val 355 360 121362PRTBK virus 121Met Ala Pro Thr Lys Arg Lys Gly Glu Cys Pro Gly Ala Ala Pro Lys 1 5 10 15 Lys Pro Lys Glu Pro Val Gln Val Pro Lys Leu Leu Ile Lys Gly Gly 20 25 30 Val Glu Val Leu Glu Val Lys Thr Gly Val Asp Ala Ile Thr Glu Val 35 40 45 Glu Cys Phe Leu Asn Pro Glu Met Gly Asp Pro Asp Asn Asp Leu Arg 50 55 60 Gly Tyr Ser Leu Arg Leu Thr Ala Glu Thr Ala Phe Lys Ser Asp Ser 65 70 75 80 Pro Asp Arg Lys Met Leu Pro Cys Tyr Ser Thr Ala Arg Ile Pro Leu 85 90 95 Pro Asn Leu Asn Glu Asp Leu Thr Cys Gly Asn Leu Leu Met Trp Glu 100 105 110 Ala Val Thr Val Lys Thr Glu Val Ile Gly Ile Thr Ser Met Leu Asn 115 120 125 Leu His Ala Gly Ser Gln Lys Val His Glu Asn Gly Gly Gly Lys Pro 130 135 140 Ile Gln Gly Ser Asn Phe His Phe Phe Ala Val Gly Gly Asp Pro Leu 145 150 155 160 Glu Met Gln Gly Val Leu Met Asn Tyr Arg Thr Lys Tyr Pro Glu Gly 165 170 175 Thr Val Thr Pro Lys Asn Pro Thr Ala Gln Ser Gln Val Met Asn Thr 180 185 190 Asp His Lys Ala Tyr Leu Asp Lys Asn Asn Ala Tyr Pro Val Glu Cys 195 200 205 Trp Ile Pro Asp Pro Ser Arg Asn Glu Asn Thr Arg Tyr Phe Gly Thr 210 215 220 Tyr Thr Gly Gly Glu Asn Val Pro Pro Val Leu His Val Thr Asn Thr 225 230 235 240 Ala Thr Thr Val Leu Leu Asp Glu Gln Gly Val Gly Pro Leu Cys Lys 245 250 255 Ala Asp Ser Leu Tyr Val Ser Ala Ala Asp Ile Cys Gly Leu Phe Thr 260 265 270 Asn Ser Ser Gly Thr Gln Gln Trp Arg Gly Leu Pro Arg Tyr Phe Lys 275 280 285 Ile Arg Leu Arg Lys Arg Ser Val Lys Asn Pro Tyr Pro Ile Ser Phe 290 295 300 Leu Leu Ser Asp Leu Ile Asn Arg Arg Thr Gln Arg Val Asp Gly Gln 305 310 315 320 Pro Met Tyr Gly Met Glu Ser Gln Val Glu Glu Val Arg Val Phe Asp 325 330 335 Gly Thr Glu Gln Leu Pro Gly Asp Pro Asp Met Ile Arg Tyr Ile Asp 340 345 350 Arg Gln Gly Gln Leu Gln Thr Lys Met Val 355 360 122362PRTBK virus 122Met Ala Pro Thr Lys Arg Lys Gly Glu Cys Pro Gly Ala Ala Pro Lys 1 5 10 15 Lys Pro Lys Glu Pro Val Gln Val Pro Lys Leu Leu Ile Lys Gly Gly 20 25 30 Val Glu Val Leu Glu Val Lys Thr Gly Val Asp Ala Ile Thr Glu Val 35 40 45 Glu Cys Phe Leu Asn Pro Glu Met Gly Asp Pro Asp Asn Asp Leu Arg 50 55 60 Gly Tyr Ser Leu Arg Leu Thr Ala Glu Thr Ala Phe Asp Ser Asp Ser 65 70 75 80 Pro Asp Arg Lys Met Leu Pro Cys Tyr Ser Thr Ala Arg Ile Pro Leu 85 90 95 Pro Asn Leu Asn Glu Asp Leu Thr Cys Gly Asn Leu Leu Met Trp Glu 100 105 110 Ala Val Thr Val Lys Thr Glu Val Ile Gly Ile Thr Ser Met Leu Asn 115 120 125 Leu His Ala Gly Ser Gln Lys Val His Glu Asn Gly Gly Gly Lys Pro 130 135 140 Ile Gln Gly Ser Asn Phe His Phe Phe Ala Val Gly Gly Asp Pro Leu 145 150 155 160 Glu Met Gln Gly Val Leu Met Asn Tyr Arg Thr Lys Tyr Pro Glu Gly 165 170 175 Thr Val Thr Pro Lys Asn Pro Thr Ala Gln Ser Gln Val Met Asn Thr 180 185 190 Asp His Lys Ala Tyr Leu Asp Lys Asn Asn Ala Tyr Pro Val Glu Cys 195 200 205 Trp Ile Pro Asp Pro Ser Arg Asn Glu Asn Thr Arg Tyr Phe Gly Thr 210 215 220 Tyr Thr Gly Gly Glu Asn Val Pro Pro Val Leu His Val Thr Asn Thr 225 230 235 240 Ala Thr Thr Val Leu Leu Asp Glu Gln Gly Val Gly Pro Leu Cys Lys 245 250 255 Ala Asp Ser Leu Tyr Val Ser Ala Ala Asp Ile Cys Gly Leu Phe Thr 260 265 270 Asn Ser Ser Gly Thr Gln Gln Trp Arg Gly Leu Pro Arg Tyr Phe Lys 275 280 285 Ile Arg Met Arg Lys Arg Ser Val Lys Asn Pro Tyr Pro Ile Ser Phe 290 295 300 Phe Ile Ser Asp Leu Ile Asn Arg Arg Thr Gln Arg Val Asp Gly Gln 305 310 315 320 Pro Met Tyr Gly Met Glu Ser Gln Val Glu Glu Val Arg Val Phe Asp 325 330 335 Gly Thr Glu Gln Leu Pro Gly Met Pro Asp Leu Ile Arg Tyr Ile Asp 340 345 350 Arg Gln Gly Gln Leu Gln Thr Lys Met Val 355 360 123362PRTBK virusmisc_feature(186)..(186)Xaa can be any naturally occurring amino acid 123Met Ala Pro Thr Lys Arg Lys Gly Glu Cys Pro Gly Ala Ala Pro Lys 1 5 10 15 Lys Pro Lys Glu Pro Val Gln Val Pro Lys Leu Leu Ile Lys Gly Gly 20 25 30 Val Glu Val Leu Glu Val Lys Thr Gly Val Asp Ala Ile Thr Glu Val 35 40 45 Glu Cys Phe Leu Asn Pro Glu Met Gly Asp Pro Asp Asn Asp Leu Arg 50 55 60 Gly Tyr Ser Leu Arg Leu Thr Ala Glu Thr Ala Phe Asn Ser Asp Ser 65 70 75 80 Pro Asp Arg Lys Met Leu Pro Cys Tyr Ser Thr Ala Arg Ile Pro Leu 85 90 95 Pro Asn Leu Asn Glu Asp Leu Thr Cys Gly Asn Leu Leu Met Trp Glu 100 105 110 Ala Val Thr Val Lys Thr Glu Val Ile Gly Ile Thr Ser Met Leu Asn 115 120 125 Leu His Ala Gly Ser Gln Lys Val His Glu Asn Gly Gly Gly Lys Pro 130 135 140 Ile Gln Gly Ser Asn Phe His Phe Phe Ala Val Gly Gly Asp Pro Leu 145 150 155 160 Glu Met Gln Gly Val Leu Met Asn Tyr Arg Thr Lys Tyr Pro Glu Gly 165 170 175 Thr Val Thr Pro Lys Asn Pro Thr Ala Xaa Ser Gln Val Met Asn Thr 180 185 190 Asp His Lys Ala Tyr Leu Asp Lys Asn Asn Ala Tyr Pro Val Glu Cys 195 200 205 Trp Ile Pro Asp Pro Ser Arg Asn Glu Asn Thr Arg Tyr Phe Gly Thr 210 215 220 Tyr Thr Gly Gly Glu Asn Val Pro Pro Val Leu His Val Thr Asn Thr 225 230 235 240 Ala Thr Thr Val Leu Leu Asp Glu Gln Gly Val Gly Pro Leu Cys Lys 245 250 255 Ala Asp Ser Leu Tyr Val Ser Ala Ala Asp Ile Cys Gly Leu Phe Thr 260 265 270 Asn Ser Ser Gly Thr Gln Gln Trp Arg Gly Leu Pro Arg Tyr Phe Lys 275 280 285 Ile Arg Leu Arg Lys Arg Ser Val Lys Asn Pro Tyr Pro Ile Ser Phe 290 295 300 Leu Leu Ser Asp Leu Ile Asn Arg Arg Thr Gln Arg Val Asp Gly Gln 305 310 315 320 Pro Met Tyr Gly Met Glu Ser Gln Val Glu Glu Val Arg Val Phe Asp 325 330 335 Gly Thr Glu Gln Leu Pro Gly Asp Pro Asp Met Ile Arg Tyr Ile Asp 340 345 350 Arg Gln Gly Gln Leu Gln Thr Lys Met Val 355 360 124362PRTBK virus 124Met Ala Pro Thr Lys Arg Lys Gly Glu Cys Pro Gly Ala Ala Pro Lys 1 5 10 15 Lys Pro Lys Glu Pro Val Gln Val Pro Lys Leu Leu Ile Lys Gly Gly 20 25 30 Val Glu Val Leu Glu Val Lys Thr Gly Val Asp Ala Ile Thr Glu Val 35 40 45 Glu Cys Phe Leu Asn Pro Glu Met Gly Asp Pro Asp Asn Asp Leu Arg 50 55 60 Gly Tyr Ser Leu Arg Leu Thr Ala Glu Thr Ala Phe Asp Ser Asp Ser 65 70 75 80 Pro Asp Arg Lys Met Leu Pro Cys Tyr Ser Thr Ala Arg Ile Pro Leu 85 90 95 Pro Asn Leu Asn Glu Asp Leu Thr Cys Gly Asn Leu Leu Met Trp Glu 100 105 110 Ala Val Thr Val Lys Thr Glu Val Ile Gly Ile Thr Ser Met Leu Asn 115 120 125 Leu His Ala Gly Ser Gln Lys Val His Glu Asn Gly Gly Gly Lys Pro 130 135 140 Ile Gln Gly Ser Asn Phe His Phe Phe Ala Val Gly Gly Asp Pro Leu 145 150 155 160 Glu Met Gln Gly Val Leu Met Asn Tyr Arg Thr Lys Tyr Pro Glu Gly 165 170 175 Thr Val Thr Pro Lys Asn Pro Thr Ala Gln Ser Gln Val Met Asn Thr 180 185 190 Asp His Lys Ala Tyr Leu Asp Lys Asn Asn Ala Tyr Pro Val Glu Cys 195 200 205 Trp Ile Pro Asp Pro Ser Lys Asn Glu Asn Thr Arg Tyr Phe Gly Thr 210 215 220 Tyr Thr Gly Gly Glu Asn Val Pro Pro Val Leu His Val Thr Asn Thr 225 230 235 240 Ala Thr Thr Val Leu Leu Asp Glu Gln Gly Val Gly Pro Leu Cys Lys 245 250 255 Ala Asp Ser Leu Tyr Val Ser Ala Ala Asp Ile Cys Gly Leu Phe Thr 260 265 270 Asn Ser Ser Gly Thr Gln Gln Trp Arg Gly Leu Pro Arg Tyr Phe Lys 275 280 285 Ile Arg Leu Arg Lys Arg Ser Val Lys Asn Pro Tyr Pro Ile Ser Phe 290 295 300 Leu Leu Ser Asp Leu Ile Asn Arg Arg Thr Gln Arg Val Asp Gly Gln 305 310 315 320 Pro Met Tyr Gly Met Glu Ser Gln Val Glu Glu Val Arg Val Phe Asp 325 330 335 Gly Thr Glu Gln Leu Pro Gly Asp Pro Asp Met Ile Arg Tyr Ile Asp 340 345 350 Arg Gln Gly Gln Leu Gln Thr Lys Met Val 355 360 125362PRTBK virus 125Met Ala Pro Thr Lys Arg Lys Gly Glu Cys Pro Gly Ala Ala Pro Lys 1 5 10 15 Lys Pro Lys Glu Pro Val Gln Val Pro Lys Leu Leu Ile Lys Gly Gly 20 25 30 Val Glu Val Leu Glu Val Lys Thr Gly Val Asp Ala Ile Thr Glu Val 35 40 45 Glu Cys Phe Leu Asn Pro Glu Met Gly Asp Pro Asp Asn Asp Leu Arg 50 55 60 Gly Tyr Ser Leu Arg Leu Thr Ala Glu Thr Ala Phe Asn Ser Asp Ser 65 70 75 80 Pro Asp Arg Lys Met Leu Pro Cys Tyr Ser Thr Ala Arg Ile Pro Leu 85 90 95 Pro Asn Leu Asn Glu Asp Leu Thr Cys Gly Asn Leu Leu Met Trp Glu 100 105 110 Ala Val Thr Val Lys Thr Glu Val Ile Gly Ile Thr Ser Met Leu Asn 115 120 125 Leu His Ala Gly Ser Gln Lys Val His Asp Asn Gly Gly Gly Lys Pro 130 135 140 Ile Gln Gly Ser Asn Phe His Phe Phe Ala Val Gly Gly Asp Pro Leu 145 150 155 160 Glu Met Gln Gly Val Leu Met Asn Tyr Arg Thr Lys Tyr Pro Glu Gly 165 170 175 Thr Val Thr Pro Lys Asn Pro Thr Ala Gln Ser Gln Val Met Asn Thr 180 185 190 Asp His Lys Ala Tyr Leu Asp Lys Asn Asn Ala Tyr Pro Val Glu Cys 195 200 205 Trp Ile Pro Asp Pro Ser Arg Asn Glu Asn Thr Arg Tyr Phe Gly Thr 210 215 220 Tyr Thr Gly Gly Glu Asn Val Pro Pro Val Leu His Val Thr Asn Thr 225 230 235 240 Ala Thr Thr Val Leu Leu Asp Glu Gln Gly Val Gly Pro Leu Cys Lys 245 250 255 Ala Asp Ser Leu Tyr Val Ser Ala Ala Asp Ile Cys Gly Leu Phe Thr 260 265 270 Asn Ser Ser Gly Thr Gln Gln Trp Arg Gly Leu Pro Arg Tyr Phe Lys 275 280 285 Ile Arg Leu Arg Lys Arg Ser Val Lys Asn Pro Tyr Pro Ile Ser Phe 290 295 300 Leu Leu Ser Asp Leu Ile Asn Arg Arg Thr Gln Arg Val Asp Gly Gln 305 310 315 320 Pro Met Tyr Gly Met Glu Ser Gln Val Glu Glu Val Arg Val Phe Asp 325 330 335 Gly Thr Glu Lys Leu Pro Gly Asp Pro Asp Met Ile Arg Tyr Ile Asp 340 345 350 Arg Gln Gly Gln Leu Gln Thr Lys Met Val 355 360 126144PRTBK virus 126Gly Gly Val Glu Val Leu Glu Val Lys Thr Gly Val Asp Ala Ile Thr 1 5 10 15 Glu Val Glu Cys Phe Leu Asn Pro Glu Met Gly Asp Pro Asp Asn Asp 20 25 30 Leu Arg Gly Tyr Ser Leu Arg Leu Thr Ala Glu Thr Ala Phe Glu Ser 35 40 45 Asp Ser Pro Asp Arg Lys Met Leu Pro Cys Tyr Ser Thr Ala Arg Ile 50 55 60 Pro Leu Pro Asn Leu Asn Glu Asp Leu Thr Cys Gly Asn Leu Leu Met 65 70 75 80 Trp Glu Ala Val Thr Val Lys Thr Glu Val Ile Gly Ile Thr Ser Met 85 90 95 Leu Asn Leu His Ala Gly Ser Gln Lys Val His Glu Asn Gly Gly Gly 100 105 110 Lys Pro Ile Gln Gly Ser Asn Phe His Phe Phe Ala Val Gly Gly Asp 115 120 125 Pro Leu Glu Met Gln Gly Val Leu Met Asn Tyr Arg Thr Lys Tyr Pro 130 135 140 127144PRTBK virus 127Gly Gly Val Glu Val Leu Glu Val Lys Thr Gly Leu Asp Ala Ile Thr 1 5 10 15 Glu Val Glu Cys Phe Leu Asn Pro Glu Met Gly Asp Pro Asp Glu Asn 20 25 30 Leu Arg Gly Phe Ser Leu Lys Leu Ser Ala Glu Asn Asp Phe Ser Ser 35 40 45 Asp Ser Pro Glu Arg Lys Met Leu Pro Cys Tyr Ser Thr Ala Arg Ile 50 55 60 Pro Leu Pro Asn Leu Asn Glu Asp Leu Thr Cys Gly Asn Leu Leu Met 65 70 75 80 Trp Glu Ala Val Thr Val Gln Thr Glu Val Ile

Gly Ile Thr Ser Met 85 90 95 Leu Asn Leu His Ala Gly Ser Gln Lys Val His Glu His Gly Gly Gly 100 105 110 Lys Pro Ile Gln Gly Ser Asn Phe His Phe Phe Ala Val Gly Gly Asp 115 120 125 Pro Leu Glu Met Gln Gly Val Leu Met Asn Tyr Arg Thr Lys Tyr Pro 130 135 140 128144PRTBK virus 128Gly Gly Val Glu Val Leu Glu Val Lys Thr Gly Val Asp Ala Ile Thr 1 5 10 15 Glu Val Glu Cys Phe Leu Asn Pro Glu Met Gly Asp Pro Asp Asn Asp 20 25 30 Leu Arg Gly Tyr Ser Leu Arg Leu Thr Ala Glu Thr Ala Phe Asp Ser 35 40 45 Asp Ser Pro Asp Arg Lys Met Leu Pro Cys Tyr Ser Thr Ala Arg Ile 50 55 60 Pro Leu Pro Asn Leu Asn Glu Asp Leu Thr Cys Gly Asn Leu Leu Met 65 70 75 80 Trp Glu Ala Val Thr Val Lys Thr Glu Val Ile Gly Ile Thr Ser Met 85 90 95 Leu Asn Leu His Ala Gly Ser Gln Lys Val His Glu Asn Gly Gly Gly 100 105 110 Lys Pro Ile Gln Gly Ser Asn Phe His Phe Phe Ala Val Gly Gly Asp 115 120 125 Pro Leu Glu Met Gln Gly Val Leu Met Asn Tyr Arg Thr Lys Tyr Pro 130 135 140 129144PRTBK virus 129Gly Gly Val Glu Val Leu Glu Val Lys Thr Gly Val Asp Ala Ile Thr 1 5 10 15 Glu Val Glu Cys Phe Leu Asn Pro Glu Met Gly Asp Pro Asp Asn Asp 20 25 30 Leu Arg Gly Tyr Ser Leu Arg Leu Thr Ala Glu Thr Ala Phe Glu Ser 35 40 45 Asp Ser Pro Asp Arg Lys Met Leu Pro Cys Tyr Ser Thr Ala Arg Ile 50 55 60 Pro Leu Pro Asn Leu Asn Glu Asp Leu Thr Cys Gly Asn Leu Leu Met 65 70 75 80 Trp Glu Ala Val Thr Val Lys Thr Glu Val Ile Gly Ile Thr Ser Met 85 90 95 Leu Asn Leu His Ala Gly Ser Gln Lys Val His Glu Asn Gly Gly Gly 100 105 110 Lys Pro Ile Gln Gly Ser Asn Phe His Phe Phe Ala Val Gly Gly Asp 115 120 125 Pro Leu Glu Met Gln Gly Val Leu Met Asn Tyr Arg Thr Ser Tyr Pro 130 135 140 130144PRTBK virus 130Gly Gly Val Glu Val Leu Glu Val Lys Thr Gly Val Asp Ala Ile Thr 1 5 10 15 Glu Val Glu Cys Phe Leu Asn Pro Glu Met Gly Asp Pro Asp Asn Asp 20 25 30 Leu Arg Gly Tyr Ser Leu Arg Leu Thr Ala Glu Thr Ala Phe Glu Ser 35 40 45 Asp Ser Pro Asp Arg Lys Met Leu Pro Cys Tyr Ser Thr Ala Arg Ile 50 55 60 Pro Leu Pro Asn Leu Asn Glu Asp Leu Thr Cys Gly Asn Leu Leu Met 65 70 75 80 Trp Glu Ala Val Thr Val Lys Thr Glu Val Ile Gly Ile Thr Ser Met 85 90 95 Leu Asn Leu His Ala Gly Ser Gln Lys Val His Glu Asn Gly Gly Gly 100 105 110 Lys Pro Ile Gln Gly Ser Asn Phe His Phe Phe Ala Val Gly Gly Asp 115 120 125 Pro Leu Glu Met Gln Gly Val Leu Met Asn Tyr Arg Thr Lys Tyr Pro 130 135 140 131144PRTBK virus 131Gly Gly Val Glu Val Leu Glu Val Lys Thr Gly Val Asp Ala Ile Thr 1 5 10 15 Glu Val Glu Cys Phe Leu Asn Pro Glu Met Gly Asp Pro Asp Asn Asp 20 25 30 Leu Arg Gly Tyr Ser Leu Arg Leu Thr Ala Glu Thr Ala Phe Glu Ser 35 40 45 Asp Ser Pro Asp Arg Lys Met Leu Pro Cys Tyr Ser Thr Ala Arg Ile 50 55 60 Pro Leu Pro Asn Leu Asn Glu Asp Leu Thr Cys Gly Asn Leu Leu Met 65 70 75 80 Trp Glu Ala Val Thr Val Lys Thr Glu Val Ile Gly Ile Thr Ser Met 85 90 95 Leu Asn Leu His Ala Gly Ser Gln Lys Val His Glu Asn Gly Gly Gly 100 105 110 Lys Pro Ile Gln Gly Ser Asn Phe His Phe Phe Ala Val Gly Gly Asp 115 120 125 Pro Leu Glu Met Gln Gly Val Leu Met Asn Tyr Arg Thr Lys Tyr Pro 130 135 140 132144PRTBK virus 132Gly Gly Val Glu Val Leu Glu Val Lys Thr Gly Val Asp Ala Ile Thr 1 5 10 15 Glu Val Glu Cys Phe Leu Asn Pro Glu Met Gly Asp Pro Asp Glu Asn 20 25 30 Leu Arg Gly Phe Ser Leu Lys Leu Ser Ala Glu Asn Asp Phe Ser Ser 35 40 45 Asp Ser Pro Glu Arg Lys Met Leu Pro Cys Tyr Ser Thr Ala Arg Ile 50 55 60 Pro Leu Pro Asn Leu Asn Glu Asp Leu Thr Cys Gly Asn Leu Leu Met 65 70 75 80 Trp Glu Ala Val Thr Val Gln Thr Glu Val Ile Gly Ile Thr Ser Met 85 90 95 Leu Asn Leu His Ala Gly Ser Gln Lys Val His Glu His Gly Gly Gly 100 105 110 Lys Pro Ile Gln Gly Ser Asn Phe His Phe Phe Ala Val Gly Gly Asp 115 120 125 Pro Leu Glu Met Gln Gly Val Leu Leu Asn Tyr Arg Thr Lys Tyr Pro 130 135 140 133144PRTBK virus 133Gly Gly Val Glu Val Leu Glu Val Lys Thr Gly Val Asp Ala Ile Thr 1 5 10 15 Glu Val Glu Cys Phe Leu Asn Pro Glu Met Gly Asp Pro Asp Ser Asp 20 25 30 Leu Arg Gly Tyr Arg Leu Arg Leu Thr Ala Glu Thr Ala Phe Glu Ser 35 40 45 Asp Ser Pro Asp Arg Lys Met Leu Pro Cys Tyr Ser Thr Ala Arg Ile 50 55 60 Pro Leu Pro Asn Leu Asn Glu Asp Leu Thr Cys Gly Asn Leu Leu Met 65 70 75 80 Trp Glu Ala Val Thr Val Lys Thr Glu Val Ile Gly Ile Thr Ser Met 85 90 95 Leu Asn Leu His Ala Gly Ser Gln Lys Val His Glu Asn Gly Gly Gly 100 105 110 Lys Pro Ile Gln Gly Ser Asn Phe His Phe Phe Ala Val Gly Gly Asp 115 120 125 Pro Leu Glu Met Gln Gly Val Leu Met Asn Tyr Arg Thr Lys Tyr Pro 130 135 140 134144PRTBK virus 134Gly Gly Val Glu Val Leu Glu Val Lys Thr Gly Val Asp Ala Ile Thr 1 5 10 15 Glu Val Glu Cys Phe Leu Asn Pro Glu Met Gly Asp Pro Asp Asn Asp 20 25 30 Leu Trp Gly Tyr Ser Leu Arg Leu Thr Ala Glu Thr Ala Phe Glu Ser 35 40 45 Asp Ser Pro Asp Arg Lys Met Leu Pro Cys Tyr Ser Thr Ala Arg Ile 50 55 60 Pro Leu Pro Asn Leu Asn Glu Asp Leu Thr Cys Gly Asn Leu Leu Met 65 70 75 80 Trp Glu Ala Val Thr Val Lys Thr Glu Val Ile Gly Ile Thr Ser Met 85 90 95 Leu Asn Leu His Ala Gly Ser Gln Lys Val His Glu Asn Gly Gly Gly 100 105 110 Lys Pro Ile Gln Gly Ser Asn Phe His Phe Phe Ala Val Gly Gly Asp 115 120 125 Pro Leu Glu Met Gln Gly Val Leu Met Asn Tyr Arg Thr Lys Tyr Pro 130 135 140 135144PRTBK virus 135Gly Gly Val Glu Val Leu Glu Val Lys Thr Gly Val Asp Ala Ile Thr 1 5 10 15 Glu Val Glu Cys Phe Leu Asn Pro Glu Met Gly Asp Pro Asp Asn Asp 20 25 30 Leu Arg Gly Tyr Ser Leu Arg Leu Thr Ala Glu Thr Ala Phe Glu Ser 35 40 45 Asp Ser Pro Asp Arg Lys Met Leu Pro Cys Tyr Ser Thr Ala Arg Ile 50 55 60 Pro Leu Pro Asn Leu Asn Glu Asp Leu Thr Cys Gly Asn Leu Leu Met 65 70 75 80 Trp Glu Ala Val Thr Val Lys Thr Glu Val Ile Gly Ile Thr Ser Met 85 90 95 Leu Asn Leu His Ala Gly Ser Gln Lys Val His Glu Asn Gly Gly Gly 100 105 110 Lys Pro Ile Gln Gly Ser Asn Phe His Phe Phe Ala Val Gly Gly Asp 115 120 125 Pro Leu Glu Met Gln Gly Val Leu Leu Asn Tyr Arg Thr Lys Tyr Pro 130 135 140 136144PRTBK virus 136Gly Gly Val Glu Val Leu Glu Val Lys Thr Gly Val Asp Ala Ile Thr 1 5 10 15 Glu Val Glu Cys Phe Leu Asn Pro Glu Met Gly Asp Pro Asp Glu Asn 20 25 30 Leu Arg Gly Phe Ser Leu Lys Leu Ser Ala Glu Asn Asp Phe Ser Ser 35 40 45 Asp Ser Pro Glu Arg Lys Met Leu Pro Cys Tyr Ser Thr Ala Arg Ile 50 55 60 Pro Leu Pro Asn Leu Asn Glu Asp Leu Thr Cys Gly Asn Leu Leu Met 65 70 75 80 Trp Glu Ala Val Thr Val Gln Thr Glu Val Ile Gly Ile Thr Ser Met 85 90 95 Leu Asn Leu His Ala Gly Ser Gln Lys Val His Glu His Gly Gly Gly 100 105 110 Lys Pro Ile Gln Gly Ser Asn Leu His Phe Phe Ala Val Gly Gly Asp 115 120 125 Pro Leu Glu Met Gln Gly Val Leu Leu Asn Tyr Arg Thr Lys Tyr Pro 130 135 140 137144PRTBK virus 137Gly Gly Val Glu Val Leu Glu Val Lys Thr Gly Val Asp Ala Ile Thr 1 5 10 15 Glu Val Glu Cys Phe Leu Asn Pro Glu Met Gly Asp Pro Asp Glu Asn 20 25 30 Leu Arg Gly Phe Ser Leu Lys Leu Ser Ala Glu Asn Asp Phe Ser Ser 35 40 45 Asp Ser Pro Glu Arg Lys Met Leu Pro Cys Tyr Ser Thr Ala Arg Ile 50 55 60 Pro Leu Pro Asn Leu Asn Glu Asp Leu Thr Cys Gly Asn Leu Leu Met 65 70 75 80 Trp Glu Ala Val Thr Val Gln Thr Glu Val Ile Gly Ile Thr Ser Met 85 90 95 Leu Asn Leu His Ala Gly Ser Gln Lys Val His Glu His Gly Gly Gly 100 105 110 Lys Pro Ile Gln Gly Ser Asn Phe His Phe Phe Ala Val Gly Gly Asp 115 120 125 Pro Leu Glu Met Gln Gly Val Leu Leu Asn Tyr Arg Thr Lys Tyr Pro 130 135 140 138144PRTBK virus 138Gly Gly Val Glu Val Leu Glu Val Lys Thr Gly Val Asp Ala Ile Thr 1 5 10 15 Glu Val Glu Cys Phe Leu Asn Pro Glu Met Gly Asp Pro Asp Glu Asn 20 25 30 Leu Arg Gly Phe Ser Leu Lys Leu Ser Ala Ala Asn Asp Phe Ser Ser 35 40 45 Asp Ser Pro Glu Arg Lys Met Leu Pro Cys Tyr Ser Thr Ala Arg Ile 50 55 60 Pro Leu Pro Asn Leu Asn Glu Asp Leu Thr Cys Gly Asn Leu Leu Met 65 70 75 80 Trp Glu Ala Val Thr Val Gln Thr Glu Val Ile Gly Ile Thr Ser Met 85 90 95 Leu Asn Leu His Ala Gly Ser Gln Lys Val His Glu His Gly Gly Gly 100 105 110 Lys Pro Ile Gln Gly Ser Asn Phe His Phe Phe Ala Val Gly Gly Asp 115 120 125 Pro Leu Glu Met Gln Gly Val Leu Leu Asn Tyr Arg Thr Lys Tyr Pro 130 135 140 139144PRTBK virus 139Gly Gly Val Glu Val Leu Glu Val Lys Thr Gly Val Asp Ala Ile Thr 1 5 10 15 Glu Val Glu Cys Phe Leu Asn Pro Glu Met Gly Asp Pro Asp Asn Asp 20 25 30 Leu Arg Gly Tyr Ser Leu Arg Leu Thr Ala Glu Thr Ala Phe Glu Ser 35 40 45 Asp Ser Pro Asp Arg Lys Met Leu Pro Cys Tyr Ser Thr Ala Arg Ile 50 55 60 Pro Leu Pro Asn Leu Asn Glu Asp Leu Thr Cys Gly Asn Leu Leu Met 65 70 75 80 Trp Glu Ala Val Thr Val Lys Thr Glu Val Ile Gly Ile Thr Ser Met 85 90 95 Leu Asn Leu His Ala Gly Ser Gln Lys Val His Glu Asn Gly Gly Gly 100 105 110 Lys Pro Ile Gln Gly Ser Asn Phe His Phe Phe Ala Val Gly Gly Asp 115 120 125 Pro Leu Glu Met Gln Gly Val Leu Met Asn Tyr Arg Thr Arg Tyr Pro 130 135 140 140144PRTBK virus 140Gly Gly Val Glu Val Leu Glu Val Lys Thr Gly Val Asp Ala Ile Thr 1 5 10 15 Glu Val Glu Cys Phe Leu Asn Pro Glu Met Gly Asp Pro Asp Asp Asn 20 25 30 Leu Arg Gly Tyr Ser Leu Lys Leu Thr Ala Glu Asn Ala Phe Asp Ser 35 40 45 Asp Ser Pro Asp Lys Lys Met Leu Pro Cys Tyr Ser Thr Ala Arg Ile 50 55 60 Pro Leu Pro Asn Leu Asn Glu Asp Leu Thr Cys Gly Asn Leu Leu Met 65 70 75 80 Trp Glu Ala Val Thr Val Lys Thr Glu Val Ile Gly Ile Thr Ser Met 85 90 95 Leu Asn Leu His Ala Gly Ser Gln Lys Val His Glu Asn Gly Gly Gly 100 105 110 Lys Pro Val Gln Gly Ser Asn Phe His Phe Phe Ala Val Gly Gly Asp 115 120 125 Pro Leu Glu Met Gln Gly Val Leu Met Asn Tyr Arg Thr Arg Tyr Pro 130 135 140 141144PRTBK virus 141Gly Gly Val Glu Val Leu Glu Val Lys Thr Gly Val Asp Ala Ile Thr 1 5 10 15 Glu Val Glu Cys Phe Leu Asn Pro Glu Met Gly Asp Pro Asp Glu Asn 20 25 30 Leu Arg Gly Phe Ser Leu Lys Leu Ser Ala Glu Asn Asp Phe Ser Ser 35 40 45 Asp Ser Pro Glu Arg Lys Met Leu Pro Cys Tyr Ser Thr Ala Arg Ile 50 55 60 Pro Leu Pro Asn Leu Asn Glu Asp Leu Thr Cys Gly Asn Leu Leu Met 65 70 75 80 Trp Glu Ala Val Thr Val Gln Thr Glu Val Ile Gly Ile Thr Ser Met 85 90 95 Leu Asn Leu His Ala Gly Ser Gln Lys Val His Glu His Gly Gly Gly 100 105 110 Lys Pro Ile Gln Gly Ser Asn Phe His Phe Phe Ala Val Gly Gly Asp 115 120 125 Pro Leu Glu Met Gln Gly Val Leu Leu Asn Tyr Arg Thr Lys Tyr Pro 130 135 140 142144PRTBK virus 142Gly Gly Val Glu Val Leu Glu Val Lys Thr Gly Val Asp Ala Ile Thr 1 5 10 15 Glu Val Glu Cys Phe Leu Asn Pro Glu Met Gly Asp Pro Asp Glu Asn 20 25 30 Leu Arg Gly Phe Ser Leu Lys Leu Ser Ala Glu Asn Asp Phe Ser Ser 35 40 45 Asp Ser Pro Glu Arg Lys Met Leu Pro Cys Tyr Ser Thr Ala Arg Ile 50 55 60 Pro Leu Pro Asn Leu Asn Glu Asp Leu Thr Cys Gly Asn Leu Leu Met 65 70 75 80 Trp Glu Ala Val Thr Val Gln Thr Glu Val Ile Gly Ile Thr Ser Met 85 90 95 Leu Asn Leu His Ala Gly Ser Gln Lys Val His Glu His Gly Gly Gly 100 105 110 Lys Pro Ile Gln Gly Ser Asn Phe His Phe Phe Ala Val Gly Gly Asp 115 120 125 Pro Leu Glu Met Gln Gly Val Leu Leu Asn Tyr Arg Thr Ser Tyr Pro 130 135 140 143144PRTBK virus 143Gly Gly Val Glu Val Leu Glu Val Lys Thr Gly Val Asp Ala Ile Thr 1 5 10 15 Glu Val Glu Cys Phe Leu Asn Pro Glu Met Gly Asp Pro Asp Asn Asp 20 25 30 Leu Arg Gly Tyr Ser Leu Arg Leu Thr Ala Glu Thr Ala Phe Asp

Ser 35 40 45 Asp Ser Pro Asp Arg Lys Met Leu Pro Cys Tyr Ser Thr Ala Arg Ile 50 55 60 Pro Leu Pro Asn Leu Asn Glu Asp Leu Thr Cys Gly Asn Leu Leu Met 65 70 75 80 Trp Glu Ala Val Thr Val Lys Thr Glu Val Ile Gly Ile Thr Ser Met 85 90 95 Leu Asn Leu His Ala Gly Ser Gln Lys Val His Glu Asn Gly Gly Gly 100 105 110 Lys Pro Ile Gln Gly Ser Asn Phe His Phe Phe Ala Val Gly Gly Asp 115 120 125 Pro Leu Glu Met Gln Gly Val Leu Met Asn Tyr Arg Thr Lys Tyr Pro 130 135 140 144144PRTBK virus 144Gly Gly Val Glu Val Leu Glu Val Lys Thr Gly Leu Asp Ala Ile Thr 1 5 10 15 Glu Val Glu Cys Phe Leu Asn Pro Glu Met Gly Asp Pro Asp Glu Asn 20 25 30 Leu Arg Gly Phe Ser Leu Lys Leu Ser Ala Glu Asn Asp Phe Ser Ser 35 40 45 Asp Ser Pro Glu Arg Lys Met Leu Pro Cys Tyr Ser Thr Ala Arg Ile 50 55 60 Pro Leu Pro Asn Leu Asn Glu Asp Leu Thr Cys Gly Asn Leu Leu Met 65 70 75 80 Trp Glu Ala Val Thr Val Gln Thr Glu Val Ile Gly Ile Thr Ser Met 85 90 95 Leu Asn Leu His Ala Gly Ser Gln Lys Val His Glu His Gly Gly Gly 100 105 110 Lys Pro Ile Gln Gly Ser Asn Phe His Phe Phe Ala Val Gly Gly Asp 115 120 125 Pro Leu Glu Met Gln Gly Val Leu Met Asn Tyr Arg Thr Arg Tyr Pro 130 135 140 145144PRTBK virus 145Gly Gly Val Glu Val Leu Glu Val Lys Thr Gly Val Asp Ala Ile Thr 1 5 10 15 Glu Val Glu Cys Phe Leu Asn Pro Glu Met Gly Asp Pro Asp Glu Asn 20 25 30 Leu Arg Gly Phe Ser Leu Lys Leu Ser Ala Glu Asn Asp Phe Ser Ser 35 40 45 Asp Ser Pro Glu Arg Lys Met Leu Pro Cys Tyr Ser Thr Ala Arg Ile 50 55 60 Pro Leu Pro Asn Leu Asn Glu Asp Leu Thr Cys Gly Asn Leu Leu Met 65 70 75 80 Trp Glu Ala Val Thr Val Gln Thr Glu Val Ile Gly Ile Thr Ser Met 85 90 95 Leu Asn Leu His Ala Gly Ser Gln Lys Val His Glu His Gly Gly Gly 100 105 110 Lys Pro Ile Gln Gly Ser Asn Phe His Phe Phe Ala Val Gly Gly Asp 115 120 125 Pro Leu Glu Met Gln Gly Val Leu Leu Asn Tyr Arg Thr Lys Tyr Pro 130 135 140 146144PRTBK virus 146Gly Gly Val Glu Val Leu Glu Val Lys Thr Gly Leu Asp Ala Ile Thr 1 5 10 15 Glu Val Glu Cys Phe Leu Asn Pro Glu Met Gly Asp Pro Asp Glu Asn 20 25 30 Leu Arg Gly Phe Ser Leu Lys Leu Ser Ala Glu Asn Asp Phe Ser Ser 35 40 45 Asp Ser Pro Glu Arg Lys Met Leu Pro Cys Tyr Ser Thr Ala Arg Ile 50 55 60 Pro Leu Pro Asn Leu Asn Glu Asp Leu Thr Cys Gly Asn Leu Leu Met 65 70 75 80 Trp Glu Ala Val Thr Val Gln Thr Glu Val Ile Gly Ile Thr Ser Met 85 90 95 Leu Asn Leu His Ala Gly Ser Gln Lys Val His Glu His Gly Gly Gly 100 105 110 Lys Pro Ile Gln Gly Ser Asn Phe His Phe Phe Ala Val Gly Gly Asp 115 120 125 Pro Leu Glu Met Gln Gly Val Leu Met Asn Tyr Arg Thr Lys Tyr Pro 130 135 140 147144PRTBK virus 147Gly Gly Val Glu Val Leu Glu Val Lys Thr Gly Leu Asp Ala Ile Thr 1 5 10 15 Glu Val Glu Cys Phe Leu Asn Pro Glu Met Gly Asp Pro Asp Glu Asn 20 25 30 Leu Arg Gly Phe Ser Leu Lys Leu Ser Ala Glu Asn Asp Phe Ser Ser 35 40 45 Asp Ser Pro Glu Arg Lys Met Leu Pro Cys Tyr Ser Thr Ala Arg Ile 50 55 60 Pro Leu Pro Asn Leu Asn Glu Asp Leu Thr Cys Gly Asn Leu Leu Met 65 70 75 80 Trp Glu Ala Val Thr Val Gln Thr Glu Val Ile Gly Ile Thr Ser Met 85 90 95 Leu Asn Leu His Ala Gly Ser Gln Lys Val His Glu His Gly Gly Gly 100 105 110 Lys Pro Ile Gln Gly Ser Asn Phe His Phe Phe Ala Val Gly Gly Asp 115 120 125 Pro Leu Glu Met Gln Gly Val Leu Met Asn Tyr Arg Thr Asn Tyr Pro 130 135 140 148144PRTBK virus 148Gly Gly Val Glu Val Leu Glu Val Lys Thr Gly Val Asp Ala Ile Thr 1 5 10 15 Glu Val Glu Cys Phe Leu Asn Pro Glu Met Gly Asp Pro Asp Glu Asn 20 25 30 Leu Arg Gly Phe Ser Leu Lys Leu Ser Ala Glu Asn Asp Phe Ser Ser 35 40 45 Asp Ser Pro Glu Arg Lys Met Leu Pro Cys Tyr Ser Thr Ala Arg Ile 50 55 60 Pro Leu Pro Asn Leu Asn Glu Asp Leu Thr Cys Gly Asn Leu Leu Met 65 70 75 80 Trp Glu Ala Val Thr Val Gln Thr Glu Val Ile Gly Ile Thr Ser Met 85 90 95 Leu Asn Leu His Ala Gly Ser Gln Lys Val His Glu His Gly Gly Gly 100 105 110 Lys Pro Ile Gln Gly Ser Asn Phe His Phe Phe Ala Val Gly Gly Asp 115 120 125 Pro Leu Glu Met Gln Gly Val Leu Leu Asn Tyr Arg Thr Asn Tyr Pro 130 135 140 149144PRTBK virus 149Gly Gly Val Glu Val Leu Glu Val Lys Thr Gly Val Asp Ala Ile Thr 1 5 10 15 Glu Val Glu Cys Phe Leu Asn Pro Glu Met Gly Asp Pro Asp Ser Asp 20 25 30 Leu Arg Gly Tyr Ser Leu Arg Leu Thr Ala Glu Thr Ala Phe Glu Ser 35 40 45 Asp Ser Pro Asp Arg Lys Met Leu Pro Cys Tyr Ser Thr Ala Arg Ile 50 55 60 Pro Leu Pro Asn Leu Asn Glu Asp Leu Thr Cys Gly Asn Leu Leu Met 65 70 75 80 Trp Glu Ala Val Thr Val Lys Thr Glu Val Ile Gly Ile Thr Ser Met 85 90 95 Leu Asn Leu His Ala Gly Ser Gln Lys Val His Glu Asn Gly Gly Gly 100 105 110 Lys Pro Ile Gln Gly Ser Asn Phe His Phe Phe Ala Val Gly Gly Asp 115 120 125 Pro Leu Glu Met Gln Gly Val Leu Met Asn Tyr Arg Thr Lys Tyr Pro 130 135 140 150144PRTBK virus 150Gly Gly Val Glu Val Leu Glu Val Lys Thr Gly Val Asp Ala Ile Thr 1 5 10 15 Glu Val Glu Cys Phe Leu Asn Pro Glu Met Gly Asp Pro Asp Glu Asn 20 25 30 Leu Arg Gly Phe Ser Leu Lys Leu Ser Ala Glu Asn Asp Phe Ser Ser 35 40 45 Asp Ser Pro Glu Arg Lys Met Leu Pro Cys Tyr Ser Thr Ala Arg Ile 50 55 60 Pro Leu Pro Asn Leu Asn Glu Asp Leu Thr Cys Gly Asn Leu Leu Met 65 70 75 80 Trp Glu Ala Val Thr Val Gln Thr Glu Val Ile Gly Ile Thr Ser Met 85 90 95 Leu Asn Leu His Ala Gly Ser Gln Lys Val His Glu His Gly Gly Gly 100 105 110 Lys Pro Ile Gln Gly Ser Asn Phe His Phe Phe Ala Val Gly Gly Asp 115 120 125 Pro Leu Glu Met Gln Gly Val Leu Leu Asn Tyr Arg Thr Lys Tyr Pro 130 135 140 151144PRTBK virus 151Gly Gly Val Glu Val Leu Glu Val Lys Thr Gly Val Asp Ala Ile Thr 1 5 10 15 Glu Val Glu Cys Phe Leu Asn Pro Glu Met Gly Asp Pro Asp Asn Asp 20 25 30 Leu Arg Gly Tyr Ser Leu Arg Leu Thr Ala Glu Thr Ala Phe Asp Ser 35 40 45 Asp Ser Pro Asn Arg Lys Met Leu Pro Cys Tyr Ser Thr Ala Arg Ile 50 55 60 Pro Leu Pro Asn Leu Asn Glu Asp Leu Thr Cys Gly Asn Leu Leu Met 65 70 75 80 Trp Glu Ala Val Thr Val Lys Thr Glu Val Ile Gly Ile Thr Ser Met 85 90 95 Leu Asn Leu His Ala Gly Ser Gln Lys Val His Glu Asn Gly Gly Gly 100 105 110 Lys Pro Ile Gln Gly Ser Asn Phe His Phe Phe Ala Val Gly Gly Asp 115 120 125 Pro Leu Lys Met Pro Gly Val Leu Met Asn Tyr Arg Thr Lys Tyr Pro 130 135 140 152144PRTBK virus 152Gly Gly Val Glu Val Leu Glu Val Lys Thr Gly Val Asp Ala Ile Thr 1 5 10 15 Glu Val Glu Cys Phe Leu Asn Pro Glu Met Gly Asp Pro Asp Asn Asp 20 25 30 Leu Arg Gly Phe Ser Leu Arg Leu Thr Ala Glu Asn Ala Phe Glu Ser 35 40 45 Asp Ser Pro Glu Arg Lys Met Leu Pro Cys Tyr Ser Thr Ala Arg Ile 50 55 60 Pro Leu Pro Asn Leu Asn Glu Asp Leu Thr Cys Gly Asn Leu Leu Met 65 70 75 80 Trp Glu Ala Val Thr Val Lys Thr Glu Val Ile Gly Ile Thr Ser Met 85 90 95 Leu Asn Leu His Ala Gly Ser Gln Lys Val His Glu Asn Gly Gly Gly 100 105 110 Lys Pro Ile Gln Gly Ser Asn Phe His Phe Phe Ala Val Gly Gly Asp 115 120 125 Pro Leu Glu Met Gln Gly Val Leu Met Asn Tyr Arg Thr Ser Tyr Pro 130 135 140 153144PRTBK virus 153Gly Gly Val Glu Val Leu Glu Val Lys Thr Gly Leu Asp Ser Ile Thr 1 5 10 15 Glu Val Glu Cys Phe Leu Asn Pro Glu Met Gly Asp Pro Glu Glu Asn 20 25 30 Leu Arg Gly Phe Ser Leu Arg Leu Ser Val Ala Asn Asp Phe Ser Ser 35 40 45 Asp Ser Pro Glu Arg Lys Met Leu Pro Cys Tyr Ser Thr Ala Arg Ile 50 55 60 Pro Leu Pro Asn Leu Asn Glu Asp Leu Thr Cys Gly Asn Leu Leu Met 65 70 75 80 Trp Glu Ala Val Thr Val Gln Thr Glu Val Ile Gly Ile Thr Ser Met 85 90 95 Leu Asn Leu His Ala Gly Ser Gln Lys Val His Glu His Gly Gly Gly 100 105 110 Lys Pro Ile Gln Gly Ser Asn Phe His Phe Phe Ala Val Gly Gly Asp 115 120 125 Pro Leu Glu Met Gln Gly Val Leu Met Asn Tyr Lys Thr Lys Tyr Pro 130 135 140 154144PRTBK virus 154Gly Gly Val Glu Val Leu Glu Val Lys Asn Gly Val Asp Ser Ile Thr 1 5 10 15 Glu Val Glu Ile Phe Leu Asn Pro Glu Met Gly Asp Pro Asp Asn Asp 20 25 30 Leu Arg Gly Tyr Ser Leu Lys Ser Ile Ser Lys Asn Asp Phe Glu Ser 35 40 45 Asp Ser Pro Asp Arg Lys Met Leu Pro Cys Tyr Ser Thr Ala Arg Ile 50 55 60 Pro Leu Pro Asn Leu Asn Glu Asp Leu Thr Cys Gly Asn Leu Leu Met 65 70 75 80 Trp Glu Ala Val Thr Val Lys Thr Glu Val Ile Gly Ile Thr Ser Met 85 90 95 Leu Asn Phe His Ala Gly Ser Gln Lys Ala His Glu Asn Gly Gly Gly 100 105 110 Lys Pro Ile Gln Gly Ser Ser Phe His Phe Phe Ala Val Gly Gly Asp 115 120 125 Pro Leu Glu Met Gln Gly Val Leu Met Asn Tyr Arg Thr Lys Tyr Pro 130 135 140 155144PRTBK virus 155Gly Gly Val Glu Val Leu Glu Val Lys Thr Gly Val Asp Ala Ile Thr 1 5 10 15 Glu Val Glu Cys Phe Leu Asn Pro Glu Met Gly Asp Pro Asp Glu Asn 20 25 30 Leu Arg Gly Phe Ser Leu Lys Leu Ser Ala Glu Asn Asp Phe Ser Ser 35 40 45 Asp Ser Pro Glu Arg Lys Met Leu Pro Cys Tyr Ser Thr Ala Arg Ile 50 55 60 Pro Leu Pro Asn Leu Asn Glu Asp Leu Thr Cys Gly Asn Leu Leu Met 65 70 75 80 Trp Glu Ala Val Thr Val Gln Thr Glu Val Ile Gly Ile Ser Ser Met 85 90 95 Leu Asn Leu His Ala Gly Ser Gln Lys Glu His Glu His Gly Gly Gly 100 105 110 Lys Pro Ile Gln Gly Ser His Phe His Phe Phe Ala Val Gly Gly Asp 115 120 125 Pro Leu Glu Met Gln Gly Val Leu Leu Asn Tyr Arg Thr Lys Tyr Pro 130 135 140 156144PRTBK virus 156Gly Gly Val Glu Val Leu Glu Val Lys Thr Gly Val Asp Ala Ile Thr 1 5 10 15 Glu Val Glu Cys Phe Leu Asn Pro Glu Met Gly Asp Pro Glu Glu Lys 20 25 30 Leu Asn Gly Phe Ser Leu Lys Leu Ser Ala Glu Asn Asp Phe Ser Ser 35 40 45 Asp Ser Pro Glu Arg Lys Met Leu Pro Cys Tyr Ser Thr Ala Arg Ile 50 55 60 Pro Leu Pro Asn Leu Asn Glu Asp Leu Thr Cys Gly Asn Leu Leu Met 65 70 75 80 Trp Glu Ala Val Thr Val Gln Thr Glu Val Ile Gly Ile Thr Ser Met 85 90 95 Leu Asn Leu His Ala Gly Ser Gln Lys Glu His Glu His Gly Gly Gly 100 105 110 Lys Pro Ile Gln Gly Ser His Phe His Phe Phe Ala Val Gly Gly Asp 115 120 125 Pro Leu Glu Met Gln Gly Val Leu Leu Asn Tyr Arg Thr Lys Tyr Pro 130 135 140 157144PRTBK virus 157Gly Gly Val Glu Val Leu Glu Val Lys Thr Gly Val Asp Ser Ile Thr 1 5 10 15 Glu Val Glu Cys Phe Leu Asn Pro Glu Met Gly Asp Pro Asp Glu Ser 20 25 30 Phe Arg Gly Phe Ser Leu Lys Leu Ser Ala Glu Asn Asp Ile Ser Ser 35 40 45 Asp Asn Pro Glu Arg Lys Met Leu Pro Cys Tyr Ser Thr Ala Arg Ile 50 55 60 Pro Leu Pro Asn Leu Asn Glu Asp Leu Thr Cys Gly Asn Leu Leu Met 65 70 75 80 Trp Glu Ala Val Thr Val Gln Thr Glu Val Ile Gly Ile Ser Ser Met 85 90 95 Leu Asn Leu His Ala Gly Ser Gln Lys Val His Glu His Gly Gly Gly 100 105 110 Lys Pro Ile Gln Gly Ser Asn Phe His Phe Phe Ala Val Gly Gly Asp 115 120 125 Pro Leu Lys Met Gln Gly Val Leu Leu Asn Tyr Arg Thr Ser Tyr Pro 130 135 140 158144PRTBK virus 158Gly Gly Val Glu Val Leu Glu Val Lys Thr Gly Val Asp Ala Ile Thr 1 5 10 15 Glu Val Glu Ser Phe Leu Asn Pro Glu Met Gly Asp Pro Glu Glu Thr 20 25 30 Phe Arg Gly Phe Ser Leu Lys Gln Ser Ser Glu Lys Asp Ile Ser Asn 35 40 45 Asp Ser Pro Lys Lys Lys Met Leu Pro Cys Tyr Ser Thr Ala Arg Ile 50 55 60 Pro Leu Pro Asn Leu Asn Glu Asp Leu Thr Cys Gly Asn Leu Leu Met 65 70 75 80 Trp Glu Ala Val Thr Val Gln Thr Glu Val Ile Gly Ile Thr Ser Met 85 90 95 Leu Asn Leu His Ala Gly Ser Gln Lys Val His Glu His Gly Gly Gly 100 105 110 Lys Pro Ile Gln Gly Ser His Val His Phe Phe Ala Val Gly Gly Asp 115 120 125 Pro Leu Lys Met Gln Gly Val Val Met Asn Tyr Lys Thr Lys Tyr Pro 130 135

140

Claims

1. A multivalent BK polyomavirus (BKV) immunogenic composition comprising: a virus-like particle comprising at least one BKV serotype IV capsid polypeptide; a virus-like particle comprising at least one BKV serotype I capsid polypeptide; a pharmaceutically acceptable carrier; and an adjuvant.

2. The composition of claim 1, wherein the at least one BKV-IV capsid polypeptide comprises the amino acid sequence of any one of SEQ ID NOs: 4-6, 16, and 110-125 and the at least one isolated BKV-I capsid polypeptide comprises the amino acid sequence of any one of SEQ ID NOs: 1-3, 13-15, and 52-103.

3. The composition of claim 1, further comprising: a virus-like particle comprising at least one BKV serotype II capsid polypeptide; a virus-like particle comprising at least one BKV serotype III capsid polypeptide; or a combination thereof.

4. The composition of claim 1, wherein the at least one capsid polypeptide comprises VP1, VP2, VP3, or a combination of two or more thereof.

5. The composition of claim 1, wherein the at least one BKV serotype IV capsid polypeptide comprises one or more of a BKV-IVb1 VP1 polypeptide and/or a BKV-IVc2 VP1 polypeptide.

6. The composition of claim 5, wherein the BKV-IVb1 VP1 polypeptide is encoded by a nucleic acid molecule comprising the sequence of SEQ ID NO: 47 and/or the BKV-IVc2 VP1 polypeptide is encoded by a nucleic acid molecule comprising the sequence of SEQ ID NO: 27 or 39.

7. The composition of claim 1, wherein the at least one BKV serotype I capsid polypeptide comprises one or more of a BKV-Ia VP1 polypeptide, a BKV-Ib1 VP1 polypeptide, a BKV-Ib2 VP1 polypeptide, and/or a BKV-Ic VP1 polypeptide.

8. The composition of claim 7, wherein the BKV-Ia VP1 polypeptide is encoded by a nucleic acid molecule comprising the sequence of SEQ ID NO: 42, the BKV-Ib1 VP1 polypeptide is encoded by a nucleic acid molecule comprising the sequence of SEQ ID NO: 24; the BKV-Ib2 VP1 polypeptide is encoded by a nucleic acid molecule comprising the sequence of SEQ ID NO: 43; and/or the BKV-Ic VP1 polypeptide is encoded by a nucleic acid molecule comprising the sequence of SEQ ID NO: 44.

9. The composition of claim 1, wherein the virus-like particle comprising at least one BKV-IV capsid polypeptide comprises a BKV-IV VP1 polypeptide, and the virus-like particle comprising at least one BKV-I capsid polypeptide comprises a BKV-Ia VP1 polypeptide and/or a BKV-Ib2 VP1 polypeptide.

10. The composition of claim 1, further comprising a virus-like particle comprising at least one JC polyomavirus capsid polypeptide.

11. A multivalent BK polyomavirus (BKV) immunogenic composition comprising: a virus-like particle comprising at least one BKV serotype IV VP1 polypeptide, wherein the at least one BKV serotype IV VP1 polypeptide is encoded by a nucleic acid molecule comprising the sequence of SEQ ID NO: 39 or SEQ ID NO: 47; a virus-like particle comprising at least one BKV serotype I VP1polypeptide, wherein the at least one BKV serotype I VP1 polypeptide is encoded by a nucleic acid molecule comprising the sequence of one of SEQ ID NOs: 42-44; and a pharmaceutically acceptable carrier.

12. The composition of claim 11, wherein the at least one BKV-IV VP1 polypeptide comprises the amino acid sequence of SEQ ID NO: 4 or SEQ ID NO: 16 and/ot the at least one isolated BKV-I VP1 polypeptide comprises the amino acid sequence of any one of SEQ ID NOs: 1 and 13-15.

13. The composition of claim 11, further comprising: a virus-like particle comprising at least one BKV serotype II capsid polypeptide; a virus-like particle comprising at least one BKV serotype III capsid polypeptide; or a combination thereof.

14. The composition of claim 11, wherein the virus-like particle further comprises a VP2 polypeptide, a VP3 polypeptide, or a combination of two or more thereof.

15. The composition of claim 11, wherein the at least one BKV serotype IV VP1 polypeptide comprises one or more of a BKV-IVb1 VP1 polypeptide and/or a BKV-IVc2 VP1 polypeptide.

16. The composition of claim 11, wherein the at least one BKV serotype I VP1 polypeptide comprises one or more of a BKV-Ia VP1 polypeptide, a BKV-Ib1 VP1 polypeptide, a BKV-Ib2 VP1 polypeptide, and/or a BKV-Ic VP1 polypeptide.

17. The composition of claim 11, wherein the virus-like particle comprising at least one BKV-IV VP1 polypeptide comprises a BKV-IV VP1 polypeptide, and the virus-like particle comprising at least one BKV-I VP1 polypeptide comprises a BKV-Ia VP1 polypeptide and/or a BKV-Ib2 VP1 polypeptide.

18. The composition of claim 11, further comprising a virus-like particle comprising at least one JC polyomavirus capsid polypeptide.

19. The composition of claim 11, further comprising an adjuvant.