# Patent

## Title
Method for identifying and producing a protease capable of cleaving the

## Abstract

The protease necessary for polyprotein processing in Hepatitis G virus (HGV) is identified, cloned, and expressed. Proteases, truncated protease, and altered proteases are disclosed which are useful for cleavage of specific polypeptides, and for assay and design of antiviral agents specific for HGV.

## Background
The present invention relates to the molecular biology and virology of the hepatitis G virus (HGV). More specifically, this invention relates to a novel protease produced by HGV, methods of expression, recombinant protease, protease mutants, inhibitors of HGV protease, HGV polypeptide antigens and methods for producing HGV polypeptides.

Non-A, Non-B, Non-C, Non-D, Non-E hepatitis (Non-A-E hepatitis) is a transmissible disease (or family of diseases) that is believed to be virally induced, and is distinguishable from other forms of virus-associated liver disease, such as those caused by hepatitis A virus (HAV), hepatitis B virus (HBV), hepatitis C virus (HCV), delta hepatitis virus (HDV), hepatitis E virus, (HEV) cytomegalovirus (CMV), or Epstein-Barr virus (EBV). Recently a new viral species, hepatitis G virus (HGV) has been identified as associated with Non-A-E hepatitis. See, for example, PCT US95/06169, incorporated herein by reference. HGV infection has been associated with post-transfusion non-A-E hepatitis, chronic non-A-C hepatitis, hepatocellular carcinoma, transfusion associated anemia, and other diseases. Furthermore, HGV infection has been shown to exist in 1.7% of blood donors in the United States and infection with HGV has been shown to be transfusion transmissible (Linnen et al, Science (1996) 271:505). Thus, the need exists for an effective method for diagnosing and treating HGV infection.

Many viruses, including adenoviruses, baculoviruses, comoviruses, picornaviruses, flaviviruses, retroviruses, and togaviruses, rely on specific, virally-encoded proteases for processing polypeptides from their initial translated form into mature, active proteins. In the case of picornaviruses, all of the viral proteins are believed to arise from cleavage of a single polyprotein (B. D. Korant, CRC Crit Rev Biotech (1988) 8:149-57). A serine protease has been described for Hepatitis C virus, M. Houghton et al., U.S. Pat. No. 5,371,017. A co-factor to such a serine protease described by Houghton, supra, was described by Y. Tanji et al, J Virol, (1995) 69(3):1575. A second HCV protease was further described in M. Hijikata, J Virol, (1993) 67(8):4665.

Proteases have recently become a target of choice for developing antiviral therapeutics. For example, T. J. McQuade et al, Science (1990) 247:454-56 disclosed preparation of a peptide mimic capable of specifically inhibiting the HIV-1 protease. In HIV, the protease is believed responsible for cleavage of the initial p55 gag precursor into the core structural proteins (p17, p24, p8, and p7). Adding 1 uM inhibitor to HIV-infected peripheral blood lymphocytes in culture reduced the concentration of processed HIV p24 by about 70%. Viral maturation and levels of infectious virus were reduced by the protease inhibitor.

It is one object of the invention to provide an HGV protease composition comprising a purified proteolytic polypeptide complex derived from Hepatitis G virus. In one embodiment of the invention the HGV protease comprises a polypeptide having a partial internal sequence substantially as encoded by SEQ ID NO:3. In another embodiment said polypeptide complex comprises a polypeptide having a partial internal sequence substantially as encoded by SEQ ID NO:4. In a third embodiment the protease comprises a co-factor having a partial internal sequence substantially as identified by SEQ ID NO:5.

Also included in the invention is a fusion protein, comprising a fusion partner fused to a proteolytic polypeptide derived from Hepatitis G virus. In one embodiment the proteolytic polypeptide derived from Hepatitis G virus is substantially encoded by SEQ ID NO:24.

In a further aspect, the invention includes a composition comprising a polynucleotide which encodes an HGV protease complex or an active HGV protease complex analog.

Yet another aspect of the invention includes a method for producing a purified HGV protease. Such method includes the steps of: (a) transforming a host cell with a vector containing a foreign DNA encoding an HGV protease, (b) subjecting the host cell to conditions required for expression of the HGV protease, and (c) purifying the protease.

A related aspect of the invention includes a method for assaying compounds for activity against hepatitis G virus, comprising the steps of: (a) providing an active hepatitis G virus protease: (b) contacting said protease with a compound capable of inhibiting protease activity; and (c) measuring inhibition of the proteolytic activity of said hepatitis G virus protease.

FIG. 1 shows regions of the HGV genome which were inserted into recombinant baculoviruses as they align with a schematic of the HGV polyprotein.

FIG. 2 shows a schematic of recombinant baculovirus vectors containing HGV protease inserts and an SDS-PAGE of extracts of Sf21 insect cells which had been infected with the recombinant viruses shown.

FIG. 3 shows a schematic diagram representing the co-infection of recombinant baculoviruses, one containing an HGV protease and a second containing an HGV polyprotein cleavage substrate. The purified GST fusion proteins are shown as analyzed by SDS-PAGE.

FIG. 4 shows various recombinant baculovirus constructs used to determine the proteolytic regions of HGV necessary for cleavage at the NS4/NS5 junction. Also, contained in FIG. 4 are two western blots of the same SDS-PAGE, using either anti-GST (top) or anti-NS4B as the reporter (bottom).

FIG. 5 shows an SDS-PAGE of insect cell lysates infected with one or more HGV constructs indicated schematically and designed to demonstrate cleavage at the NS5A/NS5B junction.

A. Definitions

The terms "Hepatitis G Virus" and "HGV" refer to the viral species that is identified in PCT US95/06169, the disclosure of which are incorporated herein by reference. The HGV genome is comprised of RNA. It is known that RNA-containing viruses have relatively high rates of spontaneous mutation, reportedly on the order of 10.sup.-3 to 10.sup.-4 per incorporated nucleotide (Wieds & Knipe, "Fundamental Virology" (1986, Raven Press, N.Y.)). As heterogenicity and fluidity of genotype are inherent characteristics of RNA viruses, there will be multiple strains/isolates, which may be virulent or avirulent, within the HGV species.

Information on several different strains/isolates of HGV is disclosed herein, particularly strain or isolate PNF-2161. Information from one strain or isolate, such as a partial genome sequence, is sufficient to allow those skilled in the art using standard techniques to isolate new strains/isolates and to identify whether such new strains/isolates are HGV. For example, several different strains/isolates are described below. These strains, which were obtained from a number of human sera (and from different geographical areas), were isolated utilizing the information from the genomic sequence of PNF-2161.

The information provided herein suggests that HGV may be distantly related to the flaviviridae, including Hepatitis C Virus. The Flaviviridae family contains a large number of viruses which are small, enveloped pathogens of man. The morphology and composition of Flavivirus particles are known, and are discussed in M. A. Brinton, in "The Viruses: The Togaviridae And Flaviviridae" (series eds. Fraenkel-Contrat and Wagner, vol. eds. Schlessinger and Schlessinger, Plenum Press, 1986), pp. 327-374. Generally, with respect to morphology, flaviviruses contain a central nucleocapsid surrounded by a lipid bilayer. Virions are spherical and have a diameter of about 40-50 nm. Their cores are about 25-30 nm in diameter. Along the outer surface of the virion envelope are projections measuring about 5-10 nm in length with terminal knobs about 2 nm in diameter. Typical examples of the family include Yellow Fever virus, West Nile virus, and Dengue Fever virus. They possess positive-stranded RNA genomes (about 11,000 nucleotides) that are slightly larger than that of HGV and encode a precursor of about 3500 amino acids. Individual proteins are cleaved from this precursor polypeptide.

The genome of HGV appears to be single-stranded RNA containing about 9400 nucleotides. The genome is positive-stranded, and possesses a continuous translational open reading frame (ORF) that encodes a polyprotein of about 2,900 amino acids. In the ORF, the structural proteins appear to be encoded in approximately the first quarter of the N-terminal region, with the majority of the polyprotein attributed to non-structural proteins. When compared with all known viral sequences, small but significant co-linear homologies are observed with the nonstructural proteins of the Flaviviridae family, and with the pestiviruses (which are now also considered to be part of the Flaviviridae family).

A schematic of a putative polyprotein encoded in the major ORF of the HGV genome is shown in FIG. 1. Probable genes of the HGV polyprotein are indicated in the figure. The Hepatitis G Virus polyprotein contains, from the amino terminus to the carboxy terminus, the nucleocapsid-like protein (C), the envelope proteins (El and E2), and the non-structural proteins (NS2a, NS2b, NS3, NS4a-NS4b, NS5a, NS5b). The polyprotein of HGV differs significantly from other flaviviruses in size and sequence, particularly in the structural gene regions where there is almost no homology. Furthermore, the untranslated regions of HGV appear to be quite distinct from HCV. Also, there may be considerable differences between the HGV and the flaviviruses, and HCV in particular, that have yet to be appreciated.

Due to the evolutionary relationship of the strains or isolates of HGV, putative HGV strains and isolates are identifiable by their sequence homology. "HGV variants" are defined as viral isolates that have at least about 55% global sequence homology, that is, sequence identity over a length (at least comparable to SEQ ID NO:1) of the viral genome polynucleotide sequence, to the HGV polynucleotide sequences disclosed herein. "Sequence homology" is determined essentially as follows. Two polynucleotide sequences of the same length (preferably, the entire viral genome) are considered to be homologous to one another, if, when they are aligned using the ALIGN program, over, preferably 55%, more preferable 60%, even more preferably 70%, or most preferably 80% of the nucleic acids in the highest scoring alignment are identically aligned using a ktup of 1, the default parameters and the default PAM matrix.

The ALIGN program is found in the FASTA version 1.7 suite of sequence comparison programs (Pearson, et al., 1988; Pearson, 1990; program available from William R. Pearson, Department of Biological Chemistry, Box 440, Jordan Hall, Charlottesville, Va.).

In determining whether two viruses are "highly homologous" to each other, the complete sequence of all the viral proteins (or the polyprotein) for one virus are optimally, globally aligned with the viral proteins or polyprotein of the other virus using the ALIGN program of the above suite using a ktup of 1, the default parameters and the default PAM matrix. Regions of dissimilarity or similarity are not excluded from the analysis. Differences in lengths between the two sequences are considered as mismatches. Highly homologous viruses have over, preferably 55%, more preferable 60%, even more preferably 70%, or most preferably 80% global polypeptide sequence identity.

Two nucleic acid fragments are considered to be "selectively hybridizable" to an HGV polynucleotide, if they are capable of specifically hybridizing to HGV or a variant thereof (e.g., a probe that hybridizes to HGV nucleic acid but not to polynucleotides from other members of the virus family Flaviviridae) or specifically priming a polymerase chain reaction: (i) under typical hybridization and wash conditions, as described, for example, in Maniatis, et al., pages 320-328, and 382-389, or (ii) using reduced stringency wash conditions that allow at most about 25-30% basepair mismatches, for example: 2.times.SSC, 0.1% SDS, room temperature twice, 30 minutes each; then 2.times.SSC, 0.1% SDS, 37.degree. C. once, 30 minutes; then 2.times.SSC room temperature twice, 10 minutes each, or (iii) selecting primers for use in typical polymerase chain reactions (PCR) under standard conditions (for example, in Saiki, R. K, et al.), which result in specific amplification of sequences of HGV or its variants.

Preferably, highly homologous nucleic acid strands contain less than 20-30% basepair mismatches, even more preferably less than 5-20% basepair mismatches. These degrees of homology can be selected by using wash conditions of appropriate stringency for identification of clones from gene libraries (or other sources of genetic material), as is well known in the art.

An "HGV polynucleotide," as used herein, is defined as follows. For polynucleotides greater than about 100 nucleotides, HGV polynucleotides encompass polynucleotide sequences encoded by HGV variants and homologous sequences as defined in "2" above. For polynucleotides less than about 100 nucleotides in length, HGV polynucleotide encompasses sequences that selectively hybridizes to sequences of HGV or its variants. Further, HGV polynucleotides include polynucleotides encoding HGV polypeptides (see below).

An "HGV polypeptide" is defined herein as any polypeptide homologous to an HGV polypeptide. "Homology," as used herein, is defined as follows. In one embodiment, a polypeptide is homologous to an HGV polypeptide if it is encoded by nucleic acid that selectively hybridizes to sequences of HGV or its variants.

In another embodiment, a polypeptide is homologous to an HGV polypeptide if it is encoded by HGV or its variants, as defined above, polypeptides of this group are typically larger than 15, preferable 25, or more preferable 35, contiguous amino acids. Further, for polypeptides longer than about 60 amino acids, sequence comparisons for the purpose of determining "polypeptide homology" are performed using the local alignment program LALIGN. The polypeptide sequence, is compared against the HGV amino acid sequence or any of its variants, as defined above, using the LALIGN program with a ktup of 1, default parameters and the default PAM.

Any polypeptide with an optimal alignment longer than 60 amino acids and greater than 65%, preferably 70%, or more preferably 80% of identically aligned amino acids is considered to be a "homologous polypeptide." The LALIGN program is found in the FASTA version 1.7 suite of sequence comparison programs (Pearson, et al., 1988; Pearson, 1990; program available from William R. Pearson, Department of Biological Chemistry, Box 440, Jordan Hall, Charlottesville, Va.).

A polynucleotide is "derived from" HGV if it has the same or substantially the same basepair sequence as a region of an HGV genome, cDNA of HGV or complements thereof, or if it displays homology as noted under "2", "3" or "4" above.

A polypeptide is "derived from" HGV if it is (i) encoded by an open reading frame of an HGV polynucleotide, or (ii) displays homology to HGV polypeptides as noted under "2" and "5" above, or (iii) is specifically immunoreactive with HGV positive sera.

"Substantially isolated" is used in several contexts and typically refers to the at least partial purification of an HGV virus particle, component (e.g., polynucleotide or polypeptide), or related compound (e.g., anti-HGV antibodies) away from unrelated or contaminating components (e.g., serum cells, proteins, and non-anti-HGV antibodies). Methods and procedures for the isolation or purification of compounds or components of interest are described below (e.g., affinity purification of fusion proteins and recombinant production of HGV polypeptides).

In the context of the present invention, the phrase "nucleic acid sequences," when referring to sequences which encode a protein, polypeptide, or peptide, is meant to include degenerative nucleic acid sequences which encode homologous protein, polypeptide or peptide sequences as well as the disclosed sequence.

The term "HGV protease" refers to enzymes, and enzyme-cofactor complexes, derived from HGV which exhibit proteolytic activity, specifically the polypeptides encoded in the NS2B, NS3, and NS4 domains of the HGV genome. As described in Examples 5 and 6, the NS2B-NS3-NS4 region of HGV encodes multiple protease activities. The NS3 serine protease is shown, for example in Example 6, to be responsible for cleavage at the NS5A/NS5B junction, and can act in a complex with an NS4-encoded cofactor to cleave at the NS4A-B/NS5A junction. These activities both can occur in trans. Furthermore, as described, for example in Example 5, NS3 contains a cis-acting autocatalytic activity for cleavage at the NS3/NS4A-B junction. This autocatalytic activity also appears to be NS4A-B cofactor independent. As shown, for example in Example 6, NS2B encodes a second protease activity which is necessary for cleavage at the NS2B/NS3 junction.

At least one strain of HGV contains an NS2B protease believed to be substantially encoded by or within SEQ ID NO:3, an NS3 protease believed to be substantially encoded by or within SEQ ID NO:4, and an NS4 cofactor believed to be substantially encoded by or within SEQ ID NO:5. The amino and carboxy termini of the polypeptides encoded by the sequences shown in SEQ ID NOS:3, 4, and 5 are putative boundaries necessary for enzyme activity. It is understood that this sequence may vary from strain to strain, as RNA viruses like HGV are known to exhibit a great deal of variation. Further, the actual amino and carboxy termini may vary, as the protease is cleaved from a precursor polyprotein: variations in the protease amino acid sequence can result in cleavage from the polyprotein at difference points. Thus the amino- and carboxy-termini may differ from strain to strain in HGV. Furthermore, HGV protease activity may be to a greater or lesser extent, conformationally dependent. Therefore, activity may be greater when the HGV protease is expressed a part of the larger HGV polyprotein as it is naturally. However, the minimum sequence necessary for activity can be determined by routine methods. The sequence may be truncated at either end by treating an appropriate expression vector with an exonuclease (after cleavage at the 5' or 3' end of the coding sequence) to remove any desired number of base pairs. The resulting coding polynucleotide is then expressed and the sequence determined. In this manner the activity of the resulting product may be correlated with the amino acid sequence: a limited series of such experiments (removing progressively greater numbers of base pairs) determines the minimum internal sequence necessary for protease activity. It is presently believed that a portion of the protein at the carboxy terminus may exhibit helicase activity. However, helicase activity is not required of the HGV proteases of the invention.

The amino acids His.sub.849, Asp.sub.890, and Ser.sub.1062 are believed to be the residues necessary for catalytic activity of NS3, based on sequence homology to the putative flavivirus proteases. Table 1 shows the alignment of the three catalytic residues for HGV protease with the same region from other flaviviruses. __________________________________________________________________________ Protease Histidine      Asparagine     Serine __________________________________________________________________________ HGV    LETTFHGAS (SEQ ID NO: 6) ASDDVTVYP (SEQ ID ND: 7) FRGSSGSPV (SEQ ID NO: 8) HCV    CWTVYHGAG (SEQ ID NO: 9) DODLGWPAP (SEQ ID NO: 10) LKGSSGGPL (SEQ ID NO: 11) Yellow Fever FHTMWHVTR (SEQ ID NO: 12) KEDLVATGG (SEQ ID NO: 13) PSGTSGSPI (SEQ ID NO: 14) West Nile FHTLWNTTK (SEQ ID NO: 15) KEDRLCYGG (SEQ ID NO: 16) PTGTSGSPI (SEQ ID NO: 17) Murray Valley FHTLWHTTR (SEQ ID NO: 18) KEDRVTYGG (SEQ ID NO: 19) PTGTSGSPI (SEQ ID NO: 20) Kunjin Virus FHTLWHTTK (SEQ ID NO: 21) KEDRLCYGG (SEQ ID NO: 22) PTGTSGSPI (SEQ ID NO: __________________________________________________________________________ 23)

The most direct way to verify the residues essential to the active site of a protease is to replace each residue individually with a different residue. This is easily accomplished by site-specific mutagenesis and similar techniques known in the art. If replacement of a particular residue results in a loss of activity, the essential nature of the replaced residue is confirmed. Such experiments are described in Examples 2 and 5.

An HGV protease construct "L" described in Examples 2 and 3, below, is shown as SEQ ID NO:24. This construct contains the carboxy-terminal NS2B, NS3 and amino-terminal NS4A regions from PNF-2161. This construct is shown to have complete protease activity at the NS2B/NS3, NS3/NS4A-B, NS4A-B/NS5A and NS5A/NS5B junctions. An NS2B mutant with His.sub.849 to Tyr change is shown as SEQ ID NO:26. This construct is shown in Example 5 to lose cleavage activity at the NS2B/NS3 junction. Likewise, a second NS2B mutant with Cys.sub.890 to Leu change is shown as SEQ ID NO:28. This construct is shown in Example 5 to lose cleavage activity at the NS2B/NS3 junction. An NS3 mutant with an Ser.sub.1062 to Ala, described in Example 5, is shown as SEQ ID NO:30. This mutant is shown in Example 5 to lose cleavage activity at NS3/NS4A-B, NS4A-B/NS5A, NS5A/NS5B. "HGV protease analogs" refer to polypeptides which vary from the full length protease sequence by deletion, alteration and/or addition to the amino acid sequence of the native protease. HGV protease analogs include the HGV protease mutants described above, and fusion proteins comprising HGV protease, truncated protease, or protease mutants. Typically, the total number of residues changed, deleted or added to the native sequence in the mutants will be no more that about 20, preferably no more than about 10, and most preferably no more than about 5.

The term fusion protein generally refers to a polypeptide comprising an amino acid sequence drawn from two or more individual proteins. In the present invention, "fusion protein" is used to denote a polypeptide comprising the HGV protease, truncate, mutant or functional portion thereof, fused to a non-HGV protein polypeptide ("fusion partner"). Fusion proteins are most conveniently produced by expression of a fused gene, which encodes a portion of one polypeptide at the 5' end and a portion of a different polypeptide at the 3' end, where the different portions are joined in one reading frame which may be expressed in a suitable host. It is presently preferred (although not required) to position the HGV protease or analog at the carboxy terminus of the fusion protein. As the HGV protease is normally expressed within a large polyprotein, it is not expected to include cell transport signals (e.g., export or secretion signals). Suitable functional enzyme fragments are those polypeptides which exhibit quantifiable activity when expressed fused to the HGV protease. Exemplary enzymes include, without limitation, Beta-galactosidase (B-gal), Beta-lactamase, horseradish peroxidase (HRP), glucose oxidase (GO), human superoxide dismutase (hSOD), urease, and the like. These enzymes are convenient because the amount of fusion protein produced can be quantified by means of simple calorimetric assays. Alternatively, one may employ antigenic proteins or fragments, to permit simple detection and quantification of fusion proteins using antibodies or substrates specific for the fusion partner, such as glutathione-S-transferase or even another HGV fragment. The presently preferred fusion partner is glutathione-S-transferase (GST).

An "epitope" is the area of an antigenic molecule (antigen) that determines the specific antibody to which the antigen binds. An antigen or epitope is "specifically immunoreactive" with HGV positive sera when the antigen or epitope binds to antibodies present in the HGV infected sera but does not bind to antibodies present in the majority (greater than about 90%, preferably greater than 95%) of sera from individuals who are not or have not been infected with HGV. "Specifically immunoreactive" antigens or epitopes may also be immunoreactive with monoclonal or polyclonal antibodies generated against specific HGV epitopes or antigens.

An antibody or antibody composition (e.g., polyclonal antibodies) is "specifically immunoreactive" with HGV when the antibody or antibody composition is immunoreactive with an HGV antigen but not with HAV, HBV, HCV, HDV or HEV antigens. Further, "specifically immunoreactive antibodies" are not immunoreactive with antigens typically present in normal sera, not infected with or exposed to HGV.

B. General Methods

The practice of the present invention generally employs conventional techniques of molecular biology, microbiology, recombinant DNA, and immunology, which are within the skill of the art. Such techniques are explained fully in the literature. See for example J. Sambrook et al, "Molecular Cloning; A Laboratory Manual" (1989); "DNA Cloning", Vol. I and II (D. N. Glover ed. 1985); "Oligonucleotide Synthesis" (M. J. Gait ed., 1984); "Nucleic Acid Hybridization" (B. D. Hames & S. J. Higgins eds. 1984); "Transcription And Translation" (B. D. Hames & S. J. Higgins eds. 1984); "Animal Cell Culture" (R. I. Freshney ed. 1986); "Immobilized Cells And Enzymes" (IRL Press, 1986); B. Perbal, "A Practical Guide To Molecular Cloning" (1984); the series "Methods In Enzymology" (Academic Press, Inc.); "Gene Transfer Vectors For Mammalian Cells" (J. H. Miller and M. P. Calos eds. 1987, Cold Spring Harbor Laboratory); Meth Enzymology (1987) 154 and 155 (Wu and Grossman, and Wu, eds., respectively); Mayer & Walker, eds. (1987); "Immunochemical Methods In Cell And Molecular Biology" (Academic Press, London); Scopes, and "Handbook Of Experimental Immunology", volumes I-IV (Weir and Blackwell eds., 1986).

Both prokaryotic and eukaryotic host cells are useful for expressing desired coding sequences when appropriate control sequences compatible with the designated host are used, and are known in the art and are commercially available. Mammalian cell lines available as hosts for expression are known in the art and include many immortalized cell lines available from the American Type Culture Collection (ATCC). Suitable promoters for mammalian cells are also known. Mammalian cells may also require terminator sequences and poly-A addition sequences. Enhancer sequences which increase expression may also be included, and sequences which promote amplification of the gene may also be desirable. These genes are known in the art.

Vectors suitable for replication in mammalian cells are known in the art. For example, a vector used to express foreign DNA is Vaccinia virus. In this case the heterologous DNA is inserted into the Vaccinia genome. Techniques for the insertion of foreign DNA into the vaccinia virus genome are known in the art, and may utilize, for example, homologous recombination. The heterologous DNA is generally inserted into a gene which is non-essential to the virus, for example, the thymidine kinase gene (tk), which also provides a selectable marker. Plasmid vectors that greatly facilitate the construction of recombinant viruses have been described (see, for example, Mackett et al, J Virol (1984) 49:857; Chakrabarti et al, Mol Cell Biol (1985) 5:3403; Moss, in GENE TRANSFER VECTORS FOR MAMMALIAN CELLS (Miller and Calos, eds., Cold Spring Harbor Laboratory Press, N.Y., 1987), p. 10, and Ward et al, Proc Nat Acad Sci (1995) 92:6773).

Other systems for expression of eukaryotic or viral genomes include insect cells and vectors suitable for use in these cells. These systems are known in the art, and include, for example, insect expression transfer vectors derived from the baculovirus Autographa californica nuclear polyhedrosis virus (AcNPV), which is a helper independent, viral expression vector. Expression vectors derived from this system usually use the strong viral polyhedrin gene promoter to drive expression of heterologous genes. Currently the most commonly used transfer vector for introducing foreign genes into AcNPV is pACYM1; see Y. Matsuura, et al, J Gen Virol, (1987) 68:1233. Many other vectors known to those of skill in the art have also been designed for improved expression.

Methods for the introduction of heterologous DNA into the desired site in the baculovirus are known in the art. (See Summer and Smith, Texas Agricultural Experiment Station Bulletin No. 1555; Smith et al, Mol Cell Biol (1983) 3:2156-2165; and Luckow and Summers, Virol (1989) 17:31).

The signals for post-translational modifications, such as signal peptide cleavage, proteolytic cleavage, and phosphorylation, appear to be recognized by insect cells. The signals required for secretion and nuclear accumulation also appear to be conserved between the invertebrate cells and vertebrate cells.

Transformation may be by any known method for introducing polynucleotides into a host cell, including, for example, packaging the polynucleotide in a virus and transducing a host cell with the virus, and by direct uptake of the polynucleotide. The transformation procedure depends on the host to be transformed. Bacterial transformation by direct uptake generally employs treatment with calcium or rubidium chloride (Cohen, Proc Nat Acad Sci USA (1978) 75:1929. Mammalian transformation by direct uptake may be conducted using the calcium phosphate precipitation method of Graham and Van der Eb, Virol (1978) 52:546, or the various known modifications thereof. Alternatively, as is commonly used in the art, a lipofection transfection technique may be used; see P. Kitts et al., Biotechniques, (1993) 14(5):810.

DNA sequences, including those isolated from cDNA libraries, may be modified by known techniques, for example site-directed mutagenesis (see e.g., Zoller, Nuc Acids Res (1982) 10:6487). Commercially available kits for modifying DNA sequences can be obtained from many sources known to those of skill in the art, for example, Stratagene Cloning Systems, Inc., La Jolla, Calif.

The enzyme-linked immunosorbent assay (ELISA) can be used to measure either antigen or antibody concentrations. This method depends upon conjugation of an enzyme to either an antigen or an antibody, and uses the bound enzyme activity as a quantitative label. To measure antibody, the known antigen is fixed to a solid phase (e.g., a microtitre dish, plastic cup, dipstick, plastic bead, or the like), incubated with test serum dilutions, washed, incubated with anti-immunoglobulin labeled with an enzyme, and washed again. Enzymes suitable for labelling are known in the art, and include, for example, horseradish peroxidase (HRP). Enzyme activity bound to the solid phase is usually measured by adding a specific substrate, and determining product formation or substrate utilization calorimetrically. The enzyme activity bound is a direct function of the amount of antibody bound.

To measure antigen, a known specific antibody is fixed to the solid phase, the test material containing antigen is added, after an incubation the solid phase is washed, and a second enzyme-labeled antibody is added. After washing, substrate is added, and enzyme activity is measured calorimetrically, and related to antigen concentration.

Proteases of the invention may be assayed for activity by cleaving a substrate which provides detectable cleavage products. As the HGV protease is believed to cleave itself from the genomic polyprotein, one can employ this autocatalytic activity both to assay expression of the protein and determine activity. For example, if the protease is joined to its fusion partner so that an HGV protease cleavage substrate is provided, the expression product will cleave itself into fusion partner and active HGV protease. One may then assay the products, for example, by polyacrylamide gel electrophoresis or western blot, to verify that the proteins produced correspond in size to the separate fusion partner and protease proteins, as is the presently preferred method. Alternatively one may employ small peptide p-nitrophenyl esters or methylcoumarins, as cleavage may then be followed by spectrophotometric or fluorescent assays. Following the method described by E. D. Matayoshi et al, Science (1990) 247:231-35, one may attach a fluorescent label to one end of the substrate and a quenching molecule to the other end: cleavage is then determined by measuring the resulting increase in fluorescense. If a suitable enzyme or antigen has been employed as the fusion partner, the quantity of protein produced may easily be determined. Further, one may exclude the HGV protease n-terminal cleavage signal (preventing self-cleavage) and add a separate cleavage substrate, such as a fragment of the HGV NS3 domain including the native processing signal or a synthetic analog.

In the absence of this protease activity, the HGV polyprotein should remain in its unprocessed form, and thus render the virus noninfectious. Thus, the protease is useful for assaying pharmaceutical agents for control of HGV, as compounds which inhibit the protease activity sufficiently will also inhibit viral infectivity. Such inhibitors may take the form of organic compounds, particularly compounds which mimic the cleavage site of HGV recognized by the protease. Three of the putative cleavage sites of the HGV polyprotein are shown below:

The cleavage junctions between: NS2A/NS2B is between Gly.sub.693 -Ala; NS2B/NS3 is between Thr.sub.925 -Ala; and NS4B-NS5A is between Gly.sub.1898 -Tyr. The other junctions may be determined by techniques known to those of skill in the art, for example by the method of Example 7.

Suitable inhibitors include peptide trifluoromethyul ketones, peptide boronic acids, peptide alpha-ketoesters, peptide difluoroketo compounds, peptide aldehydes, peptide diketones, and the like. For example, the peptide aldehyde N-acetyl-phelnylalanylglycinaldehyde is a potent inhibitor of the protease papain. One may conveniently prepare and assay large mixtures of peptides using the methods disclosed in PCT W089/10931, incorporated herein by reference. This application teaches methods for generating mixtures of peptides up to hexapeptides having all possible amino acid sequences, and further teaches assay methods for identifying those peptides capable of binding to proteases.

Other protease inhibitors may be proteins, particularly antibodies and antibody derivatives. Recombinant expression systems may be used to generate quantities of protease sufficient for production of monoclonal antibodies (MAbs) specific for the protease. Suitable antibodies for protease inhibition will bind to the protease in a manner reducing or eliminating the enzymatic activity, typically by obscuring the active site. Suitable MAbs may be used to generate derivatives such as Fab fragments, chimeric antibodies, altered antibodies, univalent antibodies, and single domain antibodies, using methods known in the art.

Protease inhibitors are screened using methods of the invention, in general, a substrate is employed which mimics the enzyme's natural substrate, but which provides a quantifiable signal when cleaved. The signal is preferably detectable by colorimetric or fluorimetric means: however, other methods such as HPLC or silica gel chromatography, GC-MS, nuclear magnetic resonance, and the like may also be useful. After optimum substrate and enzyme concentrations are determined, a candidate protease inhibitor is added to the reaction mixture at a range of concentrations The assay condition ideally should resemble the conditions under which the protease is to be inhibited in-vivo; i.e., under physiologic pH, temperature, ionic strength, etc. Suitable inhibitors will exhibit strong protease inhibition at concentrations which do not raise toxic side effects in the subject. Inhibitors which compete for binding to the protease active site may require concentrations equal to or greater than the substrate concentration, while inhibitors capable of binding irreversibly to the protease active site may be added in concentrations on the order of the enzyme concentration.

In a presently preferred embodiment, a reporter gene is placed very near (i.e., within 50 amino acids), and carboxy to, the NS3/NS4A-B cleavage site, in a vector containing NS2B, NS3 and about 50 amino acids of NS4A-B. A prospective protease inhibitor is added to the cell culture prior to infection with this vector. By structuring the reporter gene very near the cleavage site, the reporter gene will carry a small amino terminal addition of less than about 50 amino acids. In the preferred embodiment this small addition will allow natural folding of the reporter gene and will not compromise its activity. However, if the protease is inactivated the reporter gene will have more than seven hundred additional N-terminal amino acids conformationally destroying activity of the chosen reporter gene. Activity of the inhibitor can be further specifically quantified by separating insoluble fraction (containing the insoluble NS3-uncleaved reporter) from the soluble fraction containing cleaved reporter, for example, by the method of Example 4.

In another presently preferred embodiment, an inactive protease mutant is employed rather than an active enzyme. By replacing a critical residue within the active site of the protease (e.g., replacing the active site Ser of a serine protease) does not significantly alter the structure of the enzyme, and thus preserves the binding specificity. The altered enzyme still recognizes and binds to its proper substrate, but fails to effect cleavage. Thus, in one method of the invention an inactivated HGV protease is immobilized, and a mixture of candidate inhibitors added.

Inhibitors that closely mimic the enzyme's preferred recognition sequence will compete more successfully for binding than other candidate inhibitors. The poorly-binding candidates may then be separated, and the identity of the strongly-binding inhibitors determined. For example, HGV protease may be prepared substituting the native Ser.sub.1062 with Ala, providing an enzyme capable of binding the HGV protease substrate, but incapable of cleaving it. The resulting protease mutant is the bound to a solid support, for example Sephadex beads, and packed into a column. A mixture of candidate protease inhibitors in solution is then passed through the column and fractions collected. The last fraction to elute will contain the strongest-binding compounds and provide the preferred protease inhibitor candidates.

Protease inhibitors may be administered by a variety of methods, such as intravenously, orally, intramuscularly, introperitoneally, bronchially, intranasally, and so forth. The preferred route of administration will depend upon the nature of the inhibitor. Inhibitors prepared as organic compounds may often be administered orally (which is generally preferred) if well absorbed. Protein-based inhibitors (such as most antibody derivates) must generally be administered by parenteral routes.

HGV antigens encoded by non-structural genes which emulate those created during the natural course of infection comprise another aspect of the present invention. Such antigens are structurally and conformationally superior to those made by other processes as antibodies contained in HGV-infected human serum are more likely to recognize common conformational epitopes. Such antigens may be produced by the method of the present invention as follows: Cells are co-infected with a first virus expressing an HGV protease and a second virus expressing HGV substrate including at least one entire gene of interest and its flanking sequences containing cleavage sites at either, or both ends.

The NS2A/NS2B, NS2B/NS3, and NS4A-B/NS5A cleavage sites have been determined experimentally, according to the method of Example 7. According to the present invention, the following are the determined, and predicted, sequences of the HGV genes. NS2B is shown as SEQ ID NO:32, NS3 is shown as SEQ ID NO:34, NS4A-B as SEQ ID NO:36, NS5A as SEQ ID NO:38, and NS5B as SEQ ID NO:40. Accordingly, in the method of producing HGV antigens, the above enumerated sequences should be expressed plus as much additional flanking sequences on both the amino and carboxy termini as possible without compromising expression, as is known to those of ordinary skill in the art is and vector/host dependent.

HGV polypeptides made by the present invention can be purified directly or produced recombinantly and then purified. The recombinant polypeptides of the present invention can be purified by standard protein purification procedures which may include differential precipitation, molecular sieve chromatography, ion-exchange chromatography, isoelectric focusing, gel electrophoresis and affinity chromatography. The antigens can then be screened rapidly against a large number of suspected HGV hepatitis sera using alternative immunoassays, such as, ELISAs or Protein Blot Assays (Western blots) employing the isolated antigen peptide. The antigen polypeptides fusion can be isolated as described above, usually by affinity chromatography to the fusion partner such as .beta.-galactosidase or glutathione-S-transferase. Alternatively, the antigen itself can be purified using antibodies generated against it (see below).

The purified antigen polypeptide or fusion polypeptide containing the antigen of interest, is attached to a solid support, for example, a multi-well polystyrene plate. Sera to be tested are diluted and added to the wells. After a period of time sufficient for the binding of antibodies to the bound antigens, the sera are washed out of the wells. A labelled reporter antibody is added to each well along with an appropriate substrate: wells containing antibodies bound to the purified antigen polypeptide or fusion polypeptide containing the antigen are detected by a positive signal.

A typical format for protein blot analysis using the polypeptide antigens of the present invention is presented in Example 5. General protein blotting methods are described by Ausubel, F. M., et al., CURRENT PROTOCOLS IN MOLECUA BIOLOGY, John Wiley and Sons, Inc., Media Pa.

One utility for the antigens obtained by the methods of the present invention is their use as diagnostic reagents for the detection of antibodies present in the sera of test subjects infected with HGV hepatitis virus, thereby indicating infection in the subject. The antigens of the present invention can be used singly, or in combination with each other, in order to detect HGV. The antigens of the present invention may also be coupled with diagnostic assays for other hepatitis agents such as HAV, HBV, HCV, and HEV.

In one diagnostic configuration, test serum is reacted with a solid phase reagent having a surface-bound antigen obtained by the methods of the present invention, e.g., the NS5A antigen. After binding with anti-HGV antibody to the reagent and removing unbound serum components by washing, the reagent is reacted with reporter-labelled anti-human antibody to bind reporter to the reagent in proportion to the amount of bound anti-HGV antibody on the solid support. The reagent is again washed to remove unbound labelled antibody, and the amount of reporter associated with the reagent is determined. Typically, the reporter is an enzyme which is detected by incubating the solid phase in the presence of a suitable fluorometric or calorimetric substrate (Sigma, St. Louis, Mo.).

The solid surface reagent in the above assay is prepared by known techniques for attaching protein material to solid support material, such as polymeric beads, dip sticks, 96-well plate or filter material. These attachment methods generally include non-specific adsorption of the protein to the support or covalent attachment of the protein, typically through a free amine group, to a chemically reactive group on the solid support, such as an activated carboxyl, hydroxyl, or aldehyde group.

Also forming part of the invention is an assay system or kit for carrying out this diagnostic method. The kit generally includes a support with surface-bound recombinant HGV antigen (e.g., the NS5A antigen, as above), and a reporter-labelled anti-human antibody for detecting surface-bound anti-HGV antigen antibody.

In a second diagnostic configuration, known as a homogeneous assay, antibody binding to a solid support produces some change in the reaction medium which can be directly detected in the medium. Known general types of homogeneous assays proposed heretofore include (a) spin-labelled reporters, where antibody binding to the antigen is detected by a change in reported mobility (broadening of the spin splitting peaks), (b) fluorescent reporters, where binding is detected by a change in fluorescence efficiency or polarization, (c) enzyme reporters, where antibody binding causes enzyme/substrate interactions, and (d) liposome-bound reporters, where binding leads to liposome lysis and release of encapsulated reporter. The adaptation of these methods to the protein antigen of the present invention follows conventional methods for preparing homogeneous assay reagents.

In each of the assays described above, the assay method involves reacting the serum from a test individual with the protein antigen and examining the antigen for the presence of bound antibody. The examining may involve attaching a labelled anti-human antibody to the antibody being examined (for example from acute, chronic or convalescent phase) and measuring the amount of reporter bound to the solid support, as in the first method, or may involve observing the effect of antibody binding on a homogeneous assay reagent, as in the second method.

A third diagnostic configuration involves use of HGV antibodies capable of detecting HGV-specific antigens. The HGV antigens may be detected, for example, using an antigen capture assay where HGV antigens present in candidate serum samples are reacted with a HGV specific monoclonal or polyclonal antibody. The antibody is bound to a solid substrate and the antigen is then detected by a second, different labelled anti-HGV antibody. Antibodies can be prepared, utilizing the peptides of the present invention, by standard methods. Further, substantially isolated antibodies (essentially free of serum proteins which may affect reactivity) can be generated (e.g., affinity purification).

The following examples, which illustrate various methods and compositions in the invention, are intended to illustrate, but not limit the scope of the invention.

Materials

E. coli DNA polymerase I (Klenow fragment) can be obtained from Boehringer Mannheim Biochemicals (BMB) (Indianapolis, Ind.). T4 DNA ligase and T4 DNA polymerase may be obtained from New England Biolabs (Beverly, Mass.); Nitrocellulose and "NYTRAN" filters are obtainable from Schleicher and Schuell (Keene, N.H.).

Synthetic oligonucleotide linkers and primers may be prepared using commercially available automated oligonucleotide synthesizers. Alternatively, custom designed synthetic oligonucleotides may be purchased from commercial suppliers. cDNA synthesis kit and random priming labeling kits may be obtained from BMB (Indianapolis, Ind.) or GIBCO/BRL (Gaithersburg, Md.).

Common manipulations relevant to employing antisera and/or antibodies for screening and detection of immunoreactive protein antigens were performed essentially as described (Harlow, E., et al., ANTIBODIES: A LABORATORY MANUAL, Cold Spring Harbor Laboratory Press (1988), incorporated herein by reference).

A cDNA-insert phage library generated from serum sample PNF 2161 produced as described in PCT US95/06169, now published, was deposited with the American Type Culture Collection, 12301 Parklawn Dr., Rockville Md. 20852, and has been assigned the deposit designation ATCC 75268 (PNF 2161 cDNA source). This library was used to generate a plasmid, "p3ZHGV-6", which contains the complete ORF from the PNF-2161 genome (SEQ ID NO:1). p3ZHGV-6 is deposited at Genelabs Technologies, Inc., 505 Penobscot Drive, Redwood City, Calif., 94063.

Baculovirus transfer vectors pAcGl and pAcG3X are used for the expression of HGV proteins as fusions with glutathione-S-transferase (GST). Such vectors can be purchased from PharMingen (San Diego, Calif.). These vectors utilize a strong very-late baculovirus polyhedrin promoter enabling high expression levels. Further, the vectors are flexible allowing foreign genes to be placed downstream of the GST fusion in different open reading frames.

a. Recombinant Protease Construct

A baculovirus plasmid transfer vector, encoding the hydrophilic portion of NS2B, NS3 and the amino-terminal portion of NS4 (SEQ ID NO:24) is constructed as follows: 2 ug plasmid p3ZHGV-6 is incubated with 10 U BglII, 10 U StuI, in 20 ul 10 mM Tris-HCl pH 8.0, 5 mM MgCl.sub.2, 100 mM NaCl for 1 hour at 37 degrees C. The BgIII-StuI fragment is purified by the GeneClean kit, purchased from Bio101, according to the manufacturers instructions (Bio101, Vista, Calif.). 2 ug pAcG3.times.vector is digested with 10 U BamHI in 20 ul of the above described buffer for 1 hour at 37.degree. degrees C. Plasmid DNA is also purified using the GeneClean kit. The vector is next digested with 10 U SmaI in 20 ul 33 mM Tris-acetate pH 7.9, 10 mM Mg acetate, 66 mM potassium acetate, 0.5 mM dithiothreitol (DTT), for 1 hour at 25 degrees C. The plasmid DNA is again purified with the Geneclean kit.

Plasmid and insert DNA are mixed at a ratio of 1:10 and ligated with T4 ligase for overnight at 10 degrees C in 50 mM Tris-HCl pH 7.5, 7 mM MgCl.sub.2, 1 mM DTT, 1 mM ATP, 1 ug DNA, and 4 U enzyme. The ligation mixture is used to transform E. coli (Epicurian Coli XL1-Blue super competent cells, Stratagene, La Jolla, Calif.), according to the manufacturers instructions. Positive colonies are isolated and plasmids purified using Wizard.TM. minipreps DNA purification systems (Promega, Madison, Wis.). Purified plasmids are checked for correct inserts by BamHI/EcoRV restriction endonuclease cleavage and agarose gel analysis.

This vector will encode the Ile.sub.806 -Glu.sub.1658 portion of the HGV polyprotein in-frame with the GST. A recombinant baculovirus vector was constructed according to the method of the this example and designated "L. "

b. Recombinant Mutant Protease Constructs

Site-directed mutagenesis is utilized to generate transfer vectors which are ultimately used in studies to confirm particular active residues in NS2B and NS3. Point mutations are made by oligonucleotide-directed mutagenesis using uridylated phagemid DNA as the template and oligonucleotide primers with substitutions in codons specifying the amino acid to be changed; see T. Kunkel, Proc Nat Acad Sci (USA) (1985) 82:488. The particular primers shown below are used to generate the indicated changes: NO:42). NO:43).

c. Other Recombinant Baculovirus Vectors

Similar methods were used to construct other transfer vectors for HGV protease characterization. These vectors are briefly described here and summarized in Table 2, below.

Vector "G", FIG. 1, containing an insert encoding 31 carboxy-terminal amino acids of NS2B and all of NS3 (SEQ ID NO:51) can be synthesized by the polymerase chain reaction (PCR) utilizing primers "GF" and "GR", according to the method of Mullis, K. B., U.S. Pat. No. 4,683,202, issued 28 Jul. 1987; and Mullis, K. B., et al., U.S. Pat. No. 4,683,195, issued 28 Jul. 1987, both of which are herein incorporated by reference. Primer GF contains a BglII site and Primer GR contains an EcoRI site which facilitate the cloning of this fragment into the pAcG1 transfer vector in-frame with the coding sequence for the GST fusion partner. Vector G encodes an HGV polyprotein corresponding to Met.sub.895 to Arg.sub.1550, as shown in SEQ ID NO:2.

Vectors "42" and "23," FIG. 1, are carboxy-terminal truncations of the construct L in the NS4 region. Construct 42 (SEQ ID NO:52) can be produced by PCR using the primers 42F and 42R. Primer 42F flanks an internal SpeI site and primer 42R contains an EcoRI site. The fragment amplified with 42F and 42R, and cut with SpeI/EcoRI is ligated to the L vector cut with SpeI/EcoRI. Vector 42 encodes an HGV protein corresponding to amino acids Ile.sub.806 to Ala.sub.1598, as shown in SEQ ID NO:2.

Vector 23 (SEQ ID NO:53) can be produced by ligating the BglII-SpeI fragment of vector L to the SpeI-EcoRI fragment from vector G. Vector 23 encodes an HGV protein corresponding to Ile.sub.806 to Arg.sub.1550 as shown in SEQ ID NO:2.

Vector 4 (SEQ ID NO:54) can be produced by PCR using the 4F and 4R primers shown below and the p3ZHGV-6 plasmid as a template. The fragment is cut with BglII and EcoRI and cloned into the BamHI and EcoRI digested pAcGl transfer vector. Vector 4 encodes an HGV protein corresponding to amino acids Arg.sub.1540 to Lys.sub.1655 from SEQ ID NO:2.

Vector Q (SEQ ID NO:55), FIG. 1, encodes an HGV protein containing a carboxy-terminal portion of NS4 and amino-terminal portion of NS5A. p3ZHGV-6 was digested with HindIII and blunt ended with Klenow to make it compatible with the SmaI blunt ended cloning site of the pAcGl vector. p3ZHGV-6 is further digested with BglII resulting in a BglII/blunt-ended HindIII fragment which is ligated into pAcGl digested with BamHI/SmaI. Construct Q encodes a protein corresponding to amino acids Asp.sub.1806 to Lys.sub.2235, from SEQ ID NO:2.

Vector N (SEQ ID NO:56), FIG. 1, encodes an HGV protein containing the majority of NS5A and complete NS5B. p3ZHGV-6 was digested with Eco47.III and EcoRI, and ligated into pAcGl digested with EcoRI and SmaI. Construct N encodes a protein corresponding to amino acids Arg.sub.2078 to Gly.sub.2873 (carboxy terminus of the HGV polyprotein), as shown in SEQ ID NO:2. ______________________________________ Vector   Base Vector Insert       Mutations ______________________________________ L        pAcG3X     SEQ ID NO: 24 None LH       pAcG3X     SEQ ID NO: 26 His.sub.849 to Tyr LC       PAcG3X     SEQ ID NO: 28 Cys.sub.890 to Leu LS       PAcG3X     SEQ ID NO: 30 Ser.sub.1062 to Ala 42       pAcG3X     SEQ ID NO: 52 None 23       pAcG3X     SEQ ID NO: 53 None 4        pAcG1      SEQ ID NO: 54 None Q        pAcG1      SEQ ID NO: 55 None N        pAcG1      SEQ ID NO: 56 None G        pAcG1      SEQ ID NO: 51 None ______________________________________

Spodoptera frugiperda insect cell culture Sf21 and a derivative of Autografa californica nuclear polyhedrosis virus "BACULOGOLD" (PharMingen, San Diego, Calif.) are used for expression of HGV polypeptides. Established protocols are used for insect cell cultivation and for generation of recombinant baculoviruses by co-transfection of baculovirus plasmid transfer vectors with linearized baculovirus DNA (L. King et al, The baculovirus expression system. A laboratory guide, Chapman & Hall, London, New York, Tokyo, Melbourne, Madras, 1992). For convenience herein, the names of the transfer vectors produced above will be utilized to designate the corresponding recombinant baculovirus and expression products.

Briefly, the recombinant baculovirus plasmid transfer vector L can be co-trasnsfected with linearized baculovirus DNA ("BACULOGOLD") and the recombinant viruses selected as white foci in the presence of X-gal (King, supra). Monolayers of Sf21 cells are infected with the progeny of individual selected plaques and incubated at 27 degrees C. and harvested at 60 hours post infection. Cells are washed with phosphate buffered saline (PBS) and lysed in TNN buffer (50 mM Tris-HCl pH 8.0, 150 mM NaCl, 0.5% "NONIDET-P40").

The cell lysates are subject to centrifugation in a microfuge at 14,000 rpm for 10 minutes. Pellets (containing insoluble HGV proteins) and supernatant (containing soluble HGV proteins), together with a wild-type baculovirus-infected cell lysate (as control) are separated by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE). The expressed recombinant HGV proteins are identified as additional bands on the gel stained with Coomassie blue as compared with the wild-type lane.

It is beneficial to utilize purified HGV polypeptides produced according to the method of the present inventions. Several purification techniques are known in the art. Briefly, two such methods are describe below.

1. Affinity Chromatography

GST-HGV fusion proteins may be purified by glutathione-affinity chromatography according to the method described by A. H. Davies, Bio/technology, 11:993, incorporated herein by reference.

2. Partial Purification of Inclusion Bodies

The insoluble pellet obtained in the method of Example 6, is washed with 0.2M sodium phosphate pH 8.0-150 mM NaCl. The pellet is then sonicated for 5 min. in a Branson Sonier 450 sonicater set at output 6 at a 20 sec. cycle for 5 min. (so as not to causing excessive foaming or heating of the sample). The sonicated mixture is again subject to centrifugation in a microfuge at 14,000 rpm for 10 minutes. Both the soluble and insoluble fractions are taken and analyzed by SDS-PAGE for the presence of HGV proteins. Further extraction may be necessary as shown below if the HGV proteins are present in the insoluble fraction.

The pellet from above is solubilized in 100 mM Tris-HCl pH 8.0, 150 mM NaCl, 10 mM CHAPS (3-3-Cholamidopropyl)-dimethylammonio!-1-propane-sulfonate) (Sigma). The pellet is then sonicated for 5 min. in a Branson Sonier 450 sonicater set at output 6 at a 20 sec. cycle for 5 min. (so as not to causing excessive foaming or heating of the sample). The sonicated mixture is again subject to centrifugation in a microfuge at 14,000 rpm for 10 minutes. Both the soluble and insoluble fractions are taken and analyzed by SDS-PAGE for the presence of HGV proteins. Further extraction may be necessary and can be performed by methods known to those of skill in the art, essentially repeating the steps above with more aggressive buffers.

The recombinant HGV proteins produced according to the expression methodologies described herein can be further characterized by western blot analysis. The antigen from an SDS-PAGE gel run as above is transferred to a nitrocellulose filter. The membrane is then blocked for 2 hours using a solution of 1% bovine serum albumin, 3% normal goat serum, 0.25% gelatin, 100 mM NaPO.sub.4, 100 mM NaCl, and 1% nonfat dry milk. Following incubation the membrane is washed with Tris HCl, pH 7.5 and incubated with polyclonal rabbit anti-PEP4 (1:1,000) (see PCT US95/06169, Example 9, herein incorporated by reference for this HGV protein specific serum and others utilized herein) for 2 hrs. with rocking at room temperature.

The membrane is washed twice for three minutes each time in TBS plus "TWEEN 20" (0.05%), and then washed twice for five minutes each time in TBS. The membrane is then incubated with secondary antibody (Promega anti-rabbit IgG-Alkaline Phosphatase conjugate, 1:7,500), for 1 hour with rocking at room temperature. The membrane is then washed twice.times.5 minutes in TBS+"TWEEN 20", then twice.times.5 minutes in TBS.

Bound antibody is detected by incubating the membrane in a substrate solution containing 5-bromo-4-chloro-3-indolyl-phosphate (BCIP), and nitro blue tetrazolium salt (NBT) (Sigma) in pH 9.5 buffer (100 mM Tris, 100 mM NaCl, 5 mM MgCl.sub.2). Color development is allowed to proceed for approximately 15 minutes at which point color development is halted by 3 washes in distilled H.sub.2 O.

Construct L was expressed as a GST fusion in baculovirus. Insect cell extracts were run on an SDS-PAGE. It can be seen from FIG. 2, lane 5, that proteins migrate to sizes expected for NS3 and NS2B-GST indicating that the expressed protein is self-cleaved. Further, constructs LH, LC, and LS containing point mutations in the NS2B and NS3, as described in Example 2, are shown in FIG. 2, lanes 3, 2, and 4, respectively. It is apparent that the His to Tyr and Cys to Leu mutations in NS2B result in the loss of cleavage at the NS2B/NS3 junction, as demonstrated by the presence of the high molecular weight band migrating at the size expected for GST-NS2B-NS3. Furthermore, the loss of activity appears to be complete as there is virtually no GST-NS2B or NS3 products present in these lanes. The Ser to Ala mutation in construct LS, also described in Example 2, has no effect on cleavage at the NS2B/NS3 junction, demonstrated by the large amount of GST-NS2B present in lane 4. LS was unable to cleave at the NS3/NS4A-B junction, however, demonstrated by the large amount of protein migrating to the expected size for NS3-NS4-truncate. Identity of these proteins was further confirmed using anti-NS2B, NS3 and GST polyclonal rabbit antisera (rabbit sera described in PCT application US95/06169, Example 9, now published, GST monoclonal antibodies commercially available, for example, from Sierra Biosource, Gilroy, CA) results not shown.

The HGV protease activity was further characterized by co-infection of insect cells by two (or more) of the baculovirus recombinant vectors described in Example 2. The results of these experiments are summarized in Table 3, below. Co-infections can easily be performed by those of skill in the art. Such co-infections contain at least one HGV protease construct, which may or may not, include a point mutation. By way of example, co-infection experiments may be performed as is described below for the co-infection of Vector L and Vector N.

Semi-confluent monolayers of Sf21 cells are grown in 150 cm.sup.2 tissue culture flasks in TC-100 medium, prepared according to the manufacturers instructions (GIBCO-BRL, Bethesda, Md.) and supplemented with 10% fetal calf serum (FCS) (Gemini, Calabasas, Calif.). The medium is discarded and monolayers are either: (a) co-infected with recombinant baculovirus L and N at a multiplicity of infection (m.o.i.) of 2 and 10, respectively; (b) infected with recombinant baculovirus L, at an m.o.i. of 2; (c) infected with recombinant baculovirus N, at an m.o.i. of 10; or (d) wild-type baculovirus, at an m.o.i. of 10. Adsorbsion of viruses was allowed to proceed at room temperature for 1 hour on a slow rocker. 30 ml of fresh TC-100/10% FCS is added to the tissue culture flask and incubation continues at 27 degrees C. At 60 hours post-infection, monolayers were washed with PBS and lysed with TNN buffer according to the procedure describe in Example 3.

Soluble and insoluble fractions can be separated and compared for the presence of HGV proteins according to the method of Example 4. The soluble fraction is further purified using the Glutathione-Sepharose 4B (Pharmacia, Uppsala, Sweden), according to the method of Example 5.

The purified HGV proteins from each experiment (a)-(d), above, were analyzed by 12% SDS-PAGE. The results are shown in FIG. 3, and summarized in Table 3. ______________________________________ Insert     Site 1 Site 2     Site 3* Site 4* ______________________________________ L          +      +          +     + LH         -      +          +     + LC         -      +          +     + LS         +      -          -     - 42         +      +          +     + 23         +      ND         -     + 23 + 4     +      ND         +     + G          -      ND         ND    ND ______________________________________ Site 1 is the cleavage site between NS2B and NS3. Site 2 is the cleavage site between NS3 and NS4AB. Site 3 is the cleavage site between NS4AB and NS5A. Site 4 is the cleavage site between NS5A and NS5B. *Studies conducted for Site 3 all included insect cells coinfected with a first vector having the insert shown in the first column and with a secon vector having the insert Q described in Example 2. Likewise, studies conducted for Site 4 all included insect cells coinfected with a first vector having the insert shown in the first column and a second vector having the insert N described in Example 2.

The results summarized in Table 4 indicate that cleavage at the NS2B/NS3 junction (Site 1) occurs in cis. For example, Vector L is autocatalytic (FIG. 3, lane 5). Furthermore, the results indicate that such cleavage requires the presence of the carboxy terminal portion of NS2B. For example, the failure of constructs LH and LC to cleave at Site 1 (FIG. 3, Lanes 2 and 3) indicate the vital importance of His.sub.849 and Cys.sub.890 for function of NS2B. Further evidence of the importance of His.sub.849 and Cys.sub.890 as part of the NS2B catalytic domain is shown by the inability of Vector G (which does not include His.sub.849 and Cys.sub.890) to cleave at the NS2B/NS3 junction.

In contrast NS2B does not appear to be critical to cleavage at the NS3/NS4A-B junction (Site 2) as the point mutations in constructs LH and LC do not affect cleavage in cis. Construct LS, however, which is unable to cleave at the NS3/NS4A-B junction (FIG. 3, Lane 4) indicates the vital importance of the Ser.sub.1062 residue of NS3.

Cleavage at the NS4/NS5A junction (Site 3) is shown to occur in trans and require the presence of NS3 and the amino terminal portion of NS4A-B. From FIG. 4 it can be seen that the Q construct is cleaved when co-infected with L, 42, LH, and LC, lanes 3, 4, 5, and 6, respectively. However, where the critical Serine residue is absent, in the LS construct, no cleavage is observed with the Q substrate.

Co-infections of vector Q with vector 23 (FIG. 4, lane 8) failed to effect cleavage at the NS4/NS5A junction, however, when Q, 23 and 4 were co-infected cleavage at Site 3 is observed. This indicates the requirement of an NS4 co-factor supplied in trans by vector 4.

Similar results as with vector Q are seen with vector N demonstrating that cleavage at Site 4 (NS5A/NS5B) occurs in trans and is NS3 dependent (see FIG. 5). However, vector 23 co-infected with vector N was able to produce a cleavage event at Site 4 indicating that the NS4 co-factor is not obligatory for cleavage at this site.

Various regions of the HGV genome were integrated in to vaccinia virus genome for expression (see Example 16, PCT patent application US95/06169, now published), herein incorporated by reference. Vector 14 described therein can be utilized below for determination of the HGV polyprotein cleavage sites as this full-length polypeptide, which encodes the HGV protease functions, should be processed naturally as it is during the normal course of infection. The amino acid sequence of the N-terminus of each protein is deduced as described in J. Virol (1993), 67:2832-2843, briefly as follows.

BS-C-1 cells (1.times.10 ), available from the ATCC, infected with a recombinant vaccinia virus expressing full length HGV polyprotein at an m.o.i. of 10 pfu/cell are incubated with 5 ml Valine, Methionine, and Cysteine-free medium supplemented with .sup.3 H-Valine (200 uci/ml), .sup.35 S- Methionine, and/or .sup.35 S-Cysteine (50 uci/ml) for 2 hr. The cells are harvested and lysed according to known techniques.

The cell lysates are incubated with protein-A Sepharose beads preincubated (1 hr.) with rabbit polyclonal anti-HGV antiserum, described above. The samples are incubated for 4 hr. at 4 degrees C. The samples are then washed with buffers containing mild detergent known to those of skill in the art. The beads are collected by centrifugation and denatured in protein denaturation buffer containing 2% SDS, and heated at 100 degrees C for 10 min. The supernatant is loaded on an SDS-polyacrylamide gel. After electrophoresis, the proteins on the gel are transferred to PVDF membrane by a standard western blot technique.

The PVDF membrane is exposed to X-ray film and the region(s) containing radioactive bands are cut out and subject to N-terminal protein sequence analysis by Edman Degradation. Typically 20 cycles are carried out.

The radioactivity profiles for labelled amino acid (or combination thereof) is determined by scintillation counting from each cycle of sequence reactions and the .sup.3 H-Valine, .sup.35 S-Methionine and .sup.35 S-Cysteine profiles from sequencing reactions are compared to the predicted HGV sequence deduced from the isolated nucleic acid to map the amino termini for each HGV protein.

Experiments conducted according to the above method were performed and resulted in the identification of the following cleavage junctions: NS2A/NS2B, NS2B/NS3, and NS4/NS5A. These sites are incorporated with predicted site based on sequence homology with other flaviviruses to form three HGV proteins NS2B (SEQ ID NO:33), NS3 (SEQ ID NO:35), and NS4A-B (SEQ ID NO:37).

It is to be emphasized that the terms and descriptions used herein are preferred embodiments set forth by way of illustration only, and are not intended as limitations on the many variations which those of skill in the art will recognize to be possible in practicing the invention. Modifications and other uses will occur to those skilled in the art which are encompassed within the spirit of the invention or defined by the scope of the following claims. SEQUENCE LISTING (1) GENERAL INFORMATION: (iii) NUMBER OF SEQUENCES: 56 (2) INFORMATION FOR SEQ ID NO:1: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 9391 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: double (D) TOPOLOGY: linear (ii) MOLECULE TYPE: cDNA (vi) ORIGINAL SOURCE: (C) INDIVIDUAL ISOLATE: PNF-2161 genome (ix) FEATURE: (A) NAME/KEY: CDS (B) LOCATION: 459..9077 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:1: ACGTGGGGGAGTTGATCCCCCCCCCCCGGCACTGGGTGCAAGCCCCAGAAACCGACGCCT60 ATCTAAGTAGACGCAATGACTCGGCGCCGACTCGGCGACCGGCCAAAAGGTGGTGGATGG120 GTGATGACAGGGTTGGTAGGTCGTAAATCCCGGTCACCTTGGTAGCCACTATAGGTGGGT180 CTTAAGAGAAGGTTAAGATTCCTCTTGTGCCTGCGGCGAGACCGCGCACGGTCCACAGGT240 GTTGGCCCTACCGGTGGGAATAAGGGCCCGACGTCAGGCTCGTCGTTAAACCGAGCCCGT300 TACCCACCTGGGCAAACGACGCCCACGTACGGTCCACGTCGCCCTTCAATGTCTCTCTTG360 ACCAATAGGCGTAGCCGGCGAGTTGACAAGGACCAGTGGGGGCCGGGGGCTTGGAGAGGG420 ACTCCAAGTCCCGCCCTTCCCGGTGGGCCGGGAAATGCATGGGGCCACCCAGC473 MetGlyProProSer 15 TCCGCGGCGGCCTGCAGCCGGGGTAGCCCAAGAATCCTTCGGGTGAGG521 SerAlaAlaAlaCysSerArgGlySerProArgIleLeuArgValArg 101520 GCGGGTGGCATTTCCTTTTTCTATACCATCATGGCAGTCCTTCTGCTC569 AlaGlyGlyIleSerPhePheTyrThrIleMetAlaValLeuLeuLeu 253035 CTTCTCGTGGTTGAGGCCGGGGCCATTCTGGCCCCGGCCACCCACGCT617 LeuLeuValValGluAlaGlyAlaIleLeuAlaProAlaThrHisAla 404550 TGTCGAGCGAATGGGCAATATTTCCTCACAAATTGTTGTGCCCCGGAG665 CysArgAlaAsnGlyGlnTyrPheLeuThrAsnCysCysAlaProGlu 556065 GACATCGGGTTCTGCCTGGAGGGTGGATGCCTGGTGGCCCTGGGGTGC713 AspIleGlyPheCysLeuGluGlyGlyCysLeuValAlaLeuGlyCys 70758085 ACGATTTGCACTGACCAATGCTGGCCACTGTATCAGGCGGGTTTGGCT761 ThrIleCysThrAspGlnCysTrpProLeuTyrGlnAlaGlyLeuAla 9095100 GTGCGGCCTGGCAAGTCCGCGGCCCAACTGGTGGGGGAGCTGGGTAGC809 ValArgProGlyLysSerAlaAlaGlnLeuValGlyGluLeuGlySer 105110115 CTATACGGGCCCCTGTCGGTCTCGGCCTATGTGGCTGGGATCCTGGGC857 LeuTyrGlyProLeuSerValSerAlaTyrValAlaGlyIleLeuGly 120125130 CTGGGTGAGGTGTACTCGGGTGTCCTAACGGTGGGAGTCGCGTTGACG905 LeuGlyGluValTyrSerGlyValLeuThrValGlyValAlaLeuThr 135140145 CGCCGGGTCTACCCGGTGCCTAACCTGACGTGTGCAGTCGCGTGTGAG953 ArgArgValTyrProValProAsnLeuThrCysAlaValAlaCysGlu 150155160165 CTAAAGTGGGAAAGTGAGTTTTGGAGATGGACTGAACAGCTGGCCTCC1001 LeuLysTrpGluSerGluPheTrpArgTrpThrGluGlnLeuAlaSer 170175180 AACTACTGGATTCTGGAATACCTCTGGAAGGTCCCATTTGATTTCTGG1049 AsnTyrTrpIleLeuGluTyrLeuTrpLysValProPheAspPheTrp 185190195 AGAGGCGTGATAAGCCTGACCCCCTTGTTGGTTTGCGTGGCCGCATTG1097 ArgGlyValIleSerLeuThrProLeuLeuValCysValAlaAlaLeu 200205210 CTGCTGCTTGAGCAACGGATTGTCATGGTCTTCCTGTTGGTGACGATG1145 LeuLeuLeuGluGlnArgIleValMetValPheLeuLeuValThrMet 215220225 GCCGGGATGTCGCAAGGCGCCCCTGCCTCCGTTTTGGGGTCACGCCCC1193 AlaGlyMetSerGlnGlyAlaProAlaSerValLeuGlySerArgPro 230235240245 TTTGACTACGGGTTGACTTGGCAGACCTGCTCTTGCAGGGCCAACGGT1241 PheAspTyrGlyLeuThrTrpGlnThrCysSerCysArgAlaAsnGly 250255260 TCGCGTTTTTCGACTGGGGAGAAGGTGTGGGACCGTGGGAACGTTACG1289 SerArgPheSerThrGlyGluLysValTrpAspArgGlyAsnValThr 265270275 CTTCAGTGTGACTGCCCTAACGGCCCCTGGGTGTGGTTGCCAGCCTTT1337 LeuGlnCysAspCysProAsnGlyProTrpValTrpLeuProAlaPhe 280285290 TGCCAAGCAATCGGCTGGGGTGACCCCATCACTTATTGGAGCCACGGG1385 CysGlnAlaIleGlyTrpGlyAspProIleThrTyrTrpSerHisGly 295300305 CAAAATCAGTGGCCCCTTTCATGCCCCCAGTATGTCTATGGGTCTGCT1433 GlnAsnGlnTrpProLeuSerCysProGlnTyrValTyrGlySerAla 310315320325 ACAGTCACTTGCGTGTGGGGTTCCGCTTCTTGGTTTGCCTCCACCAGT1481 ThrValThrCysValTrpGlySerAlaSerTrpPheAlaSerThrSer 330335340 GGTCGCGACTCGAAGATAGATGTGTGGAGTTTAGTGCCAGTTGGCTCT1529 GlyArgAspSerLysIleAspValTrpSerLeuValProValGlySer 345350355 GCCACCTGCACCATAGCCGCACTTGGATCATCGGATCGCGACACGGTG1577 AlaThrCysThrIleAlaAlaLeuGlySerSerAspArgAspThrVal 360365370 CCTGGGCTCTCCGAGTGGGGAATCCCGTGCGTGACGTGTGTTCTGGAC1625 ProGlyLeuSerGluTrpGlyIleProCysValThrCysValLeuAsp 375380385 CGTCGGCCTGCCTCCTGCGGCACCTGTGTGAGGGACTGCTGGCCCGAG1673 ArgArgProAlaSerCysGlyThrCysValArgAspCysTrpProGlu 390395400405 ACCGGGTCGGTTAGGTTCCCATTCCATCGGTGCGGCGTGGGGCCTCGG1721 ThrGlySerValArgPheProPheHisArgCysGlyValGlyProArg 410415420 CTGACAAAGGACTTGGAAGCTGTGCCCTTCGTCAACAGGACAACTCCC1769 LeuThrLysAspLeuGluAlaValProPheValAsnArgThrThrPro 425430435 TTCACCATTAGGGGGCCCCTGGGCAACCAGGGCCGAGGCAACCCGGTG1817 PheThrIleArgGlyProLeuGlyAsnGlnGlyArgGlyAsnProVal 440445450 CGGTCGCCCTTGGGTTTTGGGTCCTACGCCATGACCAGGATCCGAGAT1865 ArgSerProLeuGlyPheGlySerTyrAlaMetThrArgIleArgAsp 455460465 ACCCTACATCTGGTGGAGTGTCCCACACCAGCCATTGAGCCTCCCACC1913 ThrLeuHisLeuValGluCysProThrProAlaIleGluProProThr 470475480485 GGGACGTTTGGGTTCTTCCCCGGGACGCCGCCTCTCAACAACTGCATG1961 GlyThrPheGlyPhePheProGlyThrProProLeuAsnAsnCysMet 490495500 CTCTTGGGCACGGAAGTGTCCGAGGCACTTGGGGGGGCTGGCCTCACG2009 LeuLeuGlyThrGluValSerGluAlaLeuGlyGlyAlaGlyLeuThr 505510515 GGGGGGTTCTATGAACCCCTGGTGCGCAGGTGTTCGAAGCTGATGGGA2057 GlyGlyPheTyrGluProLeuValArgArgCysSerLysLeuMetGly 520525530 AGCCGAAATCCGGTTTGTCCGGGGTTTGCATGGCTCTCTTCGGGCAGG2105 SerArgAsnProValCysProGlyPheAlaTrpLeuSerSerGlyArg 535540545 CCTGATGGGTTTATACATGTCCAGGGTCACTTGCAGGAGGTGGATGCA2153 ProAspGlyPheIleHisValGlnGlyHisLeuGlnGluValAspAla 550555560565 GGCAACTTCATCCCGCCCCCGCGCTGGTTGCTCTTGGACTTTGTATTT2201 GlyAsnPheIleProProProArgTrpLeuLeuLeuAspPheValPhe 570575580 GTCCTGTTATACCTGATGAAGCTGGCTGAGGCACGGTTGGTCCCGCTG2249 ValLeuLeuTyrLeuMetLysLeuAlaGluAlaArgLeuValProLeu 585590595 ATCTTGCTGCTGCTATGGTGGTGGGTGAACCAGCTGGCAGTCCTAGGG2297 IleLeuLeuLeuLeuTrpTrpTrpValAsnGlnLeuAlaValLeuGly 600605610 CTGCCGGCTGTGGAAGCCGCCGTGGCAGGTGAGGTCTTCGCGGGCCCT2345 LeuProAlaValGluAlaAlaValAlaGlyGluValPheAlaGlyPro 615620625 GCCCTGTCCTGGTGTCTGGGACTCCCGGTCGTCAGTATGATATTGGGT2393 AlaLeuSerTrpCysLeuGlyLeuProValValSerMetIleLeuGly 630635640645 TTGGCAAACCTGGTGCTGTACTTTAGATGGTTGGGACCCCAACGCCTG2441 LeuAlaAsnLeuValLeuTyrPheArgTrpLeuGlyProGlnArgLeu 650655660 ATGTTCCTCGTGTTGTGGAAGCTTGCTCGGGGAGCTTTCCCGCTGGCC2489 MetPheLeuValLeuTrpLysLeuAlaArgGlyAlaPheProLeuAla 665670675 CTCTTGATGGGGATTTCGGCGACCCGCGGGCGCACCTCAGTGCTCGGG2537 LeuLeuMetGlyIleSerAlaThrArgGlyArgThrSerValLeuGly 680685690 GCCGAGTTCTGCTTCGATGCTACATTCGAGGTGGACACTTCGGTGTTG2585 AlaGluPheCysPheAspAlaThrPheGluValAspThrSerValLeu 695700705 GGCTGGGTGGTGGCCAGTGTGGTAGCTTGGGCCATTGCGCTCCTGAGC2633 GlyTrpValValAlaSerValValAlaTrpAlaIleAlaLeuLeuSer 710715720725 TCGATGAGCGCAGGGGGGTGGAGGCACAAAGCCGTGATCTATAGGACG2681 SerMetSerAlaGlyGlyTrpArgHisLysAlaValIleTyrArgThr 730735740 TGGTGTAAGGGGTACCAGGCAATCCGTCAAAGGGTGGTGAGGAGCCCC2729 TrpCysLysGlyTyrGlnAlaIleArgGlnArgValValArgSerPro 745750755 CTCGGGGAGGGGCGGCCTGCCAAACCCCTGACCTTTGCCTGGTGCTTG2777 LeuGlyGluGlyArgProAlaLysProLeuThrPheAlaTrpCysLeu 760765770 GCCTCGTACATCTGGCCAGATGCTGTGATGATGGTGGTGGTTGCCTTG2825 AlaSerTyrIleTrpProAspAlaValMetMetValValValAlaLeu 775780785 GTCCTTCTCTTTGGCCTGTTCGACGCGTTGGATTGGGCCTTGGAGGAG2873 ValLeuLeuPheGlyLeuPheAspAlaLeuAspTrpAlaLeuGluGlu 790795800805 ATCTTGGTGTCCCGGCCCTCGTTGCGGCGTTTGGCTCGGGTGGTTGAG2921 IleLeuValSerArgProSerLeuArgArgLeuAlaArgValValGlu 810815820 TGCTGTGTGATGGCGGGTGAGAAGGCCACAACCGTCCGGCTGGTCTCC2969 CysCysValMetAlaGlyGluLysAlaThrThrValArgLeuValSer 825830835 AAGATGTGTGCGAGAGGAGCTTATTTGTTCGATCATATGGGCTCTTTT3017 LysMetCysAlaArgGlyAlaTyrLeuPheAspHisMetGlySerPhe 840845850 TCGCGTGCTGTCAAGGAGCGCCTGTTGGAATGGGACGCAGCTCTTGAA3065 SerArgAlaValLysGluArgLeuLeuGluTrpAspAlaAlaLeuGlu 855860865 CCTCTGTCATTCACTAGGACGGACTGTCGCATCATACGGGATGCCGCG3113 ProLeuSerPheThrArgThrAspCysArgIleIleArgAspAlaAla 870875880885 AGGACTTTGTCCTGCGGGCAGTGCGTCATGGGTTTACCCGTGGTTGCG3161 ArgThrLeuSerCysGlyGlnCysValMetGlyLeuProValValAla 890895900 CGCCGTGGTGATGAGGTTCTCATCGGCGTCTTCCAGGATGTGAATCAT3209 ArgArgGlyAspGluValLeuIleGlyValPheGlnAspValAsnHis 905910915 TTGCCTCCCGGGTTTGTTCCGACCGCGCCTGTTGTCATCCGACGGTGC3257 LeuProProGlyPheValProThrAlaProValValIleArgArgCys 920925930 GGAAAGGGCTTCTTGGGGGTCACAAAGGCTGCCTTGACAGGTCGGGAT3305 GlyLysGlyPheLeuGlyValThrLysAlaAlaLeuThrGlyArgAsp 935940945 CCTGACTTACATCCAGGGAACGTCATGGTGTTGGGGACGGCTACGTCG3353 ProAspLeuHisProGlyAsnValMetValLeuGlyThrAlaThrSer 950955960965 CGAAGCATGGGAACATGCTTGAACGGCCTGCTGTTCACGACCTTCCAT3401 ArgSerMetGlyThrCysLeuAsnGlyLeuLeuPheThrThrPheHis 970975980 GGGGCTTCATCCCGAACCATCGCCACACCCGTGGGGGCCCTTAATCCC3449 GlyAlaSerSerArgThrIleAlaThrProValGlyAlaLeuAsnPro 985990995 AGATGGTGGTCAGCCAGTGATGATGTCACGGTGTATCCACTCCCGGAT3497 ArgTrpTrpSerAlaSerAspAspValThrValTyrProLeuProAsp 100010051010 GGGGCTACTTCGTTAACACCTTGTACTTGCCAGGCTGAGTCCTGTTGG3545 GlyAlaThrSerLeuThrProCysThrCysGlnAlaGluSerCysTrp 101510201025 GTCATCAGATCCGACGGGGCCCTATGCCATGGCTTGAGCAAGGGGGAC3593 ValIleArgSerAspGlyAlaLeuCysHisGlyLeuSerLysGlyAsp 1030103510401045 AAGGTGGAGCTGGATGTGGCCATGGAGGTCTCTGACTTCCGTGGCTCG3641 LysValGluLeuAspValAlaMetGluValSerAspPheArgGlySer 105010551060 TCTGGCTCACCGGTCCTATGTGACGAAGGGCACGCAGTAGGAATGCTC3689 SerGlySerProValLeuCysAspGluGlyHisAlaValGlyMetLeu 106510701075 GTGTCTGTGCTTCACTCCGGTGGTAGGGTCACCGCGGCACGGTTCACT3737 ValSerValLeuHisSerGlyGlyArgValThrAlaAlaArgPheThr 108010851090 AGGCCGTGGACCCAAGTGCCAACAGATGCCAAAACCACTACTGAACCC3785 ArgProTrpThrGlnValProThrAspAlaLysThrThrThrGluPro 109511001105 CCTCCGGTGCCGGCCAAAGGAGTTTTCAAAGAGGCCCCGTTGTTTATG3833 ProProValProAlaLysGlyValPheLysGluAlaProLeuPheMet 1110111511201125 CCTACGGGAGCGGGAAAGAGCACTCGCGTCCCGTTGGAGTACGATAAC3881 ProThrGlyAlaGlyLysSerThrArgValProLeuGluTyrAspAsn 113011351140 ATGGGGCACAAGGTCTTAATCTTGAACCCCTCAGTGGCCACTGTGCGG3929 MetGlyHisLysValLeuIleLeuAsnProSerValAlaThrValArg 114511501155 GCCATGGGCCCGTACATGGAGCGGCTGGCGGGTAAACATCCAAGTATA3977 AlaMetGlyProTyrMetGluArgLeuAlaGlyLysHisProSerIle 116011651170 TACTGTGGGCATGATACAACTGCTTTCACAAGGATCACTGACTCCCCC4025 TyrCysGlyHisAspThrThrAlaPheThrArgIleThrAspSerPro 117511801185 CTGACGTATTCAACCTATGGGAGGTTTTTGGCCAACCCTAGGCAGATG4073 LeuThrTyrSerThrTyrGlyArgPheLeuAlaAsnProArgGlnMet 1190119512001205 CTACGGGGCGTTTCGGTGGTCATTTGTGATGAGTGCCACAGTCATGAC4121 LeuArgGlyValSerValValIleCysAspGluCysHisSerHisAsp 121012151220 TCAACCGTGCTGTTAGGCATTGGGAGAGTCCGGGAGCTGGCGCGTGGG4169 SerThrValLeuLeuGlyIleGlyArgValArgGluLeuAlaArgGly 122512301235 TGCGGGGTGCAACTAGTGCTCTACGCCACCGCTACACCTCCCGGATCC4217 CysGlyValGlnLeuValLeuTyrAlaThrAlaThrProProGlySer 124012451250 CCTATGACGCAGCACCCTTCCATAATTGAGACAAAATTGGACGTGGGC4265 ProMetThrGlnHisProSerIleIleGluThrLysLeuAspValGly 125512601265 GAGATTCCCTTTTATGGGCATGGAATACCCCTCGAGCGGATGCGAACC4313 GluIleProPheTyrGlyHisGlyIleProLeuGluArgMetArgThr 1270127512801285 GGAAGGCACCTCGTGTTCTGCCATTCTAAGGCTGAGTGCGAGCGCCTT4361 GlyArgHisLeuValPheCysHisSerLysAlaGluCysGluArgLeu 129012951300 GCTGGCCAGTTCTCCGCTAGGGGGGTCAATGCCATTGCCTATTATAGG4409 AlaGlyGlnPheSerAlaArgGlyValAsnAlaIleAlaTyrTyrArg 130513101315 GGTAAAGACAGTTCTATCATCAAGGATGGGGACCTGGTGGTCTGTGCT4457 GlyLysAspSerSerIleIleLysAspGlyAspLeuValValCysAla 132013251330 ACAGACGCGCTTTCCACTGGGTACACTGGAAATTTCGACTCCGTCACC4505 ThrAspAlaLeuSerThrGlyTyrThrGlyAsnPheAspSerValThr 133513401345 GACTGTGGATTAGTGGTGGAGGAGGTCGTTGAGGTGACCCTTGATCCC4553 AspCysGlyLeuValValGluGluValValGluValThrLeuAspPro 1350135513601365 ACCATTACCATCTCCCTGCGGACAGTGCCTGCGTCGGCTGAACTGTCG4601 ThrIleThrIleSerLeuArgThrValProAlaSerAlaGluLeuSer 137013751380 ATGCAAAGACGAGGACGCACGGGTAGGGGCAGGTCTGGACGCTACTAC4649 MetGlnArgArgGlyArgThrGlyArgGlyArgSerGlyArgTyrTyr 138513901395 TACGCGGGGGTGGGCAAAGCCCCTGCGGGTGTGGTGCGCTCAGGTCCT4697 TyrAlaGlyValGlyLysAlaProAlaGlyValValArgSerGlyPro 140014051410 GTCTGGTCGGCGGTGGAAGCTGGAGTGACCTGGTACGGAATGGAACCT4745 ValTrpSerAlaValGluAlaGlyValThrTrpTyrGlyMetGluPro 141514201425 GACTTGACAGCTAACCTACTGAGACTTTACGACGACTGCCCTTACACC4793 AspLeuThrAlaAsnLeuLeuArgLeuTyrAspAspCysProTyrThr 1430143514401445 GCAGCCGTCGCGGCTGATATCGGAGAAGCCGCGGTGTTCTTCTCTGGG4841 AlaAlaValAlaAlaAspIleGlyGluAlaAlaValPhePheSerGly 145014551460 CTCGCCCCATTGAGGATGCACCCTGATGTCAGCTGGGCAAAAGTTCGC4889 LeuAlaProLeuArgMetHisProAspValSerTrpAlaLysValArg 146514701475 GGCGTCAACTGGCCCCTCTTGGTGGGTGTTCAGCGGACCATGTGTCGG4937 GlyValAsnTrpProLeuLeuValGlyValGlnArgThrMetCysArg 148014851490 GAAACACTGTCTCCCGGCCCATCGGATGACCCCCAATGGGCAGGTCTG4985 GluThrLeuSerProGlyProSerAspAspProGlnTrpAlaGlyLeu 149515001505 AAGGGCCCAAATCCTGTCCCACTCCTGCTGAGGTGGGGCAATGATTTA5033 LysGlyProAsnProValProLeuLeuLeuArgTrpGlyAsnAspLeu 1510151515201525 CCATCTAAAGTGGCCGGCCACCACATAGTGGACGACCTGGTCCGGAGA5081 ProSerLysValAlaGlyHisHisIleValAspAspLeuValArgArg 153015351540 CTCGGTGTGGCGGAGGGTTACGTCCGCTGCGACGCTGGGCCGATCTTG5129 LeuGlyValAlaGluGlyTyrValArgCysAspAlaGlyProIleLeu 154515501555 ATGATCGGTCTAGCTATCGCGGGGGGAATGATCTACGCGTCATACACC5177 MetIleGlyLeuAlaIleAlaGlyGlyMetIleTyrAlaSerTyrThr 156015651570 GGGTCGCTAGTGGTGGTGACAGACTGGGATGTGAAGGGGGGTGGCGCC5225 GlySerLeuValValValThrAspTrpAspValLysGlyGlyGlyAla 157515801585 CCCCTTTATCGGCATGGAGACCAGGCCACGCCTCAGCCGGTGGTGCAG5273 ProLeuTyrArgHisGlyAspGlnAlaThrProGlnProValValGln 1590159516001605 GTTCCTCCGGTAGACCATCGGCCGGGGGGTGAATCAGCACCATCGGAT5321 ValProProValAspHisArgProGlyGlyGluSerAlaProSerAsp 161016151620 GCCAAGACAGTGACAGATGCGGTGGCAGCCATCCAGGTGGACTGCGAT5369 AlaLysThrValThrAspAlaValAlaAlaIleGlnValAspCysAsp 162516301635 TGGACTATCATGACTCTGTCGATCGGAGAAGTGTTGTCCTTGGCTCAG5417 TrpThrIleMetThrLeuSerIleGlyGluValLeuSerLeuAlaGln 164016451650 GCTAAGACGGCCGAGGCCTACACAGCAACCGCCAAGTGGCTCGCTGGC5465 AlaLysThrAlaGluAlaTyrThrAlaThrAlaLysTrpLeuAlaGly 165516601665 TGCTATACGGGGACGCGGGCCGTTCCCACTGTATCCATTGTTGACAAG5513 CysTyrThrGlyThrArgAlaValProThrValSerIleValAspLys 1670167516801685 CTCTTCGCCGGAGGGTGGGCGGCTGTGGTGGGCCATTGCCACAGCGTG5561 LeuPheAlaGlyGlyTrpAlaAlaValValGlyHisCysHisSerVal 169016951700 ATTGCTGCGGCGGTGGCGGCCTACGGGGCTTCAAGGAGCCCGCCGTTG5609 IleAlaAlaAlaValAlaAlaTyrGlyAlaSerArgSerProProLeu 170517101715 GCAGCCGCGGCTTCCTACCTGATGGGGTTGGGCGTTGGAGGCAACGCT5657 AlaAlaAlaAlaSerTyrLeuMetGlyLeuGlyValGlyGlyAsnAla 172017251730 CAGACGCGCCTGGCGTCTGCCCTCCTATTGGGGGCTGCTGGAACCGCC5705 GlnThrArgLeuAlaSerAlaLeuLeuLeuGlyAlaAlaGlyThrAla 173517401745 TTGGGCACTCCTGTCGTGGGCTTGACCATGGCAGGTGCGTTCATGGGG5753 LeuGlyThrProValValGlyLeuThrMetAlaGlyAlaPheMetGly 1750175517601765 GGGGCCAGTGTCTCCCCCTCCTTGGTCACCATTTTATTGGGGGCCGTC5801 GlyAlaSerValSerProSerLeuValThrIleLeuLeuGlyAlaVal 177017751780 GGAGGTTGGGAGGGTGTTGTCAACGCGGCGAGCCTAGTCTTTGACTTC5849 GlyGlyTrpGluGlyValValAsnAlaAlaSerLeuValPheAspPhe 178517901795 ATGGCGGGGAAACTTTCATCAGAAGATCTGTGGTATGCCATCCCGGTA5897 MetAlaGlyLysLeuSerSerGluAspLeuTrpTyrAlaIleProVal 180018051810 CTGACCAGCCCGGGGGCGGGCCTTGCGGGGATCGCTCTCGGGTTGGTT5945 LeuThrSerProGlyAlaGlyLeuAlaGlyIleAlaLeuGlyLeuVal 181518201825 TTGTATTCAGCTAACAACTCTGGCACTACCACTTGGTTGAACCGTCTG5993 LeuTyrSerAlaAsnAsnSerGlyThrThrThrTrpLeuAsnArgLeu 1830183518401845 CTGACTACGTTACCAAGGTCTTCATGTATCCCGGACAGTTACTTTCAG6041 LeuThrThrLeuProArgSerSerCysIleProAspSerTyrPheGln 185018551860 CAAGTTGACTATTGCGACAAGGTCTCAGCCGTGCTCCGGCGCCTGAGC6089 GlnValAspTyrCysAspLysValSerAlaValLeuArgArgLeuSer 186518701875 CTCACCCGCACAGTGGTTGCCCTGGTCAACAGGGAGCCTAAGGTGGAT6137 LeuThrArgThrValValAlaLeuValAsnArgGluProLysValAsp 188018851890 GAGGTACAGGTGGGGTATGTCTGGGACCTGTGGGAGTGGATCATGCGC6185 GluValGlnValGlyTyrValTrpAspLeuTrpGluTrpIleMetArg 189519001905 CAAGTGCGCGTGGTCATGGCCAGACTCAGGGCCCTCTGCCCCGTGGTG6233 GlnValArgValValMetAlaArgLeuArgAlaLeuCysProValVal 1910191519201925 TCACTACCCTTGTGGCATTGCGGGGAGGGGTGGTCCGGGGAATGGTTG6281 SerLeuProLeuTrpHisCysGlyGluGlyTrpSerGlyGluTrpLeu 193019351940 CTTGACGGTCATGTTGAGAGTCGCTGCCTCTGTGGCTGCGTGATCACT6329 LeuAspGlyHisValGluSerArgCysLeuCysGlyCysValIleThr 194519501955 GGTGACGTTCTGAATGGGCAACTCAAAGAACCAGTTTACTCTACCAAG6377 GlyAspValLeuAsnGlyGlnLeuLysGluProValTyrSerThrLys 196019651970 CTGTGCCGGCACTATTGGATGGGGACTGTCCCTGTGAACATGCTGGGT6425 LeuCysArgHisTyrTrpMetGlyThrValProValAsnMetLeuGly 197519801985 TACGGTGAAACGTCGCCTCTCCTGGCCTCCGACACCCCGAAGGTTGTG6473 TyrGlyGluThrSerProLeuLeuAlaSerAspThrProLysValVal 1990199520002005 CCCTTCGGGACGTCTGGCTGGGCTGAGGTGGTGGTGACCACTACCCAC6521 ProPheGlyThrSerGlyTrpAlaGluValValValThrThrThrHis 201020152020 GTGGTAATCAGGAGGACCTCCGCCTATAAGCTGCTGCGCCAGCAAATC6569 ValValIleArgArgThrSerAlaTyrLysLeuLeuArgGlnGlnIle 202520302035 CTATCGGCTGCTGTAGCTGAGCCCTACTACGTCGACGGCATTCCGGTC6617 LeuSerAlaAlaValAlaGluProTyrTyrValAspGlyIleProVal 204020452050 TCATGGGACGCGGACGCTCGTGCGCCCGCCATGGTCTATGGCCCTGGG6665 SerTrpAspAlaAspAlaArgAlaProAlaMetValTyrGlyProGly 205520602065 CAAAGTGTTACCATTGACGGGGAGCGCTACACCTTGCCTCATCAACTG6713 GlnSerValThrIleAspGlyGluArgTyrThrLeuProHisGlnLeu 2070207520802085 AGGCTCAGGAATGTGGCACCCTCTGAGGTTTCATCCGAGGTGTCCATT6761 ArgLeuArgAsnValAlaProSerGluValSerSerGluValSerIle 209020952100 GACATTGGGACGGAGACTGAAGACTCAGAACTGACTGAGGCCGATCTG6809 AspIleGlyThrGluThrGluAspSerGluLeuThrGluAlaAspLeu 210521102115 CCGCCGGCGGCTGCTGCTCTCCAAGCGATCGAGAATGCTGCGAGGATT6857 ProProAlaAlaAlaAlaLeuGlnAlaIleGluAsnAlaAlaArgIle 212021252130 CTTGAACCGCACATTGATGTCATCATGGAGGACTGCAGTACACCCTCT6905 LeuGluProHisIleAspValIleMetGluAspCysSerThrProSer 213521402145 CTTTGTGGTAGTAGCCGAGAGATGCCTGTATGGGGAGAAGACATCCCC6953 LeuCysGlySerSerArgGluMetProValTrpGlyGluAspIlePro 2150215521602165 CGTACTCCATCGCCAGCACTTATCTCGGTTACTGAGAGCAGCTCAGAT7001 ArgThrProSerProAlaLeuIleSerValThrGluSerSerSerAsp 217021752180 GAGAAGACCCCGTCGGTGTCCTCCTCGCAGGAGGATACCCCGTCCTCT7049 GluLysThrProSerValSerSerSerGlnGluAspThrProSerSer 218521902195 GACTCATTCGAGGTCATCCAAGAGTCCGAGACAGCCGAAGGGGAGGAA7097 AspSerPheGluValIleGlnGluSerGluThrAlaGluGlyGluGlu 220022052210 AGTGTCTTCAACGTGGCTCTTTCCGTATTAAAAGCCTTATTTCCACAG7145 SerValPheAsnValAlaLeuSerValLeuLysAlaLeuPheProGln 221522202225 AGCGACGCGACCAGGAAGCTTACCGTCAAGATGTCGTGCTGCGTTGAA7193 SerAspAlaThrArgLysLeuThrValLysMetSerCysCysValGlu 2230223522402245 AAGAGCGTCACGCGCTTTTTCTCATTGGGGTTGACGGTGGCTGATGTT7241 LysSerValThrArgPhePheSerLeuGlyLeuThrValAlaAspVal 225022552260 GCTAGCCTGTGTGAGATGGAAATCCAGAACCATACAGCCTATTGTGAC7289 AlaSerLeuCysGluMetGluIleGlnAsnHisThrAlaTyrCysAsp 226522702275 CAGGTGCGCACTCCGCTTGAATTGCAGGTTGGGTGCTTGGTGGGCAAT7337 GlnValArgThrProLeuGluLeuGlnValGlyCysLeuValGlyAsn 228022852290 GAACTTACCTTTGAATGTGACAAGTGTGAGGCTAGGCAAGAAACCTTG7385 GluLeuThrPheGluCysAspLysCysGluAlaArgGlnGluThrLeu 229523002305 GCCTCCTTCTCTTACATTTGGTCTGGAGTGCCGCTGACTAGGGCCACG7433 AlaSerPheSerTyrIleTrpSerGlyValProLeuThrArgAlaThr 2310231523202325 CCGGCCAAGCCTCCCGTGGTGAGGCCGGTTGGCTCTTTGTTAGTGGCC7481 ProAlaLysProProValValArgProValGlySerLeuLeuValAla 233023352340 GACACTACTAAGGTGTATGTTACCAATCCAGACAATGTGGGACGGAGG7529 AspThrThrLysValTyrValThrAsnProAspAsnValGlyArgArg 234523502355 GTGGACAAGGTGACCTTCTGGCGTGCTCCTAGGGTTCATGATAAGTAC7577 ValAspLysValThrPheTrpArgAlaProArgValHisAspLysTyr 236023652370 CTCGTGGACTCTATTGAGCGCGCTAAGAGGGCCGCTCAAGCCTGCCTA7625 LeuValAspSerIleGluArgAlaLysArgAlaAlaGlnAlaCysLeu 237523802385 AGCATGGGTTACACTTATGAGGAAGCAATAAGGACTGTAAGGCCACAT7673 SerMetGlyTyrThrTyrGluGluAlaIleArgThrValArgProHis 2390239524002405 GCTGCCATGGGCTGGGGATCTAAGGTGTCGGTTAAGGACTTAGCCACC7721 AlaAlaMetGlyTrpGlySerLysValSerValLysAspLeuAlaThr 241024152420 CCCGCGGGGAAGATGGCCGTCCATGACCGGCTTCAGGAGATACTTGAA7769 ProAlaGlyLysMetAlaValHisAspArgLeuGlnGluIleLeuGlu 242524302435 GGGACTCCGGTCCCCTTTACTCTTACTGTGAAAAAGGAGGTGTTCTTC7817 GlyThrProValProPheThrLeuThrValLysLysGluValPhePhe 244024452450 AAAGACCGGAAGGAGGAGAAGGCCCCCCGCCTCATTGTGTTCCCCCCC7865 LysAspArgLysGluGluLysAlaProArgLeuIleValPheProPro 245524602465 CTGGACTTCCGGATAGCTGAAAAGCTCATCTTGGGAGACCCAGGCCGG7913 LeuAspPheArgIleAlaGluLysLeuIleLeuGlyAspProGlyArg 2470247524802485 GTAGCCAAGGCGGTGTTGGGGGGGGCCTACGCCTTCCAGTACACCCCA7961 ValAlaLysAlaValLeuGlyGlyAlaTyrAlaPheGlnTyrThrPro 249024952500 AATCAGCGAGTTAAGGAGATGCTCAAGCTATGGGAGTCTAAGAAGACC8009 AsnGlnArgValLysGluMetLeuLysLeuTrpGluSerLysLysThr 250525102515 CCTTGCGCCATCTGTGTGGACGCCACCTGCTTCGACAGTAGCATAACT8057 ProCysAlaIleCysValAspAlaThrCysPheAspSerSerIleThr 252025252530 GAAGAGGACGTGGCTTTGGAGACAGAGCTATACGCTCTGGCCTCTGAC8105 GluGluAspValAlaLeuGluThrGluLeuTyrAlaLeuAlaSerAsp 253525402545 CATCCAGAATGGGTGCGGGCACTTGGGAAATACTATGCCTCAGGCACC8153 HisProGluTrpValArgAlaLeuGlyLysTyrTyrAlaSerGlyThr 2550255525602565 ATGGTCACCCCGGAAGGGGTGCCCGTCGGTGAGAGGTATTGCAGATCC8201 MetValThrProGluGlyValProValGlyGluArgTyrCysArgSer 257025752580 TCGGGTGTCCTAACAACTAGCGCGAGCAACTGCTTGACCTGCTACATC8249 SerGlyValLeuThrThrSerAlaSerAsnCysLeuThrCysTyrIle 258525902595 AAGGTGAAAGCTGCCTGTGAGAGAGTGGGGCTGAAAAATGTCTCTCTT8297 LysValLysAlaAlaCysGluArgValGlyLeuLysAsnValSerLeu 260026052610 CTCATAGCCGGCGATGACTGCTTGATCATATGTGAGCGGCCAGTGTGC8345 LeuIleAlaGlyAspAspCysLeuIleIleCysGluArgProValCys 261526202625 GACCCAAGCGACGCTTTGGGCAGAGCCCTAGCGAGCTATGGGTACGCG8393 AspProSerAspAlaLeuGlyArgAlaLeuAlaSerTyrGlyTyrAla 2630263526402645 TGCGAGCCCTCATATCATGCATCATTGGACACGGCCCCCTTCTGCTCC8441 CysGluProSerTyrHisAlaSerLeuAspThrAlaProPheCysSer 265026552660 ACTTGGCTTGCTGAGTGCAATGCAGATGGGAAGCGCCATTTCTTCCTG8489 ThrTrpLeuAlaGluCysAsnAlaAspGlyLysArgHisPhePheLeu 266526702675 ACCACGGACTTCCGGAGGCCGCTCGCTCGCATGTCGAGTGAGTATAGT8537 ThrThrAspPheArgArgProLeuAlaArgMetSerSerGluTyrSer 268026852690 GACCCGATGGCTTCGGCGATCGGTTACATCCTCCTTTATCCTTGGCAC8585 AspProMetAlaSerAlaIleGlyTyrIleLeuLeuTyrProTrpHis 269527002705 CCCATCACACGGTGGGTCATCATCCCTCATGTGCTAACGTGCGCATTC8633 ProIleThrArgTrpValIleIleProHisValLeuThrCysAlaPhe 2710271527202725 AGGGGTGGAGGCACACCGTCTGATCCGGTTTGGTGCCAGGTGCATGGT8681 ArgGlyGlyGlyThrProSerAspProValTrpCysGlnValHisGly 273027352740 AACTACTACAAGTTTCCACTGGACAAACTGCCTAACATCATCGTGGCC8729 AsnTyrTyrLysPheProLeuAspLysLeuProAsnIleIleValAla 274527502755 CTCCACGGACCAGCAGCGTTGAGGGTTACCGCAGACACAACTAAAACA8777 LeuHisGlyProAlaAlaLeuArgValThrAlaAspThrThrLysThr 276027652770 AAGATGGAGGCTGGTAAGGTTCTGAGCGACCTCAAGCTCCCTGGCTTA8825 LysMetGluAlaGlyLysValLeuSerAspLeuLysLeuProGlyLeu 277527802785 GCAGTCCACCGAAAGAAGGCCGGGGCGTTGCGAACACGCATGCTCCGC8873 AlaValHisArgLysLysAlaGlyAlaLeuArgThrArgMetLeuArg 2790279528002805 TCGCGCGGTTGGGCTGAGTTGGCTAGGGGCTTGTTGTGGCATCCAGGC8921 SerArgGlyTrpAlaGluLeuAlaArgGlyLeuLeuTrpHisProGly 281028152820 CTACGGCTTCCTCCCCCTGAGATTGCTGGTATCCCGGGGGGTTTCCCT8969 LeuArgLeuProProProGluIleAlaGlyIleProGlyGlyPhePro 282528302835 CTCTCCCCCCCCTATATGGGGGTGGTACATCAATTGGATTTCACAAGC9017 LeuSerProProTyrMetGlyValValHisGlnLeuAspPheThrSer 284028452850 CAGAGGAGTCGCTGGCGGTGGTTGGGGTTCTTAGCCCTGCTCATCGTA9065 GlnArgSerArgTrpArgTrpLeuGlyPheLeuAlaLeuLeuIleVal 285528602865 GCCCTCTTCGGGTGAACTAAATTCATCTGTTGCGGCAAGGTCTGGTGACTGA9117 AlaLeuPheGly 2870 TCATCACCGGAGGAGGTTCCCGCCCTCCCCGCCCCAGGGGTCTCCCCGCTGGGTAAAAAG9177 GGCCCGGCCTTGGGAGGCATGGTGGTTACTAACCCCCTGGCAGGGTCAAAGCCTGATGGT9237 GCTAATGCACTGCCACTTCGGTGGCGGGTCGCTACCTTATAGCGTAATCCGTGACTACGG9297 GCTGCTCGCAGAGCCCTCCCCGGATGGGGCACAGTGCACTGTGATCTGAAGGGGTGCACC9357 CCGGGAAGAGCTCGGCCCGAAGGCCGGTTCTACT9391 (2) INFORMATION FOR SEQ ID NO:2: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 2873 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULE TYPE: protein (xi) SEQUENCE DESCRIPTION: SEQ ID NO:2: MetGlyProProSerSerAlaAlaAlaCysSerArgGlySerProArg 151015 IleLeuArgValArgAlaGlyGlyIleSerPhePheTyrThrIleMet 202530 AlaValLeuLeuLeuLeuLeuValValGluAlaGlyAlaIleLeuAla 354045 ProAlaThrHisAlaCysArgAlaAsnGlyGlnTyrPheLeuThrAsn 505560 CysCysAlaProGluAspIleGlyPheCysLeuGluGlyGlyCysLeu 65707580 ValAlaLeuGlyCysThrIleCysThrAspGlnCysTrpProLeuTyr 859095 GlnAlaGlyLeuAlaValArgProGlyLysSerAlaAlaGlnLeuVal 100105110 GlyGluLeuGlySerLeuTyrGlyProLeuSerValSerAlaTyrVal 115120125 AlaGlyIleLeuGlyLeuGlyGluValTyrSerGlyValLeuThrVal 130135140 GlyValAlaLeuThrArgArgValTyrProValProAsnLeuThrCys 145150155160 AlaValAlaCysGluLeuLysTrpGluSerGluPheTrpArgTrpThr 165170175 GluGlnLeuAlaSerAsnTyrTrpIleLeuGluTyrLeuTrpLysVal 180185190 ProPheAspPheTrpArgGlyValIleSerLeuThrProLeuLeuVal 195200205 CysValAlaAlaLeuLeuLeuLeuGluGlnArgIleValMetValPhe 210215220 LeuLeuValThrMetAlaGlyMetSerGlnGlyAlaProAlaSerVal 225230235240 LeuGlySerArgProPheAspTyrGlyLeuThrTrpGlnThrCysSer 245250255 CysArgAlaAsnGlySerArgPheSerThrGlyGluLysValTrpAsp 260265270 ArgGlyAsnValThrLeuGlnCysAspCysProAsnGlyProTrpVal 275280285 TrpLeuProAlaPheCysGlnAlaIleGlyTrpGlyAspProIleThr 290295300 TyrTrpSerHisGlyGlnAsnGlnTrpProLeuSerCysProGlnTyr 305310315320 ValTyrGlySerAlaThrValThrCysValTrpGlySerAlaSerTrp 325330335 PheAlaSerThrSerGlyArgAspSerLysIleAspValTrpSerLeu 340345350 ValProValGlySerAlaThrCysThrIleAlaAlaLeuGlySerSer 355360365 AspArgAspThrValProGlyLeuSerGluTrpGlyIleProCysVal 370375380 ThrCysValLeuAspArgArgProAlaSerCysGlyThrCysValArg 385390395400 AspCysTrpProGluThrGlySerValArgPheProPheHisArgCys 405410415 GlyValGlyProArgLeuThrLysAspLeuGluAlaValProPheVal 420425430 AsnArgThrThrProPheThrIleArgGlyProLeuGlyAsnGlnGly 435440445 ArgGlyAsnProValArgSerProLeuGlyPheGlySerTyrAlaMet 450455460 ThrArgIleArgAspThrLeuHisLeuValGluCysProThrProAla 465470475480 IleGluProProThrGlyThrPheGlyPhePheProGlyThrProPro 485490495 LeuAsnAsnCysMetLeuLeuGlyThrGluValSerGluAlaLeuGly 500505510 GlyAlaGlyLeuThrGlyGlyPheTyrGluProLeuValArgArgCys 515520525 SerLysLeuMetGlySerArgAsnProValCysProGlyPheAlaTrp 530535540 LeuSerSerGlyArgProAspGlyPheIleHisValGlnGlyHisLeu 545550555560 GlnGluValAspAlaGlyAsnPheIleProProProArgTrpLeuLeu 565570575 LeuAspPheValPheValLeuLeuTyrLeuMetLysLeuAlaGluAla 580585590 ArgLeuValProLeuIleLeuLeuLeuLeuTrpTrpTrpValAsnGln 595600605 LeuAlaValLeuGlyLeuProAlaValGluAlaAlaValAlaGlyGlu 610615620 ValPheAlaGlyProAlaLeuSerTrpCysLeuGlyLeuProValVal 625630635640 SerMetIleLeuGlyLeuAlaAsnLeuValLeuTyrPheArgTrpLeu 645650655 GlyProGlnArgLeuMetPheLeuValLeuTrpLysLeuAlaArgGly 660665670 AlaPheProLeuAlaLeuLeuMetGlyIleSerAlaThrArgGlyArg 675680685 ThrSerValLeuGlyAlaGluPheCysPheAspAlaThrPheGluVal 690695700 AspThrSerValLeuGlyTrpValValAlaSerValValAlaTrpAla 705710715720 IleAlaLeuLeuSerSerMetSerAlaGlyGlyTrpArgHisLysAla 725730735 ValIleTyrArgThrTrpCysLysGlyTyrGlnAlaIleArgGlnArg 740745750 ValValArgSerProLeuGlyGluGlyArgProAlaLysProLeuThr 755760765 PheAlaTrpCysLeuAlaSerTyrIleTrpProAspAlaValMetMet 770775780 ValValValAlaLeuValLeuLeuPheGlyLeuPheAspAlaLeuAsp 785790795800 TrpAlaLeuGluGluIleLeuValSerArgProSerLeuArgArgLeu 805810815 AlaArgValValGluCysCysValMetAlaGlyGluLysAlaThrThr 820825830 ValArgLeuValSerLysMetCysAlaArgGlyAlaTyrLeuPheAsp 835840845 HisMetGlySerPheSerArgAlaValLysGluArgLeuLeuGluTrp 850855860 AspAlaAlaLeuGluProLeuSerPheThrArgThrAspCysArgIle 865870875880 IleArgAspAlaAlaArgThrLeuSerCysGlyGlnCysValMetGly 885890895 LeuProValValAlaArgArgGlyAspGluValLeuIleGlyValPhe 900905910 GlnAspValAsnHisLeuProProGlyPheValProThrAlaProVal 915920925 ValIleArgArgCysGlyLysGlyPheLeuGlyValThrLysAlaAla 930935940 LeuThrGlyArgAspProAspLeuHisProGlyAsnValMetValLeu 945950955960 GlyThrAlaThrSerArgSerMetGlyThrCysLeuAsnGlyLeuLeu 965970975 PheThrThrPheHisGlyAlaSerSerArgThrIleAlaThrProVal 980985990 GlyAlaLeuAsnProArgTrpTrpSerAlaSerAspAspValThrVal 99510001005 TyrProLeuProAspGlyAlaThrSerLeuThrProCysThrCysGln 101010151020 AlaGluSerCysTrpValIleArgSerAspGlyAlaLeuCysHisGly 1025103010351040 LeuSerLysGlyAspLysValGluLeuAspValAlaMetGluValSer 104510501055 AspPheArgGlySerSerGlySerProValLeuCysAspGluGlyHis 106010651070 AlaValGlyMetLeuValSerValLeuHisSerGlyGlyArgValThr 107510801085 AlaAlaArgPheThrArgProTrpThrGlnValProThrAspAlaLys 109010951100 ThrThrThrGluProProProValProAlaLysGlyValPheLysGlu 1105111011151120 AlaProLeuPheMetProThrGlyAlaGlyLysSerThrArgValPro 112511301135 LeuGluTyrAspAsnMetGlyHisLysValLeuIleLeuAsnProSer 114011451150 ValAlaThrValArgAlaMetGlyProTyrMetGluArgLeuAlaGly 115511601165 LysHisProSerIleTyrCysGlyHisAspThrThrAlaPheThrArg 117011751180 IleThrAspSerProLeuThrTyrSerThrTyrGlyArgPheLeuAla 1185119011951200 AsnProArgGlnMetLeuArgGlyValSerValValIleCysAspGlu 120512101215 CysHisSerHisAspSerThrValLeuLeuGlyIleGlyArgValArg 122012251230 GluLeuAlaArgGlyCysGlyValGlnLeuValLeuTyrAlaThrAla 123512401245 ThrProProGlySerProMetThrGlnHisProSerIleIleGluThr 125012551260 LysLeuAspValGlyGluIleProPheTyrGlyHisGlyIleProLeu 1265127012751280 GluArgMetArgThrGlyArgHisLeuValPheCysHisSerLysAla 128512901295 GluCysGluArgLeuAlaGlyGlnPheSerAlaArgGlyValAsnAla 130013051310 IleAlaTyrTyrArgGlyLysAspSerSerIleIleLysAspGlyAsp 131513201325 LeuValValCysAlaThrAspAlaLeuSerThrGlyTyrThrGlyAsn 133013351340 PheAspSerValThrAspCysGlyLeuValValGluGluValValGlu 1345135013551360 ValThrLeuAspProThrIleThrIleSerLeuArgThrValProAla 136513701375 SerAlaGluLeuSerMetGlnArgArgGlyArgThrGlyArgGlyArg 138013851390 SerGlyArgTyrTyrTyrAlaGlyValGlyLysAlaProAlaGlyVal 139514001405 ValArgSerGlyProValTrpSerAlaValGluAlaGlyValThrTrp 141014151420 TyrGlyMetGluProAspLeuThrAlaAsnLeuLeuArgLeuTyrAsp 1425143014351440 AspCysProTyrThrAlaAlaValAlaAlaAspIleGlyGluAlaAla 144514501455 ValPhePheSerGlyLeuAlaProLeuArgMetHisProAspValSer 146014651470 TrpAlaLysValArgGlyValAsnTrpProLeuLeuValGlyValGln 147514801485 ArgThrMetCysArgGluThrLeuSerProGlyProSerAspAspPro 149014951500 GlnTrpAlaGlyLeuLysGlyProAsnProValProLeuLeuLeuArg 1505151015151520 TrpGlyAsnAspLeuProSerLysValAlaGlyHisHisIleValAsp 152515301535 AspLeuValArgArgLeuGlyValAlaGluGlyTyrValArgCysAsp 154015451550 AlaGlyProIleLeuMetIleGlyLeuAlaIleAlaGlyGlyMetIle 155515601565 TyrAlaSerTyrThrGlySerLeuValValValThrAspTrpAspVal 157015751580 LysGlyGlyGlyAlaProLeuTyrArgHisGlyAspGlnAlaThrPro 1585159015951600 GlnProValValGlnValProProValAspHisArgProGlyGlyGlu 160516101615 SerAlaProSerAspAlaLysThrValThrAspAlaValAlaAlaIle 162016251630 GlnValAspCysAspTrpThrIleMetThrLeuSerIleGlyGluVal 163516401645 LeuSerLeuAlaGlnAlaLysThrAlaGluAlaTyrThrAlaThrAla 165016551660 LysTrpLeuAlaGlyCysTyrThrGlyThrArgAlaValProThrVal 1665167016751680 SerIleValAspLysLeuPheAlaGlyGlyTrpAlaAlaValValGly 168516901695 HisCysHisSerValIleAlaAlaAlaValAlaAlaTyrGlyAlaSer 170017051710 ArgSerProProLeuAlaAlaAlaAlaSerTyrLeuMetGlyLeuGly 171517201725 ValGlyGlyAsnAlaGlnThrArgLeuAlaSerAlaLeuLeuLeuGly 173017351740 AlaAlaGlyThrAlaLeuGlyThrProValValGlyLeuThrMetAla 1745175017551760 GlyAlaPheMetGlyGlyAlaSerValSerProSerLeuValThrIle 176517701775 LeuLeuGlyAlaValGlyGlyTrpGluGlyValValAsnAlaAlaSer 178017851790 LeuValPheAspPheMetAlaGlyLysLeuSerSerGluAspLeuTrp 179518001805 TyrAlaIleProValLeuThrSerProGlyAlaGlyLeuAlaGlyIle 181018151820 AlaLeuGlyLeuValLeuTyrSerAlaAsnAsnSerGlyThrThrThr 1825183018351840 TrpLeuAsnArgLeuLeuThrThrLeuProArgSerSerCysIlePro 184518501855 AspSerTyrPheGlnGlnValAspTyrCysAspLysValSerAlaVal 186018651870 LeuArgArgLeuSerLeuThrArgThrValValAlaLeuValAsnArg 187518801885 GluProLysValAspGluValGlnValGlyTyrValTrpAspLeuTrp 189018951900 GluTrpIleMetArgGlnValArgValValMetAlaArgLeuArgAla 1905191019151920 LeuCysProValValSerLeuProLeuTrpHisCysGlyGluGlyTrp 192519301935 SerGlyGluTrpLeuLeuAspGlyHisValGluSerArgCysLeuCys 194019451950 GlyCysValIleThrGlyAspValLeuAsnGlyGlnLeuLysGluPro 195519601965 ValTyrSerThrLysLeuCysArgHisTyrTrpMetGlyThrValPro 197019751980 ValAsnMetLeuGlyTyrGlyGluThrSerProLeuLeuAlaSerAsp 1985199019952000 ThrProLysValValProPheGlyThrSerGlyTrpAlaGluValVal 200520102015 ValThrThrThrHisValValIleArgArgThrSerAlaTyrLysLeu 202020252030 LeuArgGlnGlnIleLeuSerAlaAlaValAlaGluProTyrTyrVal 203520402045 AspGlyIleProValSerTrpAspAlaAspAlaArgAlaProAlaMet 205020552060 ValTyrGlyProGlyGlnSerValThrIleAspGlyGluArgTyrThr 2065207020752080 LeuProHisGlnLeuArgLeuArgAsnValAlaProSerGluValSer 208520902095 SerGluValSerIleAspIleGlyThrGluThrGluAspSerGluLeu 210021052110 ThrGluAlaAspLeuProProAlaAlaAlaAlaLeuGlnAlaIleGlu 211521202125 AsnAlaAlaArgIleLeuGluProHisIleAspValIleMetGluAsp 213021352140 CysSerThrProSerLeuCysGlySerSerArgGluMetProValTrp 2145215021552160 GlyGluAspIleProArgThrProSerProAlaLeuIleSerValThr 216521702175 GluSerSerSerAspGluLysThrProSerValSerSerSerGlnGlu 218021852190 AspThrProSerSerAspSerPheGluValIleGlnGluSerGluThr 219522002205 AlaGluGlyGluGluSerValPheAsnValAlaLeuSerValLeuLys 221022152220 AlaLeuPheProGlnSerAspAlaThrArgLysLeuThrValLysMet 2225223022352240 SerCysCysValGluLysSerValThrArgPhePheSerLeuGlyLeu 224522502255 ThrValAlaAspValAlaSerLeuCysGluMetGluIleGlnAsnHis 226022652270 ThrAlaTyrCysAspGlnValArgThrProLeuGluLeuGlnValGly 227522802285 CysLeuValGlyAsnGluLeuThrPheGluCysAspLysCysGluAla 229022952300 ArgGlnGluThrLeuAlaSerPheSerTyrIleTrpSerGlyValPro 2305231023152320 LeuThrArgAlaThrProAlaLysProProValValArgProValGly 232523302335 SerLeuLeuValAlaAspThrThrLysValTyrValThrAsnProAsp 234023452350 AsnValGlyArgArgValAspLysValThrPheTrpArgAlaProArg 235523602365 ValHisAspLysTyrLeuValAspSerIleGluArgAlaLysArgAla 237023752380 AlaGlnAlaCysLeuSerMetGlyTyrThrTyrGluGluAlaIleArg 2385239023952400 ThrValArgProHisAlaAlaMetGlyTrpGlySerLysValSerVal 240524102415 LysAspLeuAlaThrProAlaGlyLysMetAlaValHisAspArgLeu 242024252430 GlnGluIleLeuGluGlyThrProValProPheThrLeuThrValLys 243524402445 LysGluValPhePheLysAspArgLysGluGluLysAlaProArgLeu 245024552460 IleValPheProProLeuAspPheArgIleAlaGluLysLeuIleLeu 2465247024752480 GlyAspProGlyArgValAlaLysAlaValLeuGlyGlyAlaTyrAla 248524902495 PheGlnTyrThrProAsnGlnArgValLysGluMetLeuLysLeuTrp 250025052510 GluSerLysLysThrProCysAlaIleCysValAspAlaThrCysPhe 251525202525 AspSerSerIleThrGluGluAspValAlaLeuGluThrGluLeuTyr 253025352540 AlaLeuAlaSerAspHisProGluTrpValArgAlaLeuGlyLysTyr 2545255025552560 TyrAlaSerGlyThrMetValThrProGluGlyValProValGlyGlu 256525702575 ArgTyrCysArgSerSerGlyValLeuThrThrSerAlaSerAsnCys 258025852590 LeuThrCysTyrIleLysValLysAlaAlaCysGluArgValGlyLeu 259526002605 LysAsnValSerLeuLeuIleAlaGlyAspAspCysLeuIleIleCys 261026152620 GluArgProValCysAspProSerAspAlaLeuGlyArgAlaLeuAla 2625263026352640 SerTyrGlyTyrAlaCysGluProSerTyrHisAlaSerLeuAspThr 264526502655 AlaProPheCysSerThrTrpLeuAlaGluCysAsnAlaAspGlyLys 266026652670 ArgHisPhePheLeuThrThrAspPheArgArgProLeuAlaArgMet 267526802685 SerSerGluTyrSerAspProMetAlaSerAlaIleGlyTyrIleLeu 269026952700 LeuTyrProTrpHisProIleThrArgTrpValIleIleProHisVal 2705271027152720 LeuThrCysAlaPheArgGlyGlyGlyThrProSerAspProValTrp 272527302735 CysGlnValHisGlyAsnTyrTyrLysPheProLeuAspLysLeuPro 274027452750 AsnIleIleValAlaLeuHisGlyProAlaAlaLeuArgValThrAla 275527602765 AspThrThrLysThrLysMetGluAlaGlyLysValLeuSerAspLeu 277027752780 LysLeuProGlyLeuAlaValHisArgLysLysAlaGlyAlaLeuArg 2785279027952800 ThrArgMetLeuArgSerArgGlyTrpAlaGluLeuAlaArgGlyLeu 280528102815 LeuTrpHisProGlyLeuArgLeuProProProGluIleAlaGlyIle 282028252830 ProGlyGlyPheProLeuSerProProTyrMetGlyValValHisGln 283528402845 LeuAspPheThrSerGlnArgSerArgTrpArgTrpLeuGlyPheLeu 285028552860 AlaLeuLeuIleValAlaLeuPheGly 28652870 (2) INFORMATION FOR SEQ ID NO:3: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 360 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: double (D) TOPOLOGY: linear (ii) MOLECULE TYPE: cDNA (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: (C) INDIVIDUAL ISOLATE: NS2B Protease Region (xi) SEQUENCE DESCRIPTION: SEQ ID NO:3: ATCTTGGTGTCCCGGCCCTCGTTGCGGCGTTTGGCTCGGGTGGTTGAGTGCTGTGTGATG60 GCGGGTGAGAAGGCCACAACCGTCCGGCTGGTCTCCAAGATGTGTGCGAGAGGAGCTTAT120 TTGTTCGATCATATGGGCTCTTTTTCGCGTGCTGTCAAGGAGCGCCTGTTGGAATGGGAC180 GCAGCTCTTGAACCTCTGTCATTCACTAGGACGGACTGTCGCATCATACGGGATGCCGCG240 AGGACTTTGTCCTGCGGGCAGTGCGTCATGGGTTTACCCGTGGTTGCGCGCCGTGGTGAT300 GAGGTTCTCATCGGCGTCTTCCAGGATGTGAATCATTTGCCTCCCGGGTTTGTTCCGACC360 (2) INFORMATION FOR SEQ ID NO:4: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 573 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: double (D) TOPOLOGY: linear (ii) MOLECULE TYPE: cDNA (vi) ORIGINAL SOURCE: (C) INDIVIDUAL ISOLATE: NS3 protease region (xi) SEQUENCE DESCRIPTION: SEQ ID NO:4: GCGCCTGTTGTCATCCGACGGTGCGGAAAGGGCTTCTTGGGGGTCACAAAGGCTGCCTTG60 ACAGGTCGGGATCCTGACTTACATCCAGGGAACGTCATGGTGTTGGGGACGGCTACGTCG120 CGAAGCATGGGAACATGCTTGAACGGCCTGCTGTTCACGACCTTCCATGGGGCTTCATCC180 CGAACCATCGCCACACCCGTGGGGGCCCTTAATCCCAGATGGTGGTCAGCCAGTGATGAT240 GTCACGGTGTATCCACTCCCGGATGGGGCTACTTCGTTAACACCTTGTACTTGCCAGGCT300 GAGTCCTGTTGGGTCATCAGATCCGACGGGGCCCTATGCCATGGCTTGAGCAAGGGGGAC360 AAGGTGGAGCTGGATGTGGCCATGGAGGTCTCTGACTTCCGTGGCTCGTCTGGCTCACCG420 GTCCTATGTGACGAAGGGCACGCAGTAGGAATGCTCGTGTCTGTGCTTCACTCCGGTGGT480 AGGGTCACCGCGGCACGGTTCACTAGGCCGTGGACCCAAGTGCCAACAGATGCCAAAACC540 ACTACTGAACCCCCTCCGGTGCCGGCCAAAGGA573 (2) INFORMATION FOR SEQ ID NO:5: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 147 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: double (D) TOPOLOGY: linear (ii) MOLECULE TYPE: cDNA (vi) ORIGINAL SOURCE: (C) INDIVIDUAL ISOLATE: NS4A-B protease region (xi) SEQUENCE DESCRIPTION: SEQ ID NO:5: CGCTGCGACGCTGGGCCGATCTTGATGATCGGTCTAGCTATCGCGGGGGGAATGATCTAC60 GCGTCATACACCGGGTCGCTAGTGGTGGTGACAGACTGGGATGTGAAGGGGGGTGGCGCC120 CCCCTTTATCGGCATGGAGACCAGGCC147 (2) INFORMATION FOR SEQ ID NO:6: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 9 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (vi) ORIGINAL SOURCE: (C) INDIVIDUAL ISOLATE: Catalytic His region of HGV NS3 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:6: LeuPheThrThrPheHisGlyAlaSer 15 (2) INFORMATION FOR SEQ ID NO:7: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 9 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (vi) ORIGINAL SOURCE: (C) INDIVIDUAL ISOLATE: Catalytic Asp region of HGV NS3 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:7: AlaSerAspAspValThrValTyrPro 15 (2) INFORMATION FOR SEQ ID NO:8: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 9 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (vi) ORIGINAL SOURCE: (C) INDIVIDUAL ISOLATE: Catalytic Ser region of HGV NS3 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:8: PheArgGlySerSerGlySerProVal 15 (2) INFORMATION FOR SEQ ID NO:9: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 9 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (vi) ORIGINAL SOURCE: (C) INDIVIDUAL ISOLATE: catalytic His region of HCV NS3 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:9: CysTrpThrValTyrHisGlyAlaGly 15 (2) INFORMATION FOR SEQ ID NO:10: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 8 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (vi) ORIGINAL SOURCE: (C) INDIVIDUAL ISOLATE: Catalytic Asp region of HCV NS3 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:10: AspAspLeuGlyTrpProAlaPro 15 (2) INFORMATION FOR SEQ ID NO:11: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 9 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (vi) ORIGINAL SOURCE: (C) INDIVIDUAL ISOLATE: Catalytic Ser region of HCV NS3 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:11: LeuLysGlySerSerGlyGlyProLeu 15 (2) INFORMATION FOR SEQ ID NO:12: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 9 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (vi) ORIGINAL SOURCE: (C) INDIVIDUAL ISOLATE: Catalytic His region of Yellow Fever Virus NS3 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:12: PheHisThrMetTrpHisValThrArg 15 (2) INFORMATION FOR SEQ ID NO:13: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 9 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (vi) ORIGINAL SOURCE: (C) INDIVIDUAL ISOLATE: catalytic Asp region of Yellow Fever Virus NS3 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:13: LysGluAspLeuValAlaThrGlyGly 15 (2) INFORMATION FOR SEQ ID NO:14: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 9 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (vi) ORIGINAL SOURCE: (C) INDIVIDUAL ISOLATE: catalytic Ser region of Yellow Fever Virus NS3 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:14: ProSerGlyThrSerGlySerProIle 15 (2) INFORMATION FOR SEQ ID NO:15: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 9 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (vi) ORIGINAL SOURCE: (C) INDIVIDUAL ISOLATE: catalytic His region of West Nile Fever Virus NS3 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:15: PheHisThrLeuTrpHisThrThrLys 15 (2) INFORMATION FOR SEQ ID NO:16: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 9 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (vi) ORIGINAL SOURCE: (C) INDIVIDUAL ISOLATE: catalytic Asp region of West Nile Fever Virus NS3 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:16: LysGluAspArgLeuCysTyrGlyGly 15 (2) INFORMATION FOR SEQ ID NO:17: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 9 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (vi) ORIGINAL SOURCE: (C) INDIVIDUAL ISOLATE: catalytic Ser region of West Nile Fever Virus NS2B (xi) SEQUENCE DESCRIPTION: SEQ ID NO:17: ProThrGlyThrSerGlySerProIle 15 (2) INFORMATION FOR SEQ ID NO:18: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 9 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (vi) ORIGINAL SOURCE: (C) INDIVIDUAL ISOLATE: catalytic His region of Murray Valley Virus NS3 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:18: PheHisThrLeuTrpHisThrThrArg 15 (2) INFORMATION FOR SEQ ID NO:19: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 9 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (vi) ORIGINAL SOURCE: (C) INDIVIDUAL ISOLATE: catalytic Asp region of Murray Valley Virus NS3 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:19: LysGluAspArgValThrTyrGlyGly 15 (2) INFORMATION FOR SEQ ID NO:20: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 9 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (vi) ORIGINAL SOURCE: (C) INDIVIDUAL ISOLATE: catalytic Ser region of Murray Valley Virus NS3 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:20: ProThrGlyThrSerGlySerProIle 15 (2) INFORMATION FOR SEQ ID NO:21: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 9 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (vi) ORIGINAL SOURCE: (C) INDIVIDUAL ISOLATE: catalytic His region of Kunjin Virus NS# (xi) SEQUENCE DESCRIPTION: SEQ ID NO:21: PheHisThrLeuTrpHisThrThrLys 15 (2) INFORMATION FOR SEQ ID NO:22: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 9 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (vi) ORIGINAL SOURCE: (C) INDIVIDUAL ISOLATE: catalytic Asp region of Kunjin Virus NS3 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:22: LysGluAspArgLeuCysTyrGlyGly 15 (2) INFORMATION FOR SEQ ID NO:23: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 9 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (vi) ORIGINAL SOURCE: (C) INDIVIDUAL ISOLATE: catalytic Ser region of Kunjin Virus NS3 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:23: ProThrGlyThrSerGlySerProIle 15 (2) INFORMATION FOR SEQ ID NO:24: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 2561 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: DNA (genomic) (vi) ORIGINAL SOURCE: (C) INDIVIDUAL ISOLATE: HGV DNA contained in vector "L" (ix) FEATURE: (A) NAME/KEY: CDS (B) LOCATION: 2..2560 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:24: GATCTTGGTGTCCCGGCCCTCGCTGCGGCGTTTGGCTCGGGTGGTT46 IleLeuValSerArgProSerLeuArgArgLeuAlaArgValVal 151015 GAGTGCTGTGTGATGGCGGGTGAGAAGGCCACAACCGTCCGGCTGGTC94 GluCysCysValMetAlaGlyGluLysAlaThrThrValArgLeuVal 202530 TCCAAGATGTGTGCGAGAGGAGCTTATTTGTTCGATCATATGGGCTCA142 SerLysMetCysAlaArgGlyAlaTyrLeuPheAspHisMetGlySer 354045 TTTTCGCGTGCTGTCAAGGAGCGCCTGTTGGAATGGGACGCGGCTCTT190 PheSerArgAlaValLysGluArgLeuLeuGluTrpAspAlaAlaLeu 505560 GAACCTCTGTCATTCACTAGGACGGACTGTCGCATCATACGGGATGCC238 GluProLeuSerPheThrArgThrAspCysArgIleIleArgAspAla 657075 GCGAGGACTTTGTCCTGCGGGCAATGCGTCATGGGTTTACCCGTGGTT286 AlaArgThrLeuSerCysGlyGlnCysValMetGlyLeuProValVal 80859095 GCGCGCCGTGGTGATGAGGTTCTCATCGGCGTCTTCCAGGATGTGAAT334 AlaArgArgGlyAspGluValLeuIleGlyValPheGlnAspValAsn 100105110 CATTTGCCTCCCGGGTTTGTTCCGACCGCGCCTGTTGTCATCCGACGG382 HisLeuProProGlyPheValProThrAlaProValValIleArgArg 115120125 TGCGGAAAGGGCTTCTTGGGGGTCACAAAGGCTGCCTTGACAGGTCGG430 CysGlyLysGlyPheLeuGlyValThrLysAlaAlaLeuThrGlyArg 130135140 GATCCTGACTTACATCCAGGGAACGTCATGGTGTTGGGGACGGCTACG478 AspProAspLeuHisProGlyAsnValMetValLeuGlyThrAlaThr 145150155 TCGCGAAGCATGGGAACATGCTTGAACGGCCTGCTGTTCACGACCTTC526 SerArgSerMetGlyThrCysLeuAsnGlyLeuLeuPheThrThrPhe 160165170175 CATGGGGCTTCATCCCGAACCATCGCCACACCCGTGGGGGCCCTTAAT574 HisGlyAlaSerSerArgThrIleAlaThrProValGlyAlaLeuAsn 180185190 CCCAGATGGTGGTCAGCCAGTGATGATGTCACGGTGTATCCACTCCCG622 ProArgTrpTrpSerAlaSerAspAspValThrValTyrProLeuPro 195200205 GATGGGGCTACTTCGTTAACGCCTTGTACTTGCCAGGCTGAGTCCTGT670 AspGlyAlaThrSerLeuThrProCysThrCysGlnAlaGluSerCys 210215220 TGGGTCATCAGATCCGACGGGGCCCTATGCCATGGCTTGAGCAAGGGG718 TrpValIleArgSerAspGlyAlaLeuCysHisGlyLeuSerLysGly 225230235 GACAAGGTGGAGCTGGATGTGGCCATGGAGGTCCCTGATTTCCGTGGC766 AspLysValGluLeuAspValAlaMetGluValProAspPheArgGly 240245250255 TCGTCTGGCTCACCGGTCCTATGTGACGAGGGGCACGCAGTAGGAATG814 SerSerGlySerProValLeuCysAspGluGlyHisAlaValGlyMet 260265270 CTCGTGTCTGTGCTTCACTCCGGTGGTAGGGTCACCGCGGCACGGTTC862 LeuValSerValLeuHisSerGlyGlyArgValThrAlaAlaArgPhe 275280285 ACTAGGCCGTGGACCCAAGTGCCAACAGATGCCAAAACCACCACTGAA910 ThrArgProTrpThrGlnValProThrAspAlaLysThrThrThrGlu 290295300 CCCCCTCCGGTGCCGGCCAAAGGAGTTTTCAAAGAGGCCCCGTTGTTT958 ProProProValProAlaLysGlyValPheLysGluAlaProLeuPhe 305310315 ATGCCTACGGGAGCGGGAAAGAGCACTCGCGTCCCGTTGGAGTACGGC1006 MetProThrGlyAlaGlyLysSerThrArgValProLeuGluTyrGly 320325330335 AACATGGGGCACAAGGTCTTAGTCTTGAACCCCTCAGTGGCCACTGTG1054 AsnMetGlyHisLysValLeuValLeuAsnProSerValAlaThrVal 340345350 CGGGCCATGGGCCCGTACATGGAGCGGCTGGCGGGTAAACATCCAAGT1102 ArgAlaMetGlyProTyrMetGluArgLeuAlaGlyLysHisProSer 355360365 ATATACTGTGGGCATGATACAACTGCTTTCACAAGGATCACTGACTCC1150 IleTyrCysGlyHisAspThrThrAlaPheThrArgIleThrAspSer 370375380 CCCCTGACGTATTCAACCTATGGGAGGTTTTTGGCCAACCCTAGGCAG1198 ProLeuThrTyrSerThrTyrGlyArgPheLeuAlaAsnProArgGln 385390395 ATGCTACGGGGCGTTTCGGTGGTCATTTGTGATGAGTGCCACAGTTAT1246 MetLeuArgGlyValSerValValIleCysAspGluCysHisSerTyr 400405410415 GACTCAACCGTGCTGTTAGGCATTGGGAGGGTTCGGGAGCTGGCGCGT1294 AspSerThrValLeuLeuGlyIleGlyArgValArgGluLeuAlaArg 420425430 GGGTGCGGAGTGCAACTAGTGCTCTACGCCACCGCTACGCCTCCCGGA1342 GlyCysGlyValGlnLeuValLeuTyrAlaThrAlaThrProProGly 435440445 TCCCCTATGACGCAGCACCCTTCCATAATTGAGACAAAATTGGACGTG1390 SerProMetThrGlnHisProSerIleIleGluThrLysLeuAspVal 450455460 GGCGAGATTCCCTTTTATGGGCACGGAATACCCCTCGAGCGGATGCGA1438 GlyGluIleProPheTyrGlyHisGlyIleProLeuGluArgMetArg 465470475 ACCGGAAGGCACCTCGTGTTCTGCCATTCTAAGGCTGAGTGCGAGCGC1486 ThrGlyArgHisLeuValPheCysHisSerLysAlaGluCysGluArg 480485490495 CTTGCTGGCCAGTTCTCCGCTAGGGGGGTCAATGCCATTGCCTATTAT1534 LeuAlaGlyGlnPheSerAlaArgGlyValAsnAlaIleAlaTyrTyr 500505510 AGGGGTAAAGACAGTTCTATCATCAAGGATGGGGACCTGGTGGTCTGT1582 ArgGlyLysAspSerSerIleIleLysAspGlyAspLeuValValCys 515520525 GCCACAGACGCGCTTTCCACTGGGTACACTGGAAATTTCGACTCCGTC1630 AlaThrAspAlaLeuSerThrGlyTyrThrGlyAsnPheAspSerVal 530535540 ACCGACTGTGGATTAGTGGTGGAGGAGGTCGTTGAGGTGACCCTTGAT1678 ThrAspCysGlyLeuValValGluGluValValGluValThrLeuAsp 545550555 CCTACCATTACCATCTCCCTGCGGACAGTGCCTGCGTCGGCTGAACTG1726 ProThrIleThrIleSerLeuArgThrValProAlaSerAlaGluLeu 560565570575 TCGATGCAAAGACGAGGACGCACGGGTAGGGGCAGGTCTGGACGCTAC1774 SerMetGlnArgArgGlyArgThrGlyArgGlyArgSerGlyArgTyr 580585590 TACTACGCGGGGGTGGGCAAAGCCCCTGCGGGTGTGGTGCGCTCAGGT1822 TyrTyrAlaGlyValGlyLysAlaProAlaGlyValValArgSerGly 595600605 CCTGTCTGGTCGGCGGTGGAAGCTGGAGTGACCTGGTACGGAATGGAA1870 ProValTrpSerAlaValGluAlaGlyValThrTrpTyrGlyMetGlu 610615620 CCTGACTTGACAGCTAACCTACTGAGACTTTACGACGACTGCCCTTAC1918 ProAspLeuThrAlaAsnLeuLeuArgLeuTyrAspAspCysProTyr 625630635 ACCGCAGCCGTCGCGGCTGATATCGGAGAAGCCGCGGTGTTCTTCTCT1966 ThrAlaAlaValAlaAlaAspIleGlyGluAlaAlaValPhePheSer 640645650655 GGGCTCGCCCCATTGAGGATGCACCCTGATGTCAGCTGGGCAAAAGTT2014 GlyLeuAlaProLeuArgMetHisProAspValSerTrpAlaLysVal 660665670 CGCGGCGTCAACTGGCCCCTCTTGGTGGGTGTTCAGCGGACCATGTGT2062 ArgGlyValAsnTrpProLeuLeuValGlyValGlnArgThrMetCys 675680685 CGGGAAACACTGTCTCCCGGCCCATCGGATGACCCCCAATGGGCAGGT2110 ArgGluThrLeuSerProGlyProSerAspAspProGlnTrpAlaGly 690695700 CTGAAGGGCCCAAATCCTGTCCCACTCCTGCTGAGGTGGGGCAATGAT2158 LeuLysGlyProAsnProValProLeuLeuLeuArgTrpGlyAsnAsp 705710715 TTACCATCTAAAGTGGCCGGCCACCACATAGTGGACGACCTGGTCCGG2206 LeuProSerLysValAlaGlyHisHisIleValAspAspLeuValArg 720725730735 AGACTCGGTGTGGCGGAGGGTTACGCCCGCTGCGACGCTGGGCCGATC2254 ArgLeuGlyValAlaGluGlyTyrAlaArgCysAspAlaGlyProIle 740745750 TTGATGATCGGTCTAGCTATCGCGGGGGGAATGATCTACGCGTCGTAC2302 LeuMetIleGlyLeuAlaIleAlaGlyGlyMetIleTyrAlaSerTyr 755760765 ACCGGGTCGCTAGTGGTGGTGACAGACTGGGATGTGAAGGGGGGTGGC2350 ThrGlySerLeuValValValThrAspTrpAspValLysGlyGlyGly 770775780 GCCCCCCTTTATCGGCATGGAGACCAGGCCACGCCTCAGCCGGTGGTG2398 AlaProLeuTyrArgHisGlyAspGlnAlaThrProGlnProValVal 785790795 CAGGTTCCTCCGGTAGACCATCGGCCGGGGGGTGAATCAGCACCATCG2446 GlnValProProValAspHisArgProGlyGlyGluSerAlaProSer 800805810815 GATGCCAAGACAGTGACAGATGCGGTGGCAGCGATCCAGGTGGACTGC2494 AspAlaLysThrValThrAspAlaValAlaAlaIleGlnValAspCys 820825830 GATTGGACTATCATGACTCTGTCGATCGGAGAAGTGTTGTCCTTGGCT2542 AspTrpThrIleMetThrLeuSerIleGlyGluValLeuSerLeuAla 835840845 CAGGCTAAGACGGCCGAGG2561 GlnAlaLysThrAlaGlu 850 (2) INFORMATION FOR SEQ ID NO:25: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 853 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULE TYPE: protein (xi) SEQUENCE DESCRIPTION: SEQ ID NO:25: IleLeuValSerArgProSerLeuArgArgLeuAlaArgValValGlu 151015 CysCysValMetAlaGlyGluLysAlaThrThrValArgLeuValSer 202530 LysMetCysAlaArgGlyAlaTyrLeuPheAspHisMetGlySerPhe 354045 SerArgAlaValLysGluArgLeuLeuGluTrpAspAlaAlaLeuGlu 505560 ProLeuSerPheThrArgThrAspCysArgIleIleArgAspAlaAla 65707580 ArgThrLeuSerCysGlyGlnCysValMetGlyLeuProValValAla 859095 ArgArgGlyAspGluValLeuIleGlyValPheGlnAspValAsnHis 100105110 LeuProProGlyPheValProThrAlaProValValIleArgArgCys 115120125 GlyLysGlyPheLeuGlyValThrLysAlaAlaLeuThrGlyArgAsp 130135140 ProAspLeuHisProGlyAsnValMetValLeuGlyThrAlaThrSer 145150155160 ArgSerMetGlyThrCysLeuAsnGlyLeuLeuPheThrThrPheHis 165170175 GlyAlaSerSerArgThrIleAlaThrProValGlyAlaLeuAsnPro 180185190 ArgTrpTrpSerAlaSerAspAspValThrValTyrProLeuProAsp 195200205 GlyAlaThrSerLeuThrProCysThrCysGlnAlaGluSerCysTrp 210215220 ValIleArgSerAspGlyAlaLeuCysHisGlyLeuSerLysGlyAsp 225230235240 LysValGluLeuAspValAlaMetGluValProAspPheArgGlySer 245250255 SerGlySerProValLeuCysAspGluGlyHisAlaValGlyMetLeu 260265270 ValSerValLeuHisSerGlyGlyArgValThrAlaAlaArgPheThr 275280285 ArgProTrpThrGlnValProThrAspAlaLysThrThrThrGluPro 290295300 ProProValProAlaLysGlyValPheLysGluAlaProLeuPheMet 305310315320 ProThrGlyAlaGlyLysSerThrArgValProLeuGluTyrGlyAsn 325330335 MetGlyHisLysValLeuValLeuAsnProSerValAlaThrValArg 340345350 AlaMetGlyProTyrMetGluArgLeuAlaGlyLysHisProSerIle 355360365 TyrCysGlyHisAspThrThrAlaPheThrArgIleThrAspSerPro 370375380 LeuThrTyrSerThrTyrGlyArgPheLeuAlaAsnProArgGlnMet 385390395400 LeuArgGlyValSerValValIleCysAspGluCysHisSerTyrAsp 405410415 SerThrValLeuLeuGlyIleGlyArgValArgGluLeuAlaArgGly 420425430 CysGlyValGlnLeuValLeuTyrAlaThrAlaThrProProGlySer 435440445 ProMetThrGlnHisProSerIleIleGluThrLysLeuAspValGly 450455460 GluIleProPheTyrGlyHisGlyIleProLeuGluArgMetArgThr 465470475480 GlyArgHisLeuValPheCysHisSerLysAlaGluCysGluArgLeu 485490495 AlaGlyGlnPheSerAlaArgGlyValAsnAlaIleAlaTyrTyrArg 500505510 GlyLysAspSerSerIleIleLysAspGlyAspLeuValValCysAla 515520525 ThrAspAlaLeuSerThrGlyTyrThrGlyAsnPheAspSerValThr 530535540 AspCysGlyLeuValValGluGluValValGluValThrLeuAspPro 545550555560 ThrIleThrIleSerLeuArgThrValProAlaSerAlaGluLeuSer 565570575 MetGlnArgArgGlyArgThrGlyArgGlyArgSerGlyArgTyrTyr 580585590 TyrAlaGlyValGlyLysAlaProAlaGlyValValArgSerGlyPro 595600605 ValTrpSerAlaValGluAlaGlyValThrTrpTyrGlyMetGluPro 610615620 AspLeuThrAlaAsnLeuLeuArgLeuTyrAspAspCysProTyrThr 625630635640 AlaAlaValAlaAlaAspIleGlyGluAlaAlaValPhePheSerGly 645650655 LeuAlaProLeuArgMetHisProAspValSerTrpAlaLysValArg 660665670 GlyValAsnTrpProLeuLeuValGlyValGlnArgThrMetCysArg 675680685 GluThrLeuSerProGlyProSerAspAspProGlnTrpAlaGlyLeu 690695700 LysGlyProAsnProValProLeuLeuLeuArgTrpGlyAsnAspLeu 705710715720 ProSerLysValAlaGlyHisHisIleValAspAspLeuValArgArg 725730735 LeuGlyValAlaGluGlyTyrAlaArgCysAspAlaGlyProIleLeu 740745750 MetIleGlyLeuAlaIleAlaGlyGlyMetIleTyrAlaSerTyrThr 755760765 GlySerLeuValValValThrAspTrpAspValLysGlyGlyGlyAla 770775780 ProLeuTyrArgHisGlyAspGlnAlaThrProGlnProValValGln 785790795800 ValProProValAspHisArgProGlyGlyGluSerAlaProSerAsp 805810815 AlaLysThrValThrAspAlaValAlaAlaIleGlnValAspCysAsp 820825830 TrpThrIleMetThrLeuSerIleGlyGluValLeuSerLeuAlaGln 835840845 AlaLysThrAlaGlu 850 (2) INFORMATION FOR SEQ ID NO:26: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 2561 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: double (D) TOPOLOGY: linear (ii) MOLECULE TYPE: DNA (genomic) (vi) ORIGINAL SOURCE: (C) INDIVIDUAL ISOLATE: HGV DNA contained in vector "LH" (ix) FEATURE: (A) NAME/KEY: CDS (B) LOCATION: 2..2560 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:26: GATCTTGGTGTCCCGGCCCTCGCTGCGGCGTTTGGCTCGGGTGGTT46 IleLeuValSerArgProSerLeuArgArgLeuAlaArgValVal 151015 GAGTGCTGTGTGATGGCGGGTGAGAAGGCCACAACCGTCCGGCTGGTC94 GluCysCysValMetAlaGlyGluLysAlaThrThrValArgLeuVal 202530 TCCAAGATGTGTGCGAGAGGAGCTTATTTGTTCGATTATATGGGCTCA142 SerLysMetCysAlaArgGlyAlaTyrLeuPheAspTyrMetGlySer 354045 TTTTCGCGTGCTGTCAAGGAGCGCCTGTTGGAATGGGACGCGGCTCTT190 PheSerArgAlaValLysGluArgLeuLeuGluTrpAspAlaAlaLeu 505560 GAACCTCTGTCATTCACTAGGACGGACTGTCGCATCATACGGGATGCC238 GluProLeuSerPheThrArgThrAspCysArgIleIleArgAspAla 657075 GCGAGGACTTTGTCCTGCGGGCAATGCGTCATGGGTTTACCCGTGGTT286 AlaArgThrLeuSerCysGlyGlnCysValMetGlyLeuProValVal 80859095 GCGCGCCGTGGTGATGAGGTTCTCATCGGCGTCTTCCAGGATGTGAAT334 AlaArgArgGlyAspGluValLeuIleGlyValPheGlnAspValAsn 100105110 CATTTGCCTCCCGGGTTTGTTCCGACCGCGCCTGTTGTCATCCGACGG382 HisLeuProProGlyPheValProThrAlaProValValIleArgArg 115120125 TGCGGAAAGGGCTTCTTGGGGGTCACAAAGGCTGCCTTGACAGGTCGG430 CysGlyLysGlyPheLeuGlyValThrLysAlaAlaLeuThrGlyArg 130135140 GATCCTGACTTACATCCAGGGAACGTCATGGTGTTGGGGACGGCTACG478 AspProAspLeuHisProGlyAsnValMetValLeuGlyThrAlaThr 145150155 TCGCGAAGCATGGGAACATGCTTGAACGGCCTGCTGTTCACGACCTTC526 SerArgSerMetGlyThrCysLeuAsnGlyLeuLeuPheThrThrPhe 160165170175 CATGGGGCTTCATCCCGAACCATCGCCACACCCGTGGGGGCCCTTAAT574 HisGlyAlaSerSerArgThrIleAlaThrProValGlyAlaLeuAsn 180185190 CCCAGATGGTGGTCAGCCAGTGATGATGTCACGGTGTATCCACTCCCG622 ProArgTrpTrpSerAlaSerAspAspValThrValTyrProLeuPro 195200205 GATGGGGCTACTTCGTTAACGCCTTGTACTTGCCAGGCTGAGTCCTGT670 AspGlyAlaThrSerLeuThrProCysThrCysGlnAlaGluSerCys 210215220 TGGGTCATCAGATCCGACGGGGCCCTATGCCATGGCTTGAGCAAGGGG718 TrpValIleArgSerAspGlyAlaLeuCysHisGlyLeuSerLysGly 225230235 GACAAGGTGGAGCTGGATGTGGCCATGGAGGTCCCTGATTTCCGTGGC766 AspLysValGluLeuAspValAlaMetGluValProAspPheArgGly 240245250255 TCGTCTGGCTCACCGGTCCTATGTGACGAGGGGCACGCAGTAGGAATG814 SerSerGlySerProValLeuCysAspGluGlyHisAlaValGlyMet 260265270 CTCGTGTCTGTGCTTCACTCCGGTGGTAGGGTCACCGCGGCACGGTTC862 LeuValSerValLeuHisSerGlyGlyArgValThrAlaAlaArgPhe 275280285 ACTAGGCCGTGGACCCAAGTGCCAACAGATGCCAAAACCACCACTGAA910 ThrArgProTrpThrGlnValProThrAspAlaLysThrThrThrGlu 290295300 CCCCCTCCGGTGCCGGCCAAAGGAGTTTTCAAAGAGGCCCCGTTGTTT958 ProProProValProAlaLysGlyValPheLysGluAlaProLeuPhe 305310315 ATGCCTACGGGAGCGGGAAAGAGCACTCGCGTCCCGTTGGAGTACGGC1006 MetProThrGlyAlaGlyLysSerThrArgValProLeuGluTyrGly 320325330335 AACATGGGGCACAAGGTCTTAGTCTTGAACCCCTCAGTGGCCACTGTG1054 AsnMetGlyHisLysValLeuValLeuAsnProSerValAlaThrVal 340345350 CGGGCCATGGGCCCGTACATGGAGCGGCTGGCGGGTAAACATCCAAGT1102 ArgAlaMetGlyProTyrMetGluArgLeuAlaGlyLysHisProSer 355360365 ATATACTGTGGGCATGATACAACTGCTTTCACAAGGATCACTGACTCC1150 IleTyrCysGlyHisAspThrThrAlaPheThrArgIleThrAspSer 370375380 CCCCTGACGTATTCAACCTATGGGAGGTTTTTGGCCAACCCTAGGCAG1198 ProLeuThrTyrSerThrTyrGlyArgPheLeuAlaAsnProArgGln 385390395 ATGCTACGGGGCGTTTCGGTGGTCATTTGTGATGAGTGCCACAGTTAT1246 MetLeuArgGlyValSerValValIleCysAspGluCysHisSerTyr 400405410415 GACTCAACCGTGCTGTTAGGCATTGGGAGGGTTCGGGAGCTGGCGCGT1294 AspSerThrValLeuLeuGlyIleGlyArgValArgGluLeuAlaArg 420425430 GGGTGCGGAGTGCAACTAGTGCTCTACGCCACCGCTACGCCTCCCGGA1342 GlyCysGlyValGlnLeuValLeuTyrAlaThrAlaThrProProGly 435440445 TCCCCTATGACGCAGCACCCTTCCATAATTGAGACAAAATTGGACGTG1390 SerProMetThrGlnHisProSerIleIleGluThrLysLeuAspVal 450455460 GGCGAGATTCCCTTTTATGGGCACGGAATACCCCTCGAGCGGATGCGA1438 GlyGluIleProPheTyrGlyHisGlyIleProLeuGluArgMetArg 465470475 ACCGGAAGGCACCTCGTGTTCTGCCATTCTAAGGCTGAGTGCGAGCGC1486 ThrGlyArgHisLeuValPheCysHisSerLysAlaGluCysGluArg 480485490495 CTTGCTGGCCAGTTCTCCGCTAGGGGGGTCAATGCCATTGCCTATTAT1534 LeuAlaGlyGlnPheSerAlaArgGlyValAsnAlaIleAlaTyrTyr 500505510 AGGGGTAAAGACAGTTCTATCATCAAGGATGGGGACCTGGTGGTCTGT1582 ArgGlyLysAspSerSerIleIleLysAspGlyAspLeuValValCys 515520525 GCCACAGACGCGCTTTCCACTGGGTACACTGGAAATTTCGACTCCGTC1630 AlaThrAspAlaLeuSerThrGlyTyrThrGlyAsnPheAspSerVal 530535540 ACCGACTGTGGATTAGTGGTGGAGGAGGTCGTTGAGGTGACCCTTGAT1678 ThrAspCysGlyLeuValValGluGluValValGluValThrLeuAsp 545550555 CCTACCATTACCATCTCCCTGCGGACAGTGCCTGCGTCGGCTGAACTG1726 ProThrIleThrIleSerLeuArgThrValProAlaSerAlaGluLeu 560565570575 TCGATGCAAAGACGAGGACGCACGGGTAGGGGCAGGTCTGGACGCTAC1774 SerMetGlnArgArgGlyArgThrGlyArgGlyArgSerGlyArgTyr 580585590 TACTACGCGGGGGTGGGCAAAGCCCCTGCGGGTGTGGTGCGCTCAGGT1822 TyrTyrAlaGlyValGlyLysAlaProAlaGlyValValArgSerGly 595600605 CCTGTCTGGTCGGCGGTGGAAGCTGGAGTGACCTGGTACGGAATGGAA1870 ProValTrpSerAlaValGluAlaGlyValThrTrpTyrGlyMetGlu 610615620 CCTGACTTGACAGCTAACCTACTGAGACTTTACGACGACTGCCCTTAC1918 ProAspLeuThrAlaAsnLeuLeuArgLeuTyrAspAspCysProTyr 625630635 ACCGCAGCCGTCGCGGCTGATATCGGAGAAGCCGCGGTGTTCTTCTCT1966 ThrAlaAlaValAlaAlaAspIleGlyGluAlaAlaValPhePheSer 640645650655 GGGCTCGCCCCATTGAGGATGCACCCTGATGTCAGCTGGGCAAAAGTT2014 GlyLeuAlaProLeuArgMetHisProAspValSerTrpAlaLysVal 660665670 CGCGGCGTCAACTGGCCCCTCTTGGTGGGTGTTCAGCGGACCATGTGT2062 ArgGlyValAsnTrpProLeuLeuValGlyValGlnArgThrMetCys 675680685 CGGGAAACACTGTCTCCCGGCCCATCGGATGACCCCCAATGGGCAGGT2110 ArgGluThrLeuSerProGlyProSerAspAspProGlnTrpAlaGly 690695700 CTGAAGGGCCCAAATCCTGTCCCACTCCTGCTGAGGTGGGGCAATGAT2158 LeuLysGlyProAsnProValProLeuLeuLeuArgTrpGlyAsnAsp 705710715 TTACCATCTAAAGTGGCCGGCCACCACATAGTGGACGACCTGGTCCGG2206 LeuProSerLysValAlaGlyHisHisIleValAspAspLeuValArg 720725730735 AGACTCGGTGTGGCGGAGGGTTACGCCCGCTGCGACGCTGGGCCGATC2254 ArgLeuGlyValAlaGluGlyTyrAlaArgCysAspAlaGlyProIle 740745750 TTGATGATCGGTCTAGCTATCGCGGGGGGAATGATCTACGCGTCGTAC2302 LeuMetIleGlyLeuAlaIleAlaGlyGlyMetIleTyrAlaSerTyr 755760765 ACCGGGTCGCTAGTGGTGGTGACAGACTGGGATGTGAAGGGGGGTGGC2350 ThrGlySerLeuValValValThrAspTrpAspValLysGlyGlyGly 770775780 GCCCCCCTTTATCGGCATGGAGACCAGGCCACGCCTCAGCCGGTGGTG2398 AlaProLeuTyrArgHisGlyAspGlnAlaThrProGlnProValVal 785790795 CAGGTTCCTCCGGTAGACCATCGGCCGGGGGGTGAATCAGCACCATCG2446 GlnValProProValAspHisArgProGlyGlyGluSerAlaProSer 800805810815 GATGCCAAGACAGTGACAGATGCGGTGGCAGCGATCCAGGTGGACTGC2494 AspAlaLysThrValThrAspAlaValAlaAlaIleGlnValAspCys 820825830 GATTGGACTATCATGACTCTGTCGATCGGAGAAGTGTTGTCCTTGGCT2542 AspTrpThrIleMetThrLeuSerIleGlyGluValLeuSerLeuAla 835840845 CAGGCTAAGACGGCCGAGG2561 GlnAlaLysThrAlaGlu 850 (2) INFORMATION FOR SEQ ID NO:27: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 853 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULE TYPE: protein (xi) SEQUENCE DESCRIPTION: SEQ ID NO:27: IleLeuValSerArgProSerLeuArgArgLeuAlaArgValValGlu 151015 CysCysValMetAlaGlyGluLysAlaThrThrValArgLeuValSer 202530 LysMetCysAlaArgGlyAlaTyrLeuPheAspTyrMetGlySerPhe 354045 SerArgAlaValLysGluArgLeuLeuGluTrpAspAlaAlaLeuGlu 505560 ProLeuSerPheThrArgThrAspCysArgIleIleArgAspAlaAla 65707580 ArgThrLeuSerCysGlyGlnCysValMetGlyLeuProValValAla 859095 ArgArgGlyAspGluValLeuIleGlyValPheGlnAspValAsnHis 100105110 LeuProProGlyPheValProThrAlaProValValIleArgArgCys 115120125 GlyLysGlyPheLeuGlyValThrLysAlaAlaLeuThrGlyArgAsp 130135140 ProAspLeuHisProGlyAsnValMetValLeuGlyThrAlaThrSer 145150155160 ArgSerMetGlyThrCysLeuAsnGlyLeuLeuPheThrThrPheHis 165170175 GlyAlaSerSerArgThrIleAlaThrProValGlyAlaLeuAsnPro 180185190 ArgTrpTrpSerAlaSerAspAspValThrValTyrProLeuProAsp 195200205 GlyAlaThrSerLeuThrProCysThrCysGlnAlaGluSerCysTrp 210215220 ValIleArgSerAspGlyAlaLeuCysHisGlyLeuSerLysGlyAsp 225230235240 LysValGluLeuAspValAlaMetGluValProAspPheArgGlySer 245250255 SerGlySerProValLeuCysAspGluGlyHisAlaValGlyMetLeu 260265270 ValSerValLeuHisSerGlyGlyArgValThrAlaAlaArgPheThr 275280285 ArgProTrpThrGlnValProThrAspAlaLysThrThrThrGluPro 290295300 ProProValProAlaLysGlyValPheLysGluAlaProLeuPheMet 305310315320 ProThrGlyAlaGlyLysSerThrArgValProLeuGluTyrGlyAsn 325330335 MetGlyHisLysValLeuValLeuAsnProSerValAlaThrValArg 340345350 AlaMetGlyProTyrMetGluArgLeuAlaGlyLysHisProSerIle 355360365 TyrCysGlyHisAspThrThrAlaPheThrArgIleThrAspSerPro 370375380 LeuThrTyrSerThrTyrGlyArgPheLeuAlaAsnProArgGlnMet 385390395400 LeuArgGlyValSerValValIleCysAspGluCysHisSerTyrAsp 405410415 SerThrValLeuLeuGlyIleGlyArgValArgGluLeuAlaArgGly 420425430 CysGlyValGlnLeuValLeuTyrAlaThrAlaThrProProGlySer 435440445 ProMetThrGlnHisProSerIleIleGluThrLysLeuAspValGly 450455460 GluIleProPheTyrGlyHisGlyIleProLeuGluArgMetArgThr 465470475480 GlyArgHisLeuValPheCysHisSerLysAlaGluCysGluArgLeu 485490495 AlaGlyGlnPheSerAlaArgGlyValAsnAlaIleAlaTyrTyrArg 500505510 GlyLysAspSerSerIleIleLysAspGlyAspLeuValValCysAla 515520525 ThrAspAlaLeuSerThrGlyTyrThrGlyAsnPheAspSerValThr 530535540 AspCysGlyLeuValValGluGluValValGluValThrLeuAspPro 545550555560 ThrIleThrIleSerLeuArgThrValProAlaSerAlaGluLeuSer 565570575 MetGlnArgArgGlyArgThrGlyArgGlyArgSerGlyArgTyrTyr 580585590 TyrAlaGlyValGlyLysAlaProAlaGlyValValArgSerGlyPro 595600605 ValTrpSerAlaValGluAlaGlyValThrTrpTyrGlyMetGluPro 610615620 AspLeuThrAlaAsnLeuLeuArgLeuTyrAspAspCysProTyrThr 625630635640 AlaAlaValAlaAlaAspIleGlyGluAlaAlaValPhePheSerGly 645650655 LeuAlaProLeuArgMetHisProAspValSerTrpAlaLysValArg 660665670 GlyValAsnTrpProLeuLeuValGlyValGlnArgThrMetCysArg 675680685 GluThrLeuSerProGlyProSerAspAspProGlnTrpAlaGlyLeu 690695700 LysGlyProAsnProValProLeuLeuLeuArgTrpGlyAsnAspLeu 705710715720 ProSerLysValAlaGlyHisHisIleValAspAspLeuValArgArg 725730735 LeuGlyValAlaGluGlyTyrAlaArgCysAspAlaGlyProIleLeu 740745750 MetIleGlyLeuAlaIleAlaGlyGlyMetIleTyrAlaSerTyrThr 755760765 GlySerLeuValValValThrAspTrpAspValLysGlyGlyGlyAla 770775780 ProLeuTyrArgHisGlyAspGlnAlaThrProGlnProValValGln 785790795800 ValProProValAspHisArgProGlyGlyGluSerAlaProSerAsp 805810815 AlaLysThrValThrAspAlaValAlaAlaIleGlnValAspCysAsp 820825830 TrpThrIleMetThrLeuSerIleGlyGluValLeuSerLeuAlaGln 835840845 AlaLysThrAlaGlu 850 (2) INFORMATION FOR SEQ ID NO:28: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 2561 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: double (D) TOPOLOGY: linear (ii) MOLECULE TYPE: DNA (genomic) (vi) ORIGINAL SOURCE: (C) INDIVIDUAL ISOLATE: HGV DNA contained in vector "LC" (ix) FEATURE: (A) NAME/KEY: CDS (B) LOCATION: 2..2560 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:28: GATCTTGGTGTCCCGGCCCTCGCTGCGGCGTTTGGCTCGGGTGGTT46 IleLeuValSerArgProSerLeuArgArgLeuAlaArgValVal 151015 GAGTGCTGTGTGATGGCGGGTGAGAAGGCCACAACCGTCCGGCTGGTC94 GluCysCysValMetAlaGlyGluLysAlaThrThrValArgLeuVal 202530 TCCAAGATGTGTGCGAGAGGAGCTTATTTGTTCGATCATATGGGCTCA142 SerLysMetCysAlaArgGlyAlaTyrLeuPheAspHisMetGlySer 354045 TTTTCGCGTGCTGTCAAGGAGCGCCTGTTGGAATGGGACGCGGCTCTT190 PheSerArgAlaValLysGluArgLeuLeuGluTrpAspAlaAlaLeu 505560 GAACCTCTGTCATTCACTAGGACGGACTGTCGCATCATACGGGATGCC238 GluProLeuSerPheThrArgThrAspCysArgIleIleArgAspAla 657075 GCGAGGACTTTGTCCTTAGGGCAATGCGTCATGGGTTTACCCGTGGTT286 AlaArgThrLeuSerLeuGlyGlnCysValMetGlyLeuProValVal 80859095 GCGCGCCGTGGTGATGAGGTTCTCATCGGCGTCTTCCAGGATGTGAAT334 AlaArgArgGlyAspGluValLeuIleGlyValPheGlnAspValAsn 100105110 CATTTGCCTCCCGGGTTTGTTCCGACCGCGCCTGTTGTCATCCGACGG382 HisLeuProProGlyPheValProThrAlaProValValIleArgArg 115120125 TGCGGAAAGGGCTTCTTGGGGGTCACAAAGGCTGCCTTGACAGGTCGG430 CysGlyLysGlyPheLeuGlyValThrLysAlaAlaLeuThrGlyArg 130135140 GATCCTGACTTACATCCAGGGAACGTCATGGTGTTGGGGACGGCTACG478 AspProAspLeuHisProGlyAsnValMetValLeuGlyThrAlaThr 145150155 TCGCGAAGCATGGGAACATGCTTGAACGGCCTGCTGTTCACGACCTTC526 SerArgSerMetGlyThrCysLeuAsnGlyLeuLeuPheThrThrPhe 160165170175 CATGGGGCTTCATCCCGAACCATCGCCACACCCGTGGGGGCCCTTAAT574 HisGlyAlaSerSerArgThrIleAlaThrProValGlyAlaLeuAsn 180185190 CCCAGATGGTGGTCAGCCAGTGATGATGTCACGGTGTATCCACTCCCG622 ProArgTrpTrpSerAlaSerAspAspValThrValTyrProLeuPro 195200205 GATGGGGCTACTTCGTTAACGCCTTGTACTTGCCAGGCTGAGTCCTGT670 AspGlyAlaThrSerLeuThrProCysThrCysGlnAlaGluSerCys 210215220 TGGGTCATCAGATCCGACGGGGCCCTATGCCATGGCTTGAGCAAGGGG718 TrpValIleArgSerAspGlyAlaLeuCysHisGlyLeuSerLysGly 225230235 GACAAGGTGGAGCTGGATGTGGCCATGGAGGTCCCTGATTTCCGTGGC766 AspLysValGluLeuAspValAlaMetGluValProAspPheArgGly 240245250255 TCGTCTGGCTCACCGGTCCTATGTGACGAGGGGCACGCAGTAGGAATG814 SerSerGlySerProValLeuCysAspGluGlyHisAlaValGlyMet 260265270 CTCGTGTCTGTGCTTCACTCCGGTGGTAGGGTCACCGCGGCACGGTTC862 LeuValSerValLeuHisSerGlyGlyArgValThrAlaAlaArgPhe 275280285 ACTAGGCCGTGGACCCAAGTGCCAACAGATGCCAAAACCACCACTGAA910 ThrArgProTrpThrGlnValProThrAspAlaLysThrThrThrGlu 290295300 CCCCCTCCGGTGCCGGCCAAAGGAGTTTTCAAAGAGGCCCCGTTGTTT958 ProProProValProAlaLysGlyValPheLysGluAlaProLeuPhe 305310315 ATGCCTACGGGAGCGGGAAAGAGCACTCGCGTCCCGTTGGAGTACGGC1006 MetProThrGlyAlaGlyLysSerThrArgValProLeuGluTyrGly 320325330335 AACATGGGGCACAAGGTCTTAGTCTTGAACCCCTCAGTGGCCACTGTG1054 AsnMetGlyHisLysValLeuValLeuAsnProSerValAlaThrVal 340345350 CGGGCCATGGGCCCGTACATGGAGCGGCTGGCGGGTAAACATCCAAGT1102 ArgAlaMetGlyProTyrMetGluArgLeuAlaGlyLysHisProSer 355360365 ATATACTGTGGGCATGATACAACTGCTTTCACAAGGATCACTGACTCC1150 IleTyrCysGlyHisAspThrThrAlaPheThrArgIleThrAspSer 370375380 CCCCTGACGTATTCAACCTATGGGAGGTTTTTGGCCAACCCTAGGCAG1198 ProLeuThrTyrSerThrTyrGlyArgPheLeuAlaAsnProArgGln 385390395 ATGCTACGGGGCGTTTCGGTGGTCATTTGTGATGAGTGCCACAGTTAT1246 MetLeuArgGlyValSerValValIleCysAspGluCysHisSerTyr 400405410415 GACTCAACCGTGCTGTTAGGCATTGGGAGGGTTCGGGAGCTGGCGCGT1294 AspSerThrValLeuLeuGlyIleGlyArgValArgGluLeuAlaArg 420425430 GGGTGCGGAGTGCAACTAGTGCTCTACGCCACCGCTACGCCTCCCGGA1342 GlyCysGlyValGlnLeuValLeuTyrAlaThrAlaThrProProGly 435440445 TCCCCTATGACGCAGCACCCTTCCATAATTGAGACAAAATTGGACGTG1390 SerProMetThrGlnHisProSerIleIleGluThrLysLeuAspVal 450455460 GGCGAGATTCCCTTTTATGGGCACGGAATACCCCTCGAGCGGATGCGA1438 GlyGluIleProPheTyrGlyHisGlyIleProLeuGluArgMetArg 465470475 ACCGGAAGGCACCTCGTGTTCTGCCATTCTAAGGCTGAGTGCGAGCGC1486 ThrGlyArgHisLeuValPheCysHisSerLysAlaGluCysGluArg 480485490495 CTTGCTGGCCAGTTCTCCGCTAGGGGGGTCAATGCCATTGCCTATTAT1534 LeuAlaGlyGlnPheSerAlaArgGlyValAsnAlaIleAlaTyrTyr 500505510 AGGGGTAAAGACAGTTCTATCATCAAGGATGGGGACCTGGTGGTCTGT1582 ArgGlyLysAspSerSerIleIleLysAspGlyAspLeuValValCys 515520525 GCCACAGACGCGCTTTCCACTGGGTACACTGGAAATTTCGACTCCGTC1630 AlaThrAspAlaLeuSerThrGlyTyrThrGlyAsnPheAspSerVal 530535540 ACCGACTGTGGATTAGTGGTGGAGGAGGTCGTTGAGGTGACCCTTGAT1678 ThrAspCysGlyLeuValValGluGluValValGluValThrLeuAsp 545550555 CCTACCATTACCATCTCCCTGCGGACAGTGCCTGCGTCGGCTGAACTG1726 ProThrIleThrIleSerLeuArgThrValProAlaSerAlaGluLeu 560565570575 TCGATGCAAAGACGAGGACGCACGGGTAGGGGCAGGTCTGGACGCTAC1774 SerMetGlnArgArgGlyArgThrGlyArgGlyArgSerGlyArgTyr 580585590 TACTACGCGGGGGTGGGCAAAGCCCCTGCGGGTGTGGTGCGCTCAGGT1822 TyrTyrAlaGlyValGlyLysAlaProAlaGlyValValArgSerGly 595600605 CCTGTCTGGTCGGCGGTGGAAGCTGGAGTGACCTGGTACGGAATGGAA1870 ProValTrpSerAlaValGluAlaGlyValThrTrpTyrGlyMetGlu 610615620 CCTGACTTGACAGCTAACCTACTGAGACTTTACGACGACTGCCCTTAC1918 ProAspLeuThrAlaAsnLeuLeuArgLeuTyrAspAspCysProTyr 625630635 ACCGCAGCCGTCGCGGCTGATATCGGAGAAGCCGCGGTGTTCTTCTCT1966 ThrAlaAlaValAlaAlaAspIleGlyGluAlaAlaValPhePheSer 640645650655 GGGCTCGCCCCATTGAGGATGCACCCTGATGTCAGCTGGGCAAAAGTT2014 GlyLeuAlaProLeuArgMetHisProAspValSerTrpAlaLysVal 660665670 CGCGGCGTCAACTGGCCCCTCTTGGTGGGTGTTCAGCGGACCATGTGT2062 ArgGlyValAsnTrpProLeuLeuValGlyValGlnArgThrMetCys 675680685 CGGGAAACACTGTCTCCCGGCCCATCGGATGACCCCCAATGGGCAGGT2110 ArgGluThrLeuSerProGlyProSerAspAspProGlnTrpAlaGly 690695700 CTGAAGGGCCCAAATCCTGTCCCACTCCTGCTGAGGTGGGGCAATGAT2158 LeuLysGlyProAsnProValProLeuLeuLeuArgTrpGlyAsnAsp 705710715 TTACCATCTAAAGTGGCCGGCCACCACATAGTGGACGACCTGGTCCGG2206 LeuProSerLysValAlaGlyHisHisIleValAspAspLeuValArg 720725730735 AGACTCGGTGTGGCGGAGGGTTACGCCCGCTGCGACGCTGGGCCGATC2254 ArgLeuGlyValAlaGluGlyTyrAlaArgCysAspAlaGlyProIle 740745750 TTGATGATCGGTCTAGCTATCGCGGGGGGAATGATCTACGCGTCGTAC2302 LeuMetIleGlyLeuAlaIleAlaGlyGlyMetIleTyrAlaSerTyr 755760765 ACCGGGTCGCTAGTGGTGGTGACAGACTGGGATGTGAAGGGGGGTGGC2350 ThrGlySerLeuValValValThrAspTrpAspValLysGlyGlyGly 770775780 GCCCCCCTTTATCGGCATGGAGACCAGGCCACGCCTCAGCCGGTGGTG2398 AlaProLeuTyrArgHisGlyAspGlnAlaThrProGlnProValVal 785790795 CAGGTTCCTCCGGTAGACCATCGGCCGGGGGGTGAATCAGCACCATCG2446 GlnValProProValAspHisArgProGlyGlyGluSerAlaProSer 800805810815 GATGCCAAGACAGTGACAGATGCGGTGGCAGCGATCCAGGTGGACTGC2494 AspAlaLysThrValThrAspAlaValAlaAlaIleGlnValAspCys 820825830 GATTGGACTATCATGACTCTGTCGATCGGAGAAGTGTTGTCCTTGGCT2542 AspTrpThrIleMetThrLeuSerIleGlyGluValLeuSerLeuAla 835840845 CAGGCTAAGACGGCCGAGG2561 GlnAlaLysThrAlaGlu 850 (2) INFORMATION FOR SEQ ID NO:29: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 853 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULE TYPE: protein (xi) SEQUENCE DESCRIPTION: SEQ ID NO:29: IleLeuValSerArgProSerLeuArgArgLeuAlaArgValValGlu 151015 CysCysValMetAlaGlyGluLysAlaThrThrValArgLeuValSer 202530 LysMetCysAlaArgGlyAlaTyrLeuPheAspHisMetGlySerPhe 354045 SerArgAlaValLysGluArgLeuLeuGluTrpAspAlaAlaLeuGlu 505560 ProLeuSerPheThrArgThrAspCysArgIleIleArgAspAlaAla 65707580 ArgThrLeuSerLeuGlyGlnCysValMetGlyLeuProValValAla 859095 ArgArgGlyAspGluValLeuIleGlyValPheGlnAspValAsnHis 100105110 LeuProProGlyPheValProThrAlaProValValIleArgArgCys 115120125 GlyLysGlyPheLeuGlyValThrLysAlaAlaLeuThrGlyArgAsp 130135140 ProAspLeuHisProGlyAsnValMetValLeuGlyThrAlaThrSer 145150155160 ArgSerMetGlyThrCysLeuAsnGlyLeuLeuPheThrThrPheHis 165170175 GlyAlaSerSerArgThrIleAlaThrProValGlyAlaLeuAsnPro 180185190 ArgTrpTrpSerAlaSerAspAspValThrValTyrProLeuProAsp 195200205 GlyAlaThrSerLeuThrProCysThrCysGlnAlaGluSerCysTrp 210215220 ValIleArgSerAspGlyAlaLeuCysHisGlyLeuSerLysGlyAsp 225230235240 LysValGluLeuAspValAlaMetGluValProAspPheArgGlySer 245250255 SerGlySerProValLeuCysAspGluGlyHisAlaValGlyMetLeu 260265270 ValSerValLeuHisSerGlyGlyArgValThrAlaAlaArgPheThr 275280285 ArgProTrpThrGlnValProThrAspAlaLysThrThrThrGluPro 290295300 ProProValProAlaLysGlyValPheLysGluAlaProLeuPheMet 305310315320 ProThrGlyAlaGlyLysSerThrArgValProLeuGluTyrGlyAsn 325330335 MetGlyHisLysValLeuValLeuAsnProSerValAlaThrValArg 340345350 AlaMetGlyProTyrMetGluArgLeuAlaGlyLysHisProSerIle 355360365 TyrCysGlyHisAspThrThrAlaPheThrArgIleThrAspSerPro 370375380 LeuThrTyrSerThrTyrGlyArgPheLeuAlaAsnProArgGlnMet 385390395400 LeuArgGlyValSerValValIleCysAspGluCysHisSerTyrAsp 405410415 SerThrValLeuLeuGlyIleGlyArgValArgGluLeuAlaArgGly 420425430 CysGlyValGlnLeuValLeuTyrAlaThrAlaThrProProGlySer 435440445 ProMetThrGlnHisProSerIleIleGluThrLysLeuAspValGly 450455460 GluIleProPheTyrGlyHisGlyIleProLeuGluArgMetArgThr 465470475480 GlyArgHisLeuValPheCysHisSerLysAlaGluCysGluArgLeu 485490495 AlaGlyGlnPheSerAlaArgGlyValAsnAlaIleAlaTyrTyrArg 500505510 GlyLysAspSerSerIleIleLysAspGlyAspLeuValValCysAla 515520525 ThrAspAlaLeuSerThrGlyTyrThrGlyAsnPheAspSerValThr 530535540 AspCysGlyLeuValValGluGluValValGluValThrLeuAspPro 545550555560 ThrIleThrIleSerLeuArgThrValProAlaSerAlaGluLeuSer 565570575 MetGlnArgArgGlyArgThrGlyArgGlyArgSerGlyArgTyrTyr 580585590 TyrAlaGlyValGlyLysAlaProAlaGlyValValArgSerGlyPro 595600605 ValTrpSerAlaValGluAlaGlyValThrTrpTyrGlyMetGluPro 610615620 AspLeuThrAlaAsnLeuLeuArgLeuTyrAspAspCysProTyrThr 625630635640 AlaAlaValAlaAlaAspIleGlyGluAlaAlaValPhePheSerGly 645650655 LeuAlaProLeuArgMetHisProAspValSerTrpAlaLysValArg 660665670 GlyValAsnTrpProLeuLeuValGlyValGlnArgThrMetCysArg 675680685 GluThrLeuSerProGlyProSerAspAspProGlnTrpAlaGlyLeu 690695700 LysGlyProAsnProValProLeuLeuLeuArgTrpGlyAsnAspLeu 705710715720 ProSerLysValAlaGlyHisHisIleValAspAspLeuValArgArg 725730735 LeuGlyValAlaGluGlyTyrAlaArgCysAspAlaGlyProIleLeu 740745750 MetIleGlyLeuAlaIleAlaGlyGlyMetIleTyrAlaSerTyrThr 755760765 GlySerLeuValValValThrAspTrpAspValLysGlyGlyGlyAla 770775780 ProLeuTyrArgHisGlyAspGlnAlaThrProGlnProValValGln 785790795800 ValProProValAspHisArgProGlyGlyGluSerAlaProSerAsp 805810815 AlaLysThrValThrAspAlaValAlaAlaIleGlnValAspCysAsp 820825830 TrpThrIleMetThrLeuSerIleGlyGluValLeuSerLeuAlaGln 835840845 AlaLysThrAlaGlu 850 (2) INFORMATION FOR SEQ ID NO:30: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 2561 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: double (D) TOPOLOGY: linear (ii) MOLECULE TYPE: DNA (genomic) (vi) ORIGINAL SOURCE: (C) INDIVIDUAL ISOLATE: HGV DNA contained in vector "LS" (ix) FEATURE: (A) NAME/KEY: CDS (B) LOCATION: 2..2560 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:30: GATCTTGGTGTCCCGGCCCTCGCTGCGGCGTTTGGCTCGGGTGGTT46 IleLeuValSerArgProSerLeuArgArgLeuAlaArgValVal 151015 GAGTGCTGTGTGATGGCGGGTGAGAAGGCCACAACCGTCCGGCTGGTC94 GluCysCysValMetAlaGlyGluLysAlaThrThrValArgLeuVal 202530 TCCAAGATGTGTGCGAGAGGAGCTTATTTGTTCGATCATATGGGCTCA142 SerLysMetCysAlaArgGlyAlaTyrLeuPheAspHisMetGlySer 354045 TTTTCGCGTGCTGTCAAGGAGCGCCTGTTGGAATGGGACGCGGCTCTT190 PheSerArgAlaValLysGluArgLeuLeuGluTrpAspAlaAlaLeu 505560 GAACCTCTGTCATTCACTAGGACGGACTGTCGCATCATACGGGATGCC238 GluProLeuSerPheThrArgThrAspCysArgIleIleArgAspAla 657075 GCGAGGACTTTGTCCTGCGGGCAATGCGTCATGGGTTTACCCGTGGTT286 AlaArgThrLeuSerCysGlyGlnCysValMetGlyLeuProValVal 80859095 GCGCGCCGTGGTGATGAGGTTCTCATCGGCGTCTTCCAGGATGTGAAT334 AlaArgArgGlyAspGluValLeuIleGlyValPheGlnAspValAsn 100105110 CATTTGCCTCCCGGGTTTGTTCCGACCGCGCCTGTTGTCATCCGACGG382 HisLeuProProGlyPheValProThrAlaProValValIleArgArg 115120125 TGCGGAAAGGGCTTCTTGGGGGTCACAAAGGCTGCCTTGACAGGTCGG430 CysGlyLysGlyPheLeuGlyValThrLysAlaAlaLeuThrGlyArg 130135140 GATCCTGACTTACATCCAGGGAACGTCATGGTGTTGGGGACGGCTACG478 AspProAspLeuHisProGlyAsnValMetValLeuGlyThrAlaThr 145150155 TCGCGAAGCATGGGAACATGCTTGAACGGCCTGCTGTTCACGACCTTC526 SerArgSerMetGlyThrCysLeuAsnGlyLeuLeuPheThrThrPhe 160165170175 CATGGGGCTTCATCCCGAACCATCGCCACACCCGTGGGGGCCCTTAAT574 HisGlyAlaSerSerArgThrIleAlaThrProValGlyAlaLeuAsn 180185190 CCCAGATGGTGGTCAGCCAGTGATGATGTCACGGTGTATCCACTCCCG622 ProArgTrpTrpSerAlaSerAspAspValThrValTyrProLeuPro 195200205 GATGGGGCTACTTCGTTAACGCCTTGTACTTGCCAGGCTGAGTCCTGT670 AspGlyAlaThrSerLeuThrProCysThrCysGlnAlaGluSerCys 210215220 TGGGTCATCAGATCCGACGGGGCCCTATGCCATGGCTTGAGCAAGGGG718 TrpValIleArgSerAspGlyAlaLeuCysHisGlyLeuSerLysGly 225230235 GACAAGGTGGAGCTGGATGTGGCCATGGAGGTCCCTGATTTCCGTGGC766 AspLysValGluLeuAspValAlaMetGluValProAspPheArgGly 240245250255 TCGGCTGGCTCACCGGTCCTATGTGACGAGGGGCACGCAGTAGGAATG814 SerAlaGlySerProValLeuCysAspGluGlyHisAlaValGlyMet 260265270 CTCGTGTCTGTGCTTCACTCCGGTGGTAGGGTCACCGCGGCACGGTTC862 LeuValSerValLeuHisSerGlyGlyArgValThrAlaAlaArgPhe 275280285 ACTAGGCCGTGGACCCAAGTGCCAACAGATGCCAAAACCACCACTGAA910 ThrArgProTrpThrGlnValProThrAspAlaLysThrThrThrGlu 290295300 CCCCCTCCGGTGCCGGCCAAAGGAGTTTTCAAAGAGGCCCCGTTGTTT958 ProProProValProAlaLysGlyValPheLysGluAlaProLeuPhe 305310315 ATGCCTACGGGAGCGGGAAAGAGCACTCGCGTCCCGTTGGAGTACGGC1006 MetProThrGlyAlaGlyLysSerThrArgValProLeuGluTyrGly 320325330335 AACATGGGGCACAAGGTCTTAGTCTTGAACCCCTCAGTGGCCACTGTG1054 AsnMetGlyHisLysValLeuValLeuAsnProSerValAlaThrVal 340345350 CGGGCCATGGGCCCGTACATGGAGCGGCTGGCGGGTAAACATCCAAGT1102 ArgAlaMetGlyProTyrMetGluArgLeuAlaGlyLysHisProSer 355360365 ATATACTGTGGGCATGATACAACTGCTTTCACAAGGATCACTGACTCC1150 IleTyrCysGlyHisAspThrThrAlaPheThrArgIleThrAspSer 370375380 CCCCTGACGTATTCAACCTATGGGAGGTTTTTGGCCAACCCTAGGCAG1198 ProLeuThrTyrSerThrTyrGlyArgPheLeuAlaAsnProArgGln 385390395 ATGCTACGGGGCGTTTCGGTGGTCATTTGTGATGAGTGCCACAGTTAT1246 MetLeuArgGlyValSerValValIleCysAspGluCysHisSerTyr 400405410415 GACTCAACCGTGCTGTTAGGCATTGGGAGGGTTCGGGAGCTGGCGCGT1294 AspSerThrValLeuLeuGlyIleGlyArgValArgGluLeuAlaArg 420425430 GGGTGCGGAGTGCAACTAGTGCTCTACGCCACCGCTACGCCTCCCGGA1342 GlyCysGlyValGlnLeuValLeuTyrAlaThrAlaThrProProGly 435440445 TCCCCTATGACGCAGCACCCTTCCATAATTGAGACAAAATTGGACGTG1390 SerProMetThrGlnHisProSerIleIleGluThrLysLeuAspVal 450455460 GGCGAGATTCCCTTTTATGGGCACGGAATACCCCTCGAGCGGATGCGA1438 GlyGluIleProPheTyrGlyHisGlyIleProLeuGluArgMetArg 465470475 ACCGGAAGGCACCTCGTGTTCTGCCATTCTAAGGCTGAGTGCGAGCGC1486 ThrGlyArgHisLeuValPheCysHisSerLysAlaGluCysGluArg 480485490495 CTTGCTGGCCAGTTCTCCGCTAGGGGGGTCAATGCCATTGCCTATTAT1534 LeuAlaGlyGlnPheSerAlaArgGlyValAsnAlaIleAlaTyrTyr 500505510 AGGGGTAAAGACAGTTCTATCATCAAGGATGGGGACCTGGTGGTCTGT1582 ArgGlyLysAspSerSerIleIleLysAspGlyAspLeuValValCys 515520525 GCCACAGACGCGCTTTCCACTGGGTACACTGGAAATTTCGACTCCGTC1630 AlaThrAspAlaLeuSerThrGlyTyrThrGlyAsnPheAspSerVal 530535540 ACCGACTGTGGATTAGTGGTGGAGGAGGTCGTTGAGGTGACCCTTGAT1678 ThrAspCysGlyLeuValValGluGluValValGluValThrLeuAsp 545550555 CCTACCATTACCATCTCCCTGCGGACAGTGCCTGCGTCGGCTGAACTG1726 ProThrIleThrIleSerLeuArgThrValProAlaSerAlaGluLeu 560565570575 TCGATGCAAAGACGAGGACGCACGGGTAGGGGCAGGTCTGGACGCTAC1774 SerMetGlnArgArgGlyArgThrGlyArgGlyArgSerGlyArgTyr 580585590 TACTACGCGGGGGTGGGCAAAGCCCCTGCGGGTGTGGTGCGCTCAGGT1822 TyrTyrAlaGlyValGlyLysAlaProAlaGlyValValArgSerGly 595600605 CCTGTCTGGTCGGCGGTGGAAGCTGGAGTGACCTGGTACGGAATGGAA1870 ProValTrpSerAlaValGluAlaGlyValThrTrpTyrGlyMetGlu 610615620 CCTGACTTGACAGCTAACCTACTGAGACTTTACGACGACTGCCCTTAC1918 ProAspLeuThrAlaAsnLeuLeuArgLeuTyrAspAspCysProTyr 625630635 ACCGCAGCCGTCGCGGCTGATATCGGAGAAGCCGCGGTGTTCTTCTCT1966 ThrAlaAlaValAlaAlaAspIleGlyGluAlaAlaValPhePheSer 640645650655 GGGCTCGCCCCATTGAGGATGCACCCTGATGTCAGCTGGGCAAAAGTT2014 GlyLeuAlaProLeuArgMetHisProAspValSerTrpAlaLysVal 660665670 CGCGGCGTCAACTGGCCCCTCTTGGTGGGTGTTCAGCGGACCATGTGT2062 ArgGlyValAsnTrpProLeuLeuValGlyValGlnArgThrMetCys 675680685 CGGGAAACACTGTCTCCCGGCCCATCGGATGACCCCCAATGGGCAGGT2110 ArgGluThrLeuSerProGlyProSerAspAspProGlnTrpAlaGly 690695700 CTGAAGGGCCCAAATCCTGTCCCACTCCTGCTGAGGTGGGGCAATGAT2158 LeuLysGlyProAsnProValProLeuLeuLeuArgTrpGlyAsnAsp 705710715 TTACCATCTAAAGTGGCCGGCCACCACATAGTGGACGACCTGGTCCGG2206 LeuProSerLysValAlaGlyHisHisIleValAspAspLeuValArg 720725730735 AGACTCGGTGTGGCGGAGGGTTACGCCCGCTGCGACGCTGGGCCGATC2254 ArgLeuGlyValAlaGluGlyTyrAlaArgCysAspAlaGlyProIle 740745750 TTGATGATCGGTCTAGCTATCGCGGGGGGAATGATCTACGCGTCGTAC2302 LeuMetIleGlyLeuAlaIleAlaGlyGlyMetIleTyrAlaSerTyr 755760765 ACCGGGTCGCTAGTGGTGGTGACAGACTGGGATGTGAAGGGGGGTGGC2350 ThrGlySerLeuValValValThrAspTrpAspValLysGlyGlyGly 770775780 GCCCCCCTTTATCGGCATGGAGACCAGGCCACGCCTCAGCCGGTGGTG2398 AlaProLeuTyrArgHisGlyAspGlnAlaThrProGlnProValVal 785790795 CAGGTTCCTCCGGTAGACCATCGGCCGGGGGGTGAATCAGCACCATCG2446 GlnValProProValAspHisArgProGlyGlyGluSerAlaProSer 800805810815 GATGCCAAGACAGTGACAGATGCGGTGGCAGCGATCCAGGTGGACTGC2494 AspAlaLysThrValThrAspAlaValAlaAlaIleGlnValAspCys 820825830 GATTGGACTATCATGACTCTGTCGATCGGAGAAGTGTTGTCCTTGGCT2542 AspTrpThrIleMetThrLeuSerIleGlyGluValLeuSerLeuAla 835840845 CAGGCTAAGACGGCCGAGG2561 GlnAlaLysThrAlaGlu 850 (2) INFORMATION FOR SEQ ID NO:31: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 853 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULE TYPE: protein (xi) SEQUENCE DESCRIPTION: SEQ ID NO:31: IleLeuValSerArgProSerLeuArgArgLeuAlaArgValValGlu 151015 CysCysValMetAlaGlyGluLysAlaThrThrValArgLeuValSer 202530 LysMetCysAlaArgGlyAlaTyrLeuPheAspHisMetGlySerPhe 354045 SerArgAlaValLysGluArgLeuLeuGluTrpAspAlaAlaLeuGlu 505560 ProLeuSerPheThrArgThrAspCysArgIleIleArgAspAlaAla 65707580 ArgThrLeuSerCysGlyGlnCysValMetGlyLeuProValValAla 859095 ArgArgGlyAspGluValLeuIleGlyValPheGlnAspValAsnHis 100105110 LeuProProGlyPheValProThrAlaProValValIleArgArgCys 115120125 GlyLysGlyPheLeuGlyValThrLysAlaAlaLeuThrGlyArgAsp 130135140 ProAspLeuHisProGlyAsnValMetValLeuGlyThrAlaThrSer 145150155160 ArgSerMetGlyThrCysLeuAsnGlyLeuLeuPheThrThrPheHis 165170175 GlyAlaSerSerArgThrIleAlaThrProValGlyAlaLeuAsnPro 180185190 ArgTrpTrpSerAlaSerAspAspValThrValTyrProLeuProAsp 195200205 GlyAlaThrSerLeuThrProCysThrCysGlnAlaGluSerCysTrp 210215220 ValIleArgSerAspGlyAlaLeuCysHisGlyLeuSerLysGlyAsp 225230235240 LysValGluLeuAspValAlaMetGluValProAspPheArgGlySer 245250255 AlaGlySerProValLeuCysAspGluGlyHisAlaValGlyMetLeu 260265270 ValSerValLeuHisSerGlyGlyArgValThrAlaAlaArgPheThr 275280285 ArgProTrpThrGlnValProThrAspAlaLysThrThrThrGluPro 290295300 ProProValProAlaLysGlyValPheLysGluAlaProLeuPheMet 305310315320 ProThrGlyAlaGlyLysSerThrArgValProLeuGluTyrGlyAsn 325330335 MetGlyHisLysValLeuValLeuAsnProSerValAlaThrValArg 340345350 AlaMetGlyProTyrMetGluArgLeuAlaGlyLysHisProSerIle 355360365 TyrCysGlyHisAspThrThrAlaPheThrArgIleThrAspSerPro 370375380 LeuThrTyrSerThrTyrGlyArgPheLeuAlaAsnProArgGlnMet 385390395400 LeuArgGlyValSerValValIleCysAspGluCysHisSerTyrAsp 405410415 SerThrValLeuLeuGlyIleGlyArgValArgGluLeuAlaArgGly 420425430 CysGlyValGlnLeuValLeuTyrAlaThrAlaThrProProGlySer 435440445 ProMetThrGlnHisProSerIleIleGluThrLysLeuAspValGly 450455460 GluIleProPheTyrGlyHisGlyIleProLeuGluArgMetArgThr 465470475480 GlyArgHisLeuValPheCysHisSerLysAlaGluCysGluArgLeu 485490495 AlaGlyGlnPheSerAlaArgGlyValAsnAlaIleAlaTyrTyrArg 500505510 GlyLysAspSerSerIleIleLysAspGlyAspLeuValValCysAla 515520525 ThrAspAlaLeuSerThrGlyTyrThrGlyAsnPheAspSerValThr 530535540 AspCysGlyLeuValValGluGluValValGluValThrLeuAspPro 545550555560 ThrIleThrIleSerLeuArgThrValProAlaSerAlaGluLeuSer 565570575 MetGlnArgArgGlyArgThrGlyArgGlyArgSerGlyArgTyrTyr 580585590 TyrAlaGlyValGlyLysAlaProAlaGlyValValArgSerGlyPro 595600605 ValTrpSerAlaValGluAlaGlyValThrTrpTyrGlyMetGluPro 610615620 AspLeuThrAlaAsnLeuLeuArgLeuTyrAspAspCysProTyrThr 625630635640 AlaAlaValAlaAlaAspIleGlyGluAlaAlaValPhePheSerGly 645650655 LeuAlaProLeuArgMetHisProAspValSerTrpAlaLysValArg 660665670 GlyValAsnTrpProLeuLeuValGlyValGlnArgThrMetCysArg 675680685 GluThrLeuSerProGlyProSerAspAspProGlnTrpAlaGlyLeu 690695700 LysGlyProAsnProValProLeuLeuLeuArgTrpGlyAsnAspLeu 705710715720 ProSerLysValAlaGlyHisHisIleValAspAspLeuValArgArg 725730735 LeuGlyValAlaGluGlyTyrAlaArgCysAspAlaGlyProIleLeu 740745750 MetIleGlyLeuAlaIleAlaGlyGlyMetIleTyrAlaSerTyrThr 755760765 GlySerLeuValValValThrAspTrpAspValLysGlyGlyGlyAla 770775780 ProLeuTyrArgHisGlyAspGlnAlaThrProGlnProValValGln 785790795800 ValProProValAspHisArgProGlyGlyGluSerAlaProSerAsp 805810815 AlaLysThrValThrAspAlaValAlaAlaIleGlnValAspCysAsp 820825830 TrpThrIleMetThrLeuSerIleGlyGluValLeuSerLeuAlaGln 835840845 AlaLysThrAlaGlu 850 (2) INFORMATION FOR SEQ ID NO:32: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 696 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: double (D) TOPOLOGY: linear (ii) MOLECULE TYPE: DNA (genomic) (vi) ORIGINAL SOURCE: (C) INDIVIDUAL ISOLATE: HGV NS2B (ix) FEATURE: (A) NAME/KEY: CDS (B) LOCATION: 1..696 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:32: GCCGAGTTCTGCTTCGATGCTACATTCGAGGTGGACACTTCGGTGTTG48 AlaGluPheCysPheAspAlaThrPheGluValAspThrSerValLeu 151015 GGCTGGGTGGTGGCCAGTGTGGTAGCTTGGGCCATTGCGCTCCTGAGC96 GlyTrpValValAlaSerValValAlaTrpAlaIleAlaLeuLeuSer 202530 TCGATGAGCGCAGGGGGGTGGAGGCACAAAGCCGTGATCTATAGGACG144 SerMetSerAlaGlyGlyTrpArgHisLysAlaValIleTyrArgThr 354045 TGGTGTAAGGGGTACCAGGCAATCCGTCAAAGGGTGGTGAGGAGCCCC192 TrpCysLysGlyTyrGlnAlaIleArgGlnArgValValArgSerPro 505560 CTCGGGGAGGGGCGGCCTGCCAAACCCCTGACCTTTGCCTGGTGCTTG240 LeuGlyGluGlyArgProAlaLysProLeuThrPheAlaTrpCysLeu 65707580 GCCTCGTACATCTGGCCAGATGCTGTGATGATGGTGGTGGTTGCCTTG288 AlaSerTyrIleTrpProAspAlaValMetMetValValValAlaLeu 859095 GTCCTTCTCTTTGGCCTGTTCGACGCGTTGGATTGGGCCTTGGAGGAG336 ValLeuLeuPheGlyLeuPheAspAlaLeuAspTrpAlaLeuGluGlu 100105110 ATCTTGGTGTCCCGGCCCTCGTTGCGGCGTTTGGCTCGGGTGGTTGAG384 IleLeuValSerArgProSerLeuArgArgLeuAlaArgValValGlu 115120125 TGCTGTGTGATGGCGGGTGAGAAGGCCACAACCGTCCGGCTGGTCTCC432 CysCysValMetAlaGlyGluLysAlaThrThrValArgLeuValSer 130135140 AAGATGTGTGCGAGAGGAGCTTATTTGTTCGATCATATGGGCTCTTTT480 LysMetCysAlaArgGlyAlaTyrLeuPheAspHisMetGlySerPhe 145150155160 TCGCGTGCTGTCAAGGAGCGCCTGTTGGAATGGGACGCAGCTCTTGAA528 SerArgAlaValLysGluArgLeuLeuGluTrpAspAlaAlaLeuGlu 165170175 CCTCTGTCATTCACTAGGACGGACTGTCGCATCATACGGGATGCCGCG576 ProLeuSerPheThrArgThrAspCysArgIleIleArgAspAlaAla 180185190 AGGACTTTGTCCTGCGGGCAGTGCGTCATGGGTTTACCCGTGGTTGCG624 ArgThrLeuSerCysGlyGlnCysValMetGlyLeuProValValAla 195200205 CGCCGTGGTGATGAGGTTCTCATCGGCGTCTTCCAGGATGTGAATCAT672 ArgArgGlyAspGluValLeuIleGlyValPheGlnAspValAsnHis 210215220 TTGCCTCCCGGGTTTGTTCCGACC696 LeuProProGlyPheValProThr 225230 (2) INFORMATION FOR SEQ ID NO:33: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 232 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULE TYPE: protein (xi) SEQUENCE DESCRIPTION: SEQ ID NO:33: AlaGluPheCysPheAspAlaThrPheGluValAspThrSerValLeu 151015 GlyTrpValValAlaSerValValAlaTrpAlaIleAlaLeuLeuSer 202530 SerMetSerAlaGlyGlyTrpArgHisLysAlaValIleTyrArgThr 354045 TrpCysLysGlyTyrGlnAlaIleArgGlnArgValValArgSerPro 505560 LeuGlyGluGlyArgProAlaLysProLeuThrPheAlaTrpCysLeu 65707580 AlaSerTyrIleTrpProAspAlaValMetMetValValValAlaLeu 859095 ValLeuLeuPheGlyLeuPheAspAlaLeuAspTrpAlaLeuGluGlu 100105110 IleLeuValSerArgProSerLeuArgArgLeuAlaArgValValGlu 115120125 CysCysValMetAlaGlyGluLysAlaThrThrValArgLeuValSer 130135140 LysMetCysAlaArgGlyAlaTyrLeuPheAspHisMetGlySerPhe 145150155160 SerArgAlaValLysGluArgLeuLeuGluTrpAspAlaAlaLeuGlu 165170175 ProLeuSerPheThrArgThrAspCysArgIleIleArgAspAlaAla 180185190 ArgThrLeuSerCysGlyGlnCysValMetGlyLeuProValValAla 195200205 ArgArgGlyAspGluValLeuIleGlyValPheGlnAspValAsnHis 210215220 LeuProProGlyPheValProThr 225230 (2) INFORMATION FOR SEQ ID NO:34: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 1848 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: double (D) TOPOLOGY: linear (ii) MOLECULE TYPE: DNA (genomic) (vi) ORIGINAL SOURCE: (C) INDIVIDUAL ISOLATE: HGV NS3 (ix) FEATURE: (A) NAME/KEY: CDS (B) LOCATION: 1..1848 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:34: GCGCCTGTTGTCATCCGACGGTGCGGAAAGGGCTTCTTGGGGGTCACA48 AlaProValValIleArgArgCysGlyLysGlyPheLeuGlyValThr 151015 AAGGCTGCCTTGACAGGTCGGGATCCTGACTTACATCCAGGGAACGTC96 LysAlaAlaLeuThrGlyArgAspProAspLeuHisProGlyAsnVal 202530 ATGGTGTTGGGGACGGCTACGTCGCGAAGCATGGGAACATGCTTGAAC144 MetValLeuGlyThrAlaThrSerArgSerMetGlyThrCysLeuAsn 354045 GGCCTGCTGTTCACGACCTTCCATGGGGCTTCATCCCGAACCATCGCC192 GlyLeuLeuPheThrThrPheHisGlyAlaSerSerArgThrIleAla 505560 ACACCCGTGGGGGCCCTTAATCCCAGATGGTGGTCAGCCAGTGATGAT240 ThrProValGlyAlaLeuAsnProArgTrpTrpSerAlaSerAspAsp 65707580 GTCACGGTGTATCCACTCCCGGATGGGGCTACTTCGTTAACACCTTGT288 ValThrValTyrProLeuProAspGlyAlaThrSerLeuThrProCys 859095 ACTTGCCAGGCTGAGTCCTGTTGGGTCATCAGATCCGACGGGGCCCTA336 ThrCysGlnAlaGluSerCysTrpValIleArgSerAspGlyAlaLeu 100105110 TGCCATGGCTTGAGCAAGGGGGACAAGGTGGAGCTGGATGTGGCCATG384 CysHisGlyLeuSerLysGlyAspLysValGluLeuAspValAlaMet 115120125 GAGGTCTCTGACTTCCGTGGCTCGTCTGGCTCACCGGTCCTATGTGAC432 GluValSerAspPheArgGlySerSerGlySerProValLeuCysAsp 130135140 GAAGGGCACGCAGTAGGAATGCTCGTGTCTGTGCTTCACTCCGGTGGT480 GluGlyHisAlaValGlyMetLeuValSerValLeuHisSerGlyGly 145150155160 AGGGTCACCGCGGCACGGTTCACTAGGCCGTGGACCCAAGTGCCAACA528 ArgValThrAlaAlaArgPheThrArgProTrpThrGlnValProThr 165170175 GATGCCAAAACCACTACTGAACCCCCTCCGGTGCCGGCCAAAGGAGTT576 AspAlaLysThrThrThrGluProProProValProAlaLysGlyVal 180185190 TTCAAAGAGGCCCCGTTGTTTATGCCTACGGGAGCGGGAAAGAGCACT624 PheLysGluAlaProLeuPheMetProThrGlyAlaGlyLysSerThr 195200205 CGCGTCCCGTTGGAGTACGATAACATGGGGCACAAGGTCTTAATCTTG672 ArgValProLeuGluTyrAspAsnMetGlyHisLysValLeuIleLeu 210215220 AACCCCTCAGTGGCCACTGTGCGGGCCATGGGCCCGTACATGGAGCGG720 AsnProSerValAlaThrValArgAlaMetGlyProTyrMetGluArg 225230235240 CTGGCGGGTAAACATCCAAGTATATACTGTGGGCATGATACAACTGCT768 LeuAlaGlyLysHisProSerIleTyrCysGlyHisAspThrThrAla 245250255 TTCACAAGGATCACTGACTCCCCCCTGACGTATTCAACCTATGGGAGG816 PheThrArgIleThrAspSerProLeuThrTyrSerThrTyrGlyArg 260265270 TTTTTGGCCAACCCTAGGCAGATGCTACGGGGCGTTTCGGTGGTCATT864 PheLeuAlaAsnProArgGlnMetLeuArgGlyValSerValValIle 275280285 TGTGATGAGTGCCACAGTCATGACTCAACCGTGCTGTTAGGCATTGGG912 CysAspGluCysHisSerHisAspSerThrValLeuLeuGlyIleGly 290295300 AGAGTCCGGGAGCTGGCGCGTGGGTGCGGGGTGCAACTAGTGCTCTAC960 ArgValArgGluLeuAlaArgGlyCysGlyValGlnLeuValLeuTyr 305310315320 GCCACCGCTACACCTCCCGGATCCCCTATGACGCAGCACCCTTCCATA1008 AlaThrAlaThrProProGlySerProMetThrGlnHisProSerIle 325330335 ATTGAGACAAAATTGGACGTGGGCGAGATTCCCTTTTATGGGCATGGA1056 IleGluThrLysLeuAspValGlyGluIleProPheTyrGlyHisGly 340345350 ATACCCCTCGAGCGGATGCGAACCGGAAGGCACCTCGTGTTCTGCCAT1104 IleProLeuGluArgMetArgThrGlyArgHisLeuValPheCysHis 355360365 TCTAAGGCTGAGTGCGAGCGCCTTGCTGGCCAGTTCTCCGCTAGGGGG1152 SerLysAlaGluCysGluArgLeuAlaGlyGlnPheSerAlaArgGly 370375380 GTCAATGCCATTGCCTATTATAGGGGTAAAGACAGTTCTATCATCAAG1200 ValAsnAlaIleAlaTyrTyrArgGlyLysAspSerSerIleIleLys 385390395400 GATGGGGACCTGGTGGTCTGTGCTACAGACGCGCTTTCCACTGGGTAC1248 AspGlyAspLeuValValCysAlaThrAspAlaLeuSerThrGlyTyr 405410415 ACTGGAAATTTCGACTCCGTCACCGACTGTGGATTAGTGGTGGAGGAG1296 ThrGlyAsnPheAspSerValThrAspCysGlyLeuValValGluGlu 420425430 GTCGTTGAGGTGACCCTTGATCCCACCATTACCATCTCCCTGCGGACA1344 ValValGluValThrLeuAspProThrIleThrIleSerLeuArgThr 435440445 GTGCCTGCGTCGGCTGAACTGTCGATGCAAAGACGAGGACGCACGGGT1392 ValProAlaSerAlaGluLeuSerMetGlnArgArgGlyArgThrGly 450455460 AGGGGCAGGTCTGGACGCTACTACTACGCGGGGGTGGGCAAAGCCCCT1440 ArgGlyArgSerGlyArgTyrTyrTyrAlaGlyValGlyLysAlaPro 465470475480 GCGGGTGTGGTGCGCTCAGGTCCTGTCTGGTCGGCGGTGGAAGCTGGA1488 AlaGlyValValArgSerGlyProValTrpSerAlaValGluAlaGly 485490495 GTGACCTGGTACGGAATGGAACCTGACTTGACAGCTAACCTACTGAGA1536 ValThrTrpTyrGlyMetGluProAspLeuThrAlaAsnLeuLeuArg 500505510 CTTTACGACGACTGCCCTTACACCGCAGCCGTCGCGGCTGATATCGGA1584 LeuTyrAspAspCysProTyrThrAlaAlaValAlaAlaAspIleGly 515520525 GAAGCCGCGGTGTTCTTCTCTGGGCTCGCCCCATTGAGGATGCACCCT1632 GluAlaAlaValPhePheSerGlyLeuAlaProLeuArgMetHisPro 530535540 GATGTCAGCTGGGCAAAAGTTCGCGGCGTCAACTGGCCCCTCTTGGTG1680 AspValSerTrpAlaLysValArgGlyValAsnTrpProLeuLeuVal 545550555560 GGTGTTCAGCGGACCATGTGTCGGGAAACACTGTCTCCCGGCCCATCG1728 GlyValGlnArgThrMetCysArgGluThrLeuSerProGlyProSer 565570575 GATGACCCCCAATGGGCAGGTCTGAAGGGCCCAAATCCTGTCCCACTC1776 AspAspProGlnTrpAlaGlyLeuLysGlyProAsnProValProLeu 580585590 CTGCTGAGGTGGGGCAATGATTTACCATCTAAAGTGGCCGGCCACCAC1824 LeuLeuArgTrpGlyAsnAspLeuProSerLysValAlaGlyHisHis 595600605 ATAGTGGACGACCTGGTCCGGAGA1848 IleValAspAspLeuValArgArg 610615 (2) INFORMATION FOR SEQ ID NO:35: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 616 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULE TYPE: protein (xi) SEQUENCE DESCRIPTION: SEQ ID NO:35: AlaProValValIleArgArgCysGlyLysGlyPheLeuGlyValThr 151015 LysAlaAlaLeuThrGlyArgAspProAspLeuHisProGlyAsnVal 202530 MetValLeuGlyThrAlaThrSerArgSerMetGlyThrCysLeuAsn 354045 GlyLeuLeuPheThrThrPheHisGlyAlaSerSerArgThrIleAla 505560 ThrProValGlyAlaLeuAsnProArgTrpTrpSerAlaSerAspAsp 65707580 ValThrValTyrProLeuProAspGlyAlaThrSerLeuThrProCys 859095 ThrCysGlnAlaGluSerCysTrpValIleArgSerAspGlyAlaLeu 100105110 CysHisGlyLeuSerLysGlyAspLysValGluLeuAspValAlaMet 115120125 GluValSerAspPheArgGlySerSerGlySerProValLeuCysAsp 130135140 GluGlyHisAlaValGlyMetLeuValSerValLeuHisSerGlyGly 145150155160 ArgValThrAlaAlaArgPheThrArgProTrpThrGlnValProThr 165170175 AspAlaLysThrThrThrGluProProProValProAlaLysGlyVal 180185190 PheLysGluAlaProLeuPheMetProThrGlyAlaGlyLysSerThr 195200205 ArgValProLeuGluTyrAspAsnMetGlyHisLysValLeuIleLeu 210215220 AsnProSerValAlaThrValArgAlaMetGlyProTyrMetGluArg 225230235240 LeuAlaGlyLysHisProSerIleTyrCysGlyHisAspThrThrAla 245250255 PheThrArgIleThrAspSerProLeuThrTyrSerThrTyrGlyArg 260265270 PheLeuAlaAsnProArgGlnMetLeuArgGlyValSerValValIle 275280285 CysAspGluCysHisSerHisAspSerThrValLeuLeuGlyIleGly 290295300 ArgValArgGluLeuAlaArgGlyCysGlyValGlnLeuValLeuTyr 305310315320 AlaThrAlaThrProProGlySerProMetThrGlnHisProSerIle 325330335 IleGluThrLysLeuAspValGlyGluIleProPheTyrGlyHisGly 340345350 IleProLeuGluArgMetArgThrGlyArgHisLeuValPheCysHis 355360365 SerLysAlaGluCysGluArgLeuAlaGlyGlnPheSerAlaArgGly 370375380 ValAsnAlaIleAlaTyrTyrArgGlyLysAspSerSerIleIleLys 385390395400 AspGlyAspLeuValValCysAlaThrAspAlaLeuSerThrGlyTyr 405410415 ThrGlyAsnPheAspSerValThrAspCysGlyLeuValValGluGlu 420425430 ValValGluValThrLeuAspProThrIleThrIleSerLeuArgThr 435440445 ValProAlaSerAlaGluLeuSerMetGlnArgArgGlyArgThrGly 450455460 ArgGlyArgSerGlyArgTyrTyrTyrAlaGlyValGlyLysAlaPro 465470475480 AlaGlyValValArgSerGlyProValTrpSerAlaValGluAlaGly 485490495 ValThrTrpTyrGlyMetGluProAspLeuThrAlaAsnLeuLeuArg 500505510 LeuTyrAspAspCysProTyrThrAlaAlaValAlaAlaAspIleGly 515520525 GluAlaAlaValPhePheSerGlyLeuAlaProLeuArgMetHisPro 530535540 AspValSerTrpAlaLysValArgGlyValAsnTrpProLeuLeuVal 545550555560 GlyValGlnArgThrMetCysArgGluThrLeuSerProGlyProSer 565570575 AspAspProGlnTrpAlaGlyLeuLysGlyProAsnProValProLeu 580585590 LeuLeuArgTrpGlyAsnAspLeuProSerLysValAlaGlyHisHis 595600605 IleValAspAspLeuValArgArg 610615 (2) INFORMATION FOR SEQ ID NO:36: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 1071 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: double (D) TOPOLOGY: linear (ii) MOLECULE TYPE: DNA (genomic) (vi) ORIGINAL SOURCE: (C) INDIVIDUAL ISOLATE: HGV NS4A- B (ix) FEATURE: (A) NAME/KEY: CDS (B) LOCATION: 1..1071 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:36: CTCGGTGTGGCGGAGGGTTACGTCCGCTGCGACGCTGGGCCGATCTTG48 LeuGlyValAlaGluGlyTyrValArgCysAspAlaGlyProIleLeu 151015 ATGATCGGTCTAGCTATCGCGGGGGGAATGATCTACGCGTCATACACC96 MetIleGlyLeuAlaIleAlaGlyGlyMetIleTyrAlaSerTyrThr 202530 GGGTCGCTAGTGGTGGTGACAGACTGGGATGTGAAGGGGGGTGGCGCC144 GlySerLeuValValValThrAspTrpAspValLysGlyGlyGlyAla 354045 CCCCTTTATCGGCATGGAGACCAGGCCACGCCTCAGCCGGTGGTGCAG192 ProLeuTyrArgHisGlyAspGlnAlaThrProGlnProValValGln 505560 GTTCCTCCGGTAGACCATCGGCCGGGGGGTGAATCAGCACCATCGGAT240 ValProProValAspHisArgProGlyGlyGluSerAlaProSerAsp 65707580 GCCAAGACAGTGACAGATGCGGTGGCAGCCATCCAGGTGGACTGCGAT288 AlaLysThrValThrAspAlaValAlaAlaIleGlnValAspCysAsp 859095 TGGACTATCATGACTCTGTCGATCGGAGAAGTGTTGTCCTTGGCTCAG336 TrpThrIleMetThrLeuSerIleGlyGluValLeuSerLeuAlaGln 100105110 GCTAAGACGGCCGAGGCCTACACAGCAACCGCCAAGTGGCTCGCTGGC384 AlaLysThrAlaGluAlaTyrThrAlaThrAlaLysTrpLeuAlaGly 115120125 TGCTATACGGGGACGCGGGCCGTTCCCACTGTATCCATTGTTGACAAG432 CysTyrThrGlyThrArgAlaValProThrValSerIleValAspLys 130135140 CTCTTCGCCGGAGGGTGGGCGGCTGTGGTGGGCCATTGCCACAGCGTG480 LeuPheAlaGlyGlyTrpAlaAlaValValGlyHisCysHisSerVal 145150155160 ATTGCTGCGGCGGTGGCGGCCTACGGGGCTTCAAGGAGCCCGCCGTTG528 IleAlaAlaAlaValAlaAlaTyrGlyAlaSerArgSerProProLeu 165170175 GCAGCCGCGGCTTCCTACCTGATGGGGTTGGGCGTTGGAGGCAACGCT576 AlaAlaAlaAlaSerTyrLeuMetGlyLeuGlyValGlyGlyAsnAla 180185190 CAGACGCGCCTGGCGTCTGCCCTCCTATTGGGGGCTGCTGGAACCGCC624 GlnThrArgLeuAlaSerAlaLeuLeuLeuGlyAlaAlaGlyThrAla 195200205 TTGGGCACTCCTGTCGTGGGCTTGACCATGGCAGGTGCGTTCATGGGG672 LeuGlyThrProValValGlyLeuThrMetAlaGlyAlaPheMetGly 210215220 GGGGCCAGTGTCTCCCCCTCCTTGGTCACCATTTTATTGGGGGCCGTC720 GlyAlaSerValSerProSerLeuValThrIleLeuLeuGlyAlaVal 225230235240 GGAGGTTGGGAGGGTGTTGTCAACGCGGCGAGCCTAGTCTTTGACTTC768 GlyGlyTrpGluGlyValValAsnAlaAlaSerLeuValPheAspPhe 245250255 ATGGCGGGGAAACTTTCATCAGAAGATCTGTGGTATGCCATCCCGGTA816 MetAlaGlyLysLeuSerSerGluAspLeuTrpTyrAlaIleProVal 260265270 CTGACCAGCCCGGGGGCGGGCCTTGCGGGGATCGCTCTCGGGTTGGTT864 LeuThrSerProGlyAlaGlyLeuAlaGlyIleAlaLeuGlyLeuVal 275280285 TTGTATTCAGCTAACAACTCTGGCACTACCACTTGGTTGAACCGTCTG912 LeuTyrSerAlaAsnAsnSerGlyThrThrThrTrpLeuAsnArgLeu 290295300 CTGACTACGTTACCAAGGTCTTCATGTATCCCGGACAGTTACTTTCAG960 LeuThrThrLeuProArgSerSerCysIleProAspSerTyrPheGln 305310315320 CAAGTTGACTATTGCGACAAGGTCTCAGCCGTGCTCCGGCGCCTGAGC1008 GlnValAspTyrCysAspLysValSerAlaValLeuArgArgLeuSer 325330335 CTCACCCGCACAGTGGTTGCCCTGGTCAACAGGGAGCCTAAGGTGGAT1056 LeuThrArgThrValValAlaLeuValAsnArgGluProLysValAsp 340345350 GAGGTACAGGTGGGG1071 GluValGlnValGly 355 (2) INFORMATION FOR SEQ ID NO:37: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 357 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULE TYPE: protein (xi) SEQUENCE DESCRIPTION: SEQ ID NO:37: LeuGlyValAlaGluGlyTyrValArgCysAspAlaGlyProIleLeu 151015 MetIleGlyLeuAlaIleAlaGlyGlyMetIleTyrAlaSerTyrThr 202530 GlySerLeuValValValThrAspTrpAspValLysGlyGlyGlyAla 354045 ProLeuTyrArgHisGlyAspGlnAlaThrProGlnProValValGln 505560 ValProProValAspHisArgProGlyGlyGluSerAlaProSerAsp 65707580 AlaLysThrValThrAspAlaValAlaAlaIleGlnValAspCysAsp 859095 TrpThrIleMetThrLeuSerIleGlyGluValLeuSerLeuAlaGln 100105110 AlaLysThrAlaGluAlaTyrThrAlaThrAlaLysTrpLeuAlaGly 115120125 CysTyrThrGlyThrArgAlaValProThrValSerIleValAspLys 130135140 LeuPheAlaGlyGlyTrpAlaAlaValValGlyHisCysHisSerVal 145150155160 IleAlaAlaAlaValAlaAlaTyrGlyAlaSerArgSerProProLeu 165170175 AlaAlaAlaAlaSerTyrLeuMetGlyLeuGlyValGlyGlyAsnAla 180185190 GlnThrArgLeuAlaSerAlaLeuLeuLeuGlyAlaAlaGlyThrAla 195200205 LeuGlyThrProValValGlyLeuThrMetAlaGlyAlaPheMetGly 210215220 GlyAlaSerValSerProSerLeuValThrIleLeuLeuGlyAlaVal 225230235240 GlyGlyTrpGluGlyValValAsnAlaAlaSerLeuValPheAspPhe 245250255 MetAlaGlyLysLeuSerSerGluAspLeuTrpTyrAlaIleProVal 260265270 LeuThrSerProGlyAlaGlyLeuAlaGlyIleAlaLeuGlyLeuVal 275280285 LeuTyrSerAlaAsnAsnSerGlyThrThrThrTrpLeuAsnArgLeu 290295300 LeuThrThrLeuProArgSerSerCysIleProAspSerTyrPheGln 305310315320 GlnValAspTyrCysAspLysValSerAlaValLeuArgArgLeuSer 325330335 LeuThrArgThrValValAlaLeuValAsnArgGluProLysValAsp 340345350 GluValGlnValGly 355 (2) INFORMATION FOR SEQ ID NO:38: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 1377 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: double (D) TOPOLOGY: linear (ii) MOLECULE TYPE: DNA (genomic) (vi) ORIGINAL SOURCE: (C) INDIVIDUAL ISOLATE: HGV NS5A (ix) FEATURE: (A) NAME/KEY: CDS (B) LOCATION: 1..1377 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:38: TATGTCTGGGACCTGTGGGAGTGGATCATGCGCCAAGTGCGCGTGGTC48 TyrValTrpAspLeuTrpGluTrpIleMetArgGlnValArgValVal 151015 ATGGCCAGACTCAGGGCCCTCTGCCCCGTGGTGTCACTACCCTTGTGG96 MetAlaArgLeuArgAlaLeuCysProValValSerLeuProLeuTrp 202530 CATTGCGGGGAGGGGTGGTCCGGGGAATGGTTGCTTGACGGTCATGTT144 HisCysGlyGluGlyTrpSerGlyGluTrpLeuLeuAspGlyHisVal 354045 GAGAGTCGCTGCCTCTGTGGCTGCGTGATCACTGGTGACGTTCTGAAT192 GluSerArgCysLeuCysGlyCysValIleThrGlyAspValLeuAsn 505560 GGGCAACTCAAAGAACCAGTTTACTCTACCAAGCTGTGCCGGCACTAT240 GlyGlnLeuLysGluProValTyrSerThrLysLeuCysArgHisTyr 65707580 TGGATGGGGACTGTCCCTGTGAACATGCTGGGTTACGGTGAAACGTCG288 TrpMetGlyThrValProValAsnMetLeuGlyTyrGlyGluThrSer 859095 CCTCTCCTGGCCTCCGACACCCCGAAGGTTGTGCCCTTCGGGACGTCT336 ProLeuLeuAlaSerAspThrProLysValValProPheGlyThrSer 100105110 GGCTGGGCTGAGGTGGTGGTGACCACTACCCACGTGGTAATCAGGAGG384 GlyTrpAlaGluValValValThrThrThrHisValValIleArgArg 115120125 ACCTCCGCCTATAAGCTGCTGCGCCAGCAAATCCTATCGGCTGCTGTA432 ThrSerAlaTyrLysLeuLeuArgGlnGlnIleLeuSerAlaAlaVal 130135140 GCTGAGCCCTACTACGTCGACGGCATTCCGGTCTCATGGGACGCGGAC480 AlaGluProTyrTyrValAspGlyIleProValSerTrpAspAlaAsp 145150155160 GCTCGTGCGCCCGCCATGGTCTATGGCCCTGGGCAAAGTGTTACCATT528 AlaArgAlaProAlaMetValTyrGlyProGlyGlnSerValThrIle 165170175 GACGGGGAGCGCTACACCTTGCCTCATCAACTGAGGCTCAGGAATGTG576 AspGlyGluArgTyrThrLeuProHisGlnLeuArgLeuArgAsnVal 180185190 GCACCCTCTGAGGTTTCATCCGAGGTGTCCATTGACATTGGGACGGAG624 AlaProSerGluValSerSerGluValSerIleAspIleGlyThrGlu 195200205 ACTGAAGACTCAGAACTGACTGAGGCCGATCTGCCGCCGGCGGCTGCT672 ThrGluAspSerGluLeuThrGluAlaAspLeuProProAlaAlaAla 210215220 GCTCTCCAAGCGATCGAGAATGCTGCGAGGATTCTTGAACCGCACATT720 AlaLeuGlnAlaIleGluAsnAlaAlaArgIleLeuGluProHisIle 225230235240 GATGTCATCATGGAGGACTGCAGTACACCCTCTCTTTGTGGTAGTAGC768 AspValIleMetGluAspCysSerThrProSerLeuCysGlySerSer 245250255 CGAGAGATGCCTGTATGGGGAGAAGACATCCCCCGTACTCCATCGCCA816 ArgGluMetProValTrpGlyGluAspIleProArgThrProSerPro 260265270 GCACTTATCTCGGTTACTGAGAGCAGCTCAGATGAGAAGACCCCGTCG864 AlaLeuIleSerValThrGluSerSerSerAspGluLysThrProSer 275280285 GTGTCCTCCTCGCAGGAGGATACCCCGTCCTCTGACTCATTCGAGGTC912 ValSerSerSerGlnGluAspThrProSerSerAspSerPheGluVal 290295300 ATCCAAGAGTCCGAGACAGCCGAAGGGGAGGAAAGTGTCTTCAACGTG960 IleGlnGluSerGluThrAlaGluGlyGluGluSerValPheAsnVal 305310315320 GCTCTTTCCGTATTAAAAGCCTTATTTCCACAGAGCGACGCGACCAGG1008 AlaLeuSerValLeuLysAlaLeuPheProGlnSerAspAlaThrArg 325330335 AAGCTTACCGTCAAGATGTCGTGCTGCGTTGAAAAGAGCGTCACGCGC1056 LysLeuThrValLysMetSerCysCysValGluLysSerValThrArg 340345350 TTTTTCTCATTGGGGTTGACGGTGGCTGATGTTGCTAGCCTGTGTGAG1104 PhePheSerLeuGlyLeuThrValAlaAspValAlaSerLeuCysGlu 355360365 ATGGAAATCCAGAACCATACAGCCTATTGTGACCAGGTGCGCACTCCG1152 MetGluIleGlnAsnHisThrAlaTyrCysAspGlnValArgThrPro 370375380 CTTGAATTGCAGGTTGGGTGCTTGGTGGGCAATGAACTTACCTTTGAA1200 LeuGluLeuGlnValGlyCysLeuValGlyAsnGluLeuThrPheGlu 385390395400 TGTGACAAGTGTGAGGCTAGGCAAGAAACCTTGGCCTCCTTCTCTTAC1248 CysAspLysCysGluAlaArgGlnGluThrLeuAlaSerPheSerTyr 405410415 ATTTGGTCTGGAGTGCCGCTGACTAGGGCCACGCCGGCCAAGCCTCCC1296 IleTrpSerGlyValProLeuThrArgAlaThrProAlaLysProPro 420425430 GTGGTGAGGCCGGTTGGCTCTTTGTTAGTGGCCGACACTACTAAGGTG1344 ValValArgProValGlySerLeuLeuValAlaAspThrThrLysVal 435440445 TATGTTACCAATCCAGACAATGTGGGACGGAGG1377 TyrValThrAsnProAspAsnValGlyArgArg 450455 (2) INFORMATION FOR SEQ ID NO:39: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 459 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULE TYPE: protein (xi) SEQUENCE DESCRIPTION: SEQ ID NO:39: TyrValTrpAspLeuTrpGluTrpIleMetArgGlnValArgValVal 151015 MetAlaArgLeuArgAlaLeuCysProValValSerLeuProLeuTrp 202530 HisCysGlyGluGlyTrpSerGlyGluTrpLeuLeuAspGlyHisVal 354045 GluSerArgCysLeuCysGlyCysValIleThrGlyAspValLeuAsn 505560 GlyGlnLeuLysGluProValTyrSerThrLysLeuCysArgHisTyr 65707580 TrpMetGlyThrValProValAsnMetLeuGlyTyrGlyGluThrSer 859095 ProLeuLeuAlaSerAspThrProLysValValProPheGlyThrSer 100105110 GlyTrpAlaGluValValValThrThrThrHisValValIleArgArg 115120125 ThrSerAlaTyrLysLeuLeuArgGlnGlnIleLeuSerAlaAlaVal 130135140 AlaGluProTyrTyrValAspGlyIleProValSerTrpAspAlaAsp 145150155160 AlaArgAlaProAlaMetValTyrGlyProGlyGlnSerValThrIle 165170175 AspGlyGluArgTyrThrLeuProHisGlnLeuArgLeuArgAsnVal 180185190 AlaProSerGluValSerSerGluValSerIleAspIleGlyThrGlu 195200205 ThrGluAspSerGluLeuThrGluAlaAspLeuProProAlaAlaAla 210215220 AlaLeuGlnAlaIleGluAsnAlaAlaArgIleLeuGluProHisIle 225230235240 AspValIleMetGluAspCysSerThrProSerLeuCysGlySerSer 245250255 ArgGluMetProValTrpGlyGluAspIleProArgThrProSerPro 260265270 AlaLeuIleSerValThrGluSerSerSerAspGluLysThrProSer 275280285 ValSerSerSerGlnGluAspThrProSerSerAspSerPheGluVal 290295300 IleGlnGluSerGluThrAlaGluGlyGluGluSerValPheAsnVal 305310315320 AlaLeuSerValLeuLysAlaLeuPheProGlnSerAspAlaThrArg 325330335 LysLeuThrValLysMetSerCysCysValGluLysSerValThrArg 340345350 PhePheSerLeuGlyLeuThrValAlaAspValAlaSerLeuCysGlu 355360365 MetGluIleGlnAsnHisThrAlaTyrCysAspGlnValArgThrPro 370375380 LeuGluLeuGlnValGlyCysLeuValGlyAsnGluLeuThrPheGlu 385390395400 CysAspLysCysGluAlaArgGlnGluThrLeuAlaSerPheSerTyr 405410415 IleTrpSerGlyValProLeuThrArgAlaThrProAlaLysProPro 420425430 ValValArgProValGlySerLeuLeuValAlaAspThrThrLysVal 435440445 TyrValThrAsnProAspAsnValGlyArgArg 450455 (2) INFORMATION FOR SEQ ID NO:40: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 1548 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: double (D) TOPOLOGY: linear (ii) MOLECULE TYPE: DNA (genomic) (vi) ORIGINAL SOURCE: (C) INDIVIDUAL ISOLATE: HGV NS5B (ix) FEATURE: (A) NAME/KEY: CDS (B) LOCATION: 1..1548 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:40: GTGGACAAGGTGACCTTCTGGCGTGCTCCTAGGGTTCATGATAAGTAC48 ValAspLysValThrPheTrpArgAlaProArgValHisAspLysTyr 151015 CTCGTGGACTCTATTGAGCGCGCTAAGAGGGCCGCTCAAGCCTGCCTA96 LeuValAspSerIleGluArgAlaLysArgAlaAlaGlnAlaCysLeu 202530 AGCATGGGTTACACTTATGAGGAAGCAATAAGGACTGTAAGGCCACAT144 SerMetGlyTyrThrTyrGluGluAlaIleArgThrValArgProHis 354045 GCTGCCATGGGCTGGGGATCTAAGGTGTCGGTTAAGGACTTAGCCACC192 AlaAlaMetGlyTrpGlySerLysValSerValLysAspLeuAlaThr 505560 CCCGCGGGGAAGATGGCCGTCCATGACCGGCTTCAGGAGATACTTGAA240 ProAlaGlyLysMetAlaValHisAspArgLeuGlnGluIleLeuGlu 65707580 GGGACTCCGGTCCCCTTTACTCTTACTGTGAAAAAGGAGGTGTTCTTC288 GlyThrProValProPheThrLeuThrValLysLysGluValPhePhe 859095 AAAGACCGGAAGGAGGAGAAGGCCCCCCGCCTCATTGTGTTCCCCCCC336 LysAspArgLysGluGluLysAlaProArgLeuIleValPheProPro 100105110 CTGGACTTCCGGATAGCTGAAAAGCTCATCTTGGGAGACCCAGGCCGG384 LeuAspPheArgIleAlaGluLysLeuIleLeuGlyAspProGlyArg 115120125 GTAGCCAAGGCGGTGTTGGGGGGGGCCTACGCCTTCCAGTACACCCCA432 ValAlaLysAlaValLeuGlyGlyAlaTyrAlaPheGlnTyrThrPro 130135140 AATCAGCGAGTTAAGGAGATGCTCAAGCTATGGGAGTCTAAGAAGACC480 AsnGlnArgValLysGluMetLeuLysLeuTrpGluSerLysLysThr 145150155160 CCTTGCGCCATCTGTGTGGACGCCACCTGCTTCGACAGTAGCATAACT528 ProCysAlaIleCysValAspAlaThrCysPheAspSerSerIleThr 165170175 GAAGAGGACGTGGCTTTGGAGACAGAGCTATACGCTCTGGCCTCTGAC576 GluGluAspValAlaLeuGluThrGluLeuTyrAlaLeuAlaSerAsp 180185190 CATCCAGAATGGGTGCGGGCACTTGGGAAATACTATGCCTCAGGCACC624 HisProGluTrpValArgAlaLeuGlyLysTyrTyrAlaSerGlyThr 195200205 ATGGTCACCCCGGAAGGGGTGCCCGTCGGTGAGAGGTATTGCAGATCC672 MetValThrProGluGlyValProValGlyGluArgTyrCysArgSer 210215220 TCGGGTGTCCTAACAACTAGCGCGAGCAACTGCTTGACCTGCTACATC720 SerGlyValLeuThrThrSerAlaSerAsnCysLeuThrCysTyrIle 225230235240 AAGGTGAAAGCTGCCTGTGAGAGAGTGGGGCTGAAAAATGTCTCTCTT768 LysValLysAlaAlaCysGluArgValGlyLeuLysAsnValSerLeu 245250255 CTCATAGCCGGCGATGACTGCTTGATCATATGTGAGCGGCCAGTGTGC816 LeuIleAlaGlyAspAspCysLeuIleIleCysGluArgProValCys 260265270 GACCCAAGCGACGCTTTGGGCAGAGCCCTAGCGAGCTATGGGTACGCG864 AspProSerAspAlaLeuGlyArgAlaLeuAlaSerTyrGlyTyrAla 275280285 TGCGAGCCCTCATATCATGCATCATTGGACACGGCCCCCTTCTGCTCC912 CysGluProSerTyrHisAlaSerLeuAspThrAlaProPheCysSer 290295300 ACTTGGCTTGCTGAGTGCAATGCAGATGGGAAGCGCCATTTCTTCCTG960 ThrTrpLeuAlaGluCysAsnAlaAspGlyLysArgHisPhePheLeu 305310315320 ACCACGGACTTCCGGAGGCCGCTCGCTCGCATGTCGAGTGAGTATAGT1008 ThrThrAspPheArgArgProLeuAlaArgMetSerSerGluTyrSer 325330335 GACCCGATGGCTTCGGCGATCGGTTACATCCTCCTTTATCCTTGGCAC1056 AspProMetAlaSerAlaIleGlyTyrIleLeuLeuTyrProTrpHis 340345350 CCCATCACACGGTGGGTCATCATCCCTCATGTGCTAACGTGCGCATTC1104 ProIleThrArgTrpValIleIleProHisValLeuThrCysAlaPhe 355360365 AGGGGTGGAGGCACACCGTCTGATCCGGTTTGGTGCCAGGTGCATGGT1152 ArgGlyGlyGlyThrProSerAspProValTrpCysGlnValHisGly 370375380 AACTACTACAAGTTTCCACTGGACAAACTGCCTAACATCATCGTGGCC1200 AsnTyrTyrLysPheProLeuAspLysLeuProAsnIleIleValAla 385390395400 CTCCACGGACCAGCAGCGTTGAGGGTTACCGCAGACACAACTAAAACA1248 LeuHisGlyProAlaAlaLeuArgValThrAlaAspThrThrLysThr 405410415 AAGATGGAGGCTGGTAAGGTTCTGAGCGACCTCAAGCTCCCTGGCTTA1296 LysMetGluAlaGlyLysValLeuSerAspLeuLysLeuProGlyLeu 420425430 GCAGTCCACCGAAAGAAGGCCGGGGCGTTGCGAACACGCATGCTCCGC1344 AlaValHisArgLysLysAlaGlyAlaLeuArgThrArgMetLeuArg 435440445 TCGCGCGGTTGGGCTGAGTTGGCTAGGGGCTTGTTGTGGCATCCAGGC1392 SerArgGlyTrpAlaGluLeuAlaArgGlyLeuLeuTrpHisProGly 450455460 CTACGGCTTCCTCCCCCTGAGATTGCTGGTATCCCGGGGGGTTTCCCT1440 LeuArgLeuProProProGluIleAlaGlyIleProGlyGlyPhePro 465470475480 CTCTCCCCCCCCTATATGGGGGTGGTACATCAATTGGATTTCACAAGC1488 LeuSerProProTyrMetGlyValValHisGlnLeuAspPheThrSer 485490495 CAGAGGAGTCGCTGGCGGTGGTTGGGGTTCTTAGCCCTGCTCATCGTA1536 GlnArgSerArgTrpArgTrpLeuGlyPheLeuAlaLeuLeuIleVal 500505510 GCCCTCTTCGGG1548 AlaLeuPheGly 515 (2) INFORMATION FOR SEQ ID NO:41: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 516 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULE TYPE: protein (xi) SEQUENCE DESCRIPTION: SEQ ID NO:41: ValAspLysValThrPheTrpArgAlaProArgValHisAspLysTyr 151015 LeuValAspSerIleGluArgAlaLysArgAlaAlaGlnAlaCysLeu 202530 SerMetGlyTyrThrTyrGluGluAlaIleArgThrValArgProHis 354045 AlaAlaMetGlyTrpGlySerLysValSerValLysAspLeuAlaThr 505560 ProAlaGlyLysMetAlaValHisAspArgLeuGlnGluIleLeuGlu 65707580 GlyThrProValProPheThrLeuThrValLysLysGluValPhePhe 859095 LysAspArgLysGluGluLysAlaProArgLeuIleValPheProPro 100105110 LeuAspPheArgIleAlaGluLysLeuIleLeuGlyAspProGlyArg 115120125 ValAlaLysAlaValLeuGlyGlyAlaTyrAlaPheGlnTyrThrPro 130135140 AsnGlnArgValLysGluMetLeuLysLeuTrpGluSerLysLysThr 145150155160 ProCysAlaIleCysValAspAlaThrCysPheAspSerSerIleThr 165170175 GluGluAspValAlaLeuGluThrGluLeuTyrAlaLeuAlaSerAsp 180185190 HisProGluTrpValArgAlaLeuGlyLysTyrTyrAlaSerGlyThr 195200205 MetValThrProGluGlyValProValGlyGluArgTyrCysArgSer 210215220 SerGlyValLeuThrThrSerAlaSerAsnCysLeuThrCysTyrIle 225230235240 LysValLysAlaAlaCysGluArgValGlyLeuLysAsnValSerLeu 245250255 LeuIleAlaGlyAspAspCysLeuIleIleCysGluArgProValCys 260265270 AspProSerAspAlaLeuGlyArgAlaLeuAlaSerTyrGlyTyrAla 275280285 CysGluProSerTyrHisAlaSerLeuAspThrAlaProPheCysSer 290295300 ThrTrpLeuAlaGluCysAsnAlaAspGlyLysArgHisPhePheLeu 305310315320 ThrThrAspPheArgArgProLeuAlaArgMetSerSerGluTyrSer 325330335 AspProMetAlaSerAlaIleGlyTyrIleLeuLeuTyrProTrpHis 340345350 ProIleThrArgTrpValIleIleProHisValLeuThrCysAlaPhe 355360365 ArgGlyGlyGlyThrProSerAspProValTrpCysGlnValHisGly 370375380 AsnTyrTyrLysPheProLeuAspLysLeuProAsnIleIleValAla 385390395400 LeuHisGlyProAlaAlaLeuArgValThrAlaAspThrThrLysThr 405410415 LysMetGluAlaGlyLysValLeuSerAspLeuLysLeuProGlyLeu 420425430 AlaValHisArgLysLysAlaGlyAlaLeuArgThrArgMetLeuArg 435440445 SerArgGlyTrpAlaGluLeuAlaArgGlyLeuLeuTrpHisProGly 450455460 LeuArgLeuProProProGluIleAlaGlyIleProGlyGlyPhePro 465470475480 LeuSerProProTyrMetGlyValValHisGlnLeuAspPheThrSer 485490495 GlnArgSerArgTrpArgTrpLeuGlyPheLeuAlaLeuLeuIleVal 500505510 AlaLeuPheGly 515 (2) INFORMATION FOR SEQ ID NO:42: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 26 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: DNA (genomic) (vi) ORIGINAL SOURCE: (C) INDIVIDUAL ISOLATE: Oligonucleotide "H" (xi) SEQUENCE DESCRIPTION: SEQ ID NO:42: CGAATAAACAAGCTAATATACCCGAG26 (2) INFORMATION FOR SEQ ID NO:43: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 26 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: DNA (genomic) (vi) ORIGINAL SOURCE: (C) INDIVIDUAL ISOLATE: Oligonucleotide "C" (xi) SEQUENCE DESCRIPTION: SEQ ID NO:43: CCTGAAACAGGAATCCCGTCACGCAG26 (2) INFORMATION FOR SEQ ID NO:44: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 20 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: DNA (genomic) (vi) ORIGINAL SOURCE: (C) INDIVIDUAL ISOLATE: Oligonucleotide "S" (xi) SEQUENCE DESCRIPTION: SEQ ID NO:44: GCACCGAGCCGACCGAGTGG20 (2) INFORMATION FOR SEQ ID NO:45: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 26 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: DNA (genomic) (vi) ORIGINAL SOURCE: (C) INDIVIDUAL ISOLATE: Primer GF (xi) SEQUENCE DESCRIPTION: SEQ ID NO:45: CGCGAGATCTCATGGGTTTACCCGTG26 (2) INFORMATION FOR SEQ ID NO:46: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 30 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: DNA (genomic) (vi) ORIGINAL SOURCE: (C) INDIVIDUAL ISOLATE: Primer GR (xi) SEQUENCE DESCRIPTION: SEQ ID NO:46: GCGCGAATTCTAGAGACGTAACCCTCCGCC30 (2) INFORMATION FOR SEQ ID NO:47: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 17 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: DNA (genomic) (vi) ORIGINAL SOURCE: (C) INDIVIDUAL ISOLATE: Primer 42F (xi) SEQUENCE DESCRIPTION: SEQ ID NO:47: CTGCTGTTAGGCATTGG17 (2) INFORMATION FOR SEQ ID NO:48: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 26 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: DNA (genomic) (vi) ORIGINAL SOURCE: (C) INDIVIDUAL ISOLATE: Primer 42R (xi) SEQUENCE DESCRIPTION: SEQ ID NO:48: CGCGAATTCAGGCCTGGTCTCCATGC26 (2) INFORMATION FOR SEQ ID NO:49: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 24 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: DNA (genomic) (vi) ORIGINAL SOURCE: (C) INDIVIDUAL ISOLATE: Primer 4F (xi) SEQUENCE DESCRIPTION: SEQ ID NO:49: GCGCAGATCTCCGCTGCGACGCTG24 (2) INFORMATION FOR SEQ ID NO:50: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 25 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: DNA (genomic) (vi) ORIGINAL SOURCE: (C) INDIVIDUAL ISOLATE: Primer 4R (xi) SEQUENCE DESCRIPTION: SEQ ID NO:50: GCGCGAATTCTTAGCCTGAGCCAAG25 (2) INFORMATION FOR SEQ ID NO:51: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 1967 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: double (D) TOPOLOGY: linear (ii) MOLECULE TYPE: DNA (genomic) (vi) ORIGINAL SOURCE: (C) INDIVIDUAL ISOLATE: Heterologous HGV DNA in Vector G (xi) SEQUENCE DESCRIPTION: SEQ ID NO:51: TCATGGGTTTACCCGTGGTTGCGCGCCGTGGTGATGAGGTTCTCATCGGCGTCTTCCAGG60 ATGTGAATCATTTGCCTCCCGGGTTTGTTCCGACCGCGCCTGTTGTCATCCGACGGTGCG120 GAAAGGGCTTCTTGGGGGTCACAAAGGCTGCCTTGACAGGTCGGGATCCTGACTTACATC180 CAGGGAACGTCATGGTGTTGGGGACGGCTACGTCGCGAAGCATGGGAACATGCTTGAACG240 GCCTGCTGTTCACGACCTTCCATGGGGCTTCATCCCGAACCATCGCCACACCCGTGGGGG300 CCCTTAATCCCAGATGGTGGTCAGCCAGTGATGATGTCACGGTGTATCCACTCCCGGATG360 GGGCTACTTCGTTAACACCTTGTACTTGCCAGGCTGAGTCCTGTTGGGTCATCAGATCCG420 ACGGGGCCCTATGCCATGGCTTGAGCAAGGGGGACAAGGTGGAGCTGGATGTGGCCATGG480 AGGTCTCTGACTTCCGTGGCTCGTCTGGCTCACCGGTCCTATGTGACGAAGGGCACGCAG540 TAGGAATGCTCGTGTCTGTGCTTCACTCCGGTGGTAGGGTCACCGCGGCACGGTTCACTA600 GGCCGTGGACCCAAGTGCCAACAGATGCCAAAACCACTACTGAACCCCCTCCGGTGCCGG660 CCAAAGGAGTTTTCAAAGAGGCCCCGTTGTTTATGCCTACGGGAGCGGGAAAGAGCACTC720 GCGTCCCGTTGGAGTACGATAACATGGGGCACAAGGTCTTAATCTTGAACCCCTCAGTGG780 CCACTGTGCGGGCCATGGGCCCGTACATGGAGCGGCTGGCGGGTAAACATCCAAGTATAT840 ACTGTGGGCATGATACAACTGCTTTCACAAGGATCACTGACTCCCCCCTGACGTATTCAA900 CCTATGGGAGGTTTTTGGCCAACCCTAGGCAGATGCTACGGGGCGTTTCGGTGGTCATTT960 GTGATGAGTGCCACAGTCATGACTCAACCGTGCTGTTAGGCATTGGGAGAGTCCGGGAGC1020 TGGCGCGTGGGTGCGGGGTGCAACTAGTGCTCTACGCCACCGCTACACCTCCCGGATCCC1080 CTATGACGCAGCACCCTTCCATAATTGAGACAAAATTGGACGTGGGCGAGATTCCCTTTT1140 ATGGGCATGGAATACCCCTCGAGCGGATGCGAACCGGAAGGCACCTCGTGTTCTGCCATT1200 CTAAGGCTGAGTGCGAGCGCCTTGCTGGCCAGTTCTCCGCTAGGGGGGTCAATGCCATTG1260 CCTATTATAGGGGTAAAGACAGTTCTATCATCAAGGATGGGGACCTGGTGGTCTGTGCTA1320 CAGACGCGCTTTCCACTGGGTACACTGGAAATTTCGACTCCGTCACCGACTGTGGATTAG1380 TGGTGGAGGAGGTCGTTGAGGTGACCCTTGATCCCACCATTACCATCTCCCTGCGGACAG1440 TGCCTGCGTCGGCTGAACTGTCGATGCAAAGACGAGGACGCACGGGTAGGGGCAGGTCTG1500 GACGCTACTACTACGCGGGGGTGGGCAAAGCCCCTGCGGGTGTGGTGCGCTCAGGTCCTG1560 TCTGGTCGGCGGTGGAAGCTGGAGTGACCTGGTACGGAATGGAACCTGACTTGACAGCTA1620 ACCTACTGAGACTTTACGACGACTGCCCTTACACCGCAGCCGTCGCGGCTGATATCGGAG1680 AAGCCGCGGTGTTCTTCTCTGGGCTCGCCCCATTGAGGATGCACCCTGATGTCAGCTGGG1740 CAAAAGTTCGCGGCGTCAACTGGCCCCTCTTGGTGGGTGTTCAGCGGACCATGTGTCGGG1800 AAACACTGTCTCCCGGCCCATCGGATGACCCCCAATGGGCAGGTCTGAAGGGCCCAAATC1860 CTGTCCCACTCCTGCTGAGGTGGGGCAATGATTTACCATCTAAAGTGGCCGGCCACCACA1920 TAGTGGACGACCTGGTCCGGAGACTCGGTGTGGCGGAGGGTTACGTC1967 (2) INFORMATION FOR SEQ ID NO:52: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 2379 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: double (D) TOPOLOGY: linear (ii) MOLECULE TYPE: DNA (genomic) (vi) ORIGINAL SOURCE: (C) INDIVIDUAL ISOLATE: Heterologous HGV DNA in Vector 42 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:52: ATCTTGGTGTCCCGGCCCTCGTTGCGGCGTTTGGCTCGGGTGGTTGAGTGCTGTGTGATG60 GCGGGTGAGAAGGCCACAACCGTCCGGCTGGTCTCCAAGATGTGTGCGAGAGGAGCTTAT120 TTGTTCGATCATATGGGCTCTTTTTCGCGTGCTGTCAAGGAGCGCCTGTTGGAATGGGAC180 GCAGCTCTTGAACCTCTGTCATTCACTAGGACGGACTGTCGCATCATACGGGATGCCGCG240 AGGACTTTGTCCTGCGGGCAGTGCGTCATGGGTTTACCCGTGGTTGCGCGCCGTGGTGAT300 GAGGTTCTCATCGGCGTCTTCCAGGATGTGAATCATTTGCCTCCCGGGTTTGTTCCGACC360 GCGCCTGTTGTCATCCGACGGTGCGGAAAGGGCTTCTTGGGGGTCACAAAGGCTGCCTTG420 ACAGGTCGGGATCCTGACTTACATCCAGGGAACGTCATGGTGTTGGGGACGGCTACGTCG480 CGAAGCATGGGAACATGCTTGAACGGCCTGCTGTTCACGACCTTCCATGGGGCTTCATCC540 CGAACCATCGCCACACCCGTGGGGGCCCTTAATCCCAGATGGTGGTCAGCCAGTGATGAT600 GTCACGGTGTATCCACTCCCGGATGGGGCTACTTCGTTAACACCTTGTACTTGCCAGGCT660 GAGTCCTGTTGGGTCATCAGATCCGACGGGGCCCTATGCCATGGCTTGAGCAAGGGGGAC720 AAGGTGGAGCTGGATGTGGCCATGGAGGTCTCTGACTTCCGTGGCTCGTCTGGCTCACCG780 GTCCTATGTGACGAAGGGCACGCAGTAGGAATGCTCGTGTCTGTGCTTCACTCCGGTGGT840 AGGGTCACCGCGGCACGGTTCACTAGGCCGTGGACCCAAGTGCCAACAGATGCCAAAACC900 ACTACTGAACCCCCTCCGGTGCCGGCCAAAGGAGTTTTCAAAGAGGCCCCGTTGTTTATG960 CCTACGGGAGCGGGAAAGAGCACTCGCGTCCCGTTGGAGTACGATAACATGGGGCACAAG1020 GTCTTAATCTTGAACCCCTCAGTGGCCACTGTGCGGGCCATGGGCCCGTACATGGAGCGG1080 CTGGCGGGTAAACATCCAAGTATATACTGTGGGCATGATACAACTGCTTTCACAAGGATC1140 ACTGACTCCCCCCTGACGTATTCAACCTATGGGAGGTTTTTGGCCAACCCTAGGCAGATG1200 CTACGGGGCGTTTCGGTGGTCATTTGTGATGAGTGCCACAGTCATGACTCAACCGTGCTG1260 TTAGGCATTGGGAGAGTCCGGGAGCTGGCGCGTGGGTGCGGGGTGCAACTAGTGCTCTAC1320 GCCACCGCTACACCTCCCGGATCCCCTATGACGCAGCACCCTTCCATAATTGAGACAAAA1380 TTGGACGTGGGCGAGATTCCCTTTTATGGGCATGGAATACCCCTCGAGCGGATGCGAACC1440 GGAAGGCACCTCGTGTTCTGCCATTCTAAGGCTGAGTGCGAGCGCCTTGCTGGCCAGTTC1500 TCCGCTAGGGGGGTCAATGCCATTGCCTATTATAGGGGTAAAGACAGTTCTATCATCAAG1560 GATGGGGACCTGGTGGTCTGTGCTACAGACGCGCTTTCCACTGGGTACACTGGAAATTTC1620 GACTCCGTCACCGACTGTGGATTAGTGGTGGAGGAGGTCGTTGAGGTGACCCTTGATCCC1680 ACCATTACCATCTCCCTGCGGACAGTGCCTGCGTCGGCTGAACTGTCGATGCAAAGACGA1740 GGACGCACGGGTAGGGGCAGGTCTGGACGCTACTACTACGCGGGGGTGGGCAAAGCCCCT1800 GCGGGTGTGGTGCGCTCAGGTCCTGTCTGGTCGGCGGTGGAAGCTGGAGTGACCTGGTAC1860 GGAATGGAACCTGACTTGACAGCTAACCTACTGAGACTTTACGACGACTGCCCTTACACC1920 GCAGCCGTCGCGGCTGATATCGGAGAAGCCGCGGTGTTCTTCTCTGGGCTCGCCCCATTG1980 AGGATGCACCCTGATGTCAGCTGGGCAAAAGTTCGCGGCGTCAACTGGCCCCTCTTGGTG2040 GGTGTTCAGCGGACCATGTGTCGGGAAACACTGTCTCCCGGCCCATCGGATGACCCCCAA2100 TGGGCAGGTCTGAAGGGCCCAAATCCTGTCCCACTCCTGCTGAGGTGGGGCAATGATTTA2160 CCATCTAAAGTGGCCGGCCACCACATAGTGGACGACCTGGTCCGGAGACTCGGTGTGGCG2220 GAGGGTTACGTCCGCTGCGACGCTGGGCCGATCTTGATGATCGGTCTAGCTATCGCGGGG2280 GGAATGATCTACGCGTCATACACCGGGTCGCTAGTGGTGGTGACAGACTGGGATGTGAAG2340 GGGGGTGGCGCCCCCCTTTATCGGCATGGAGACCAGGCC2379 (2) INFORMATION FOR SEQ ID NO:53: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 2232 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: double (D) TOPOLOGY: linear (ii) MOLECULE TYPE: DNA (genomic) (vi) ORIGINAL SOURCE: (C) INDIVIDUAL ISOLATE: Heterologous HGV DNA in Vector 23 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:53: ATCTTGGTGTCCCGGCCCTCGTTGCGGCGTTTGGCTCGGGTGGTTGAGTGCTGTGTGATG60 GCGGGTGAGAAGGCCACAACCGTCCGGCTGGTCTCCAAGATGTGTGCGAGAGGAGCTTAT120 TTGTTCGATCATATGGGCTCTTTTTCGCGTGCTGTCAAGGAGCGCCTGTTGGAATGGGAC180 GCAGCTCTTGAACCTCTGTCATTCACTAGGACGGACTGTCGCATCATACGGGATGCCGCG240 AGGACTTTGTCCTGCGGGCAGTGCGTCATGGGTTTACCCGTGGTTGCGCGCCGTGGTGAT300 GAGGTTCTCATCGGCGTCTTCCAGGATGTGAATCATTTGCCTCCCGGGTTTGTTCCGACC360 GCGCCTGTTGTCATCCGACGGTGCGGAAAGGGCTTCTTGGGGGTCACAAAGGCTGCCTTG420 ACAGGTCGGGATCCTGACTTACATCCAGGGAACGTCATGGTGTTGGGGACGGCTACGTCG480 CGAAGCATGGGAACATGCTTGAACGGCCTGCTGTTCACGACCTTCCATGGGGCTTCATCC540 CGAACCATCGCCACACCCGTGGGGGCCCTTAATCCCAGATGGTGGTCAGCCAGTGATGAT600 GTCACGGTGTATCCACTCCCGGATGGGGCTACTTCGTTAACACCTTGTACTTGCCAGGCT660 GAGTCCTGTTGGGTCATCAGATCCGACGGGGCCCTATGCCATGGCTTGAGCAAGGGGGAC720 AAGGTGGAGCTGGATGTGGCCATGGAGGTCTCTGACTTCCGTGGCTCGTCTGGCTCACCG780 GTCCTATGTGACGAAGGGCACGCAGTAGGAATGCTCGTGTCTGTGCTTCACTCCGGTGGT840 AGGGTCACCGCGGCACGGTTCACTAGGCCGTGGACCCAAGTGCCAACAGATGCCAAAACC900 ACTACTGAACCCCCTCCGGTGCCGGCCAAAGGAGTTTTCAAAGAGGCCCCGTTGTTTATG960 CCTACGGGAGCGGGAAAGAGCACTCGCGTCCCGTTGGAGTACGATAACATGGGGCACAAG1020 GTCTTAATCTTGAACCCCTCAGTGGCCACTGTGCGGGCCATGGGCCCGTACATGGAGCGG1080 CTGGCGGGTAAACATCCAAGTATATACTGTGGGCATGATACAACTGCTTTCACAAGGATC1140 ACTGACTCCCCCCTGACGTATTCAACCTATGGGAGGTTTTTGGCCAACCCTAGGCAGATG1200 CTACGGGGCGTTTCGGTGGTCATTTGTGATGAGTGCCACAGTCATGACTCAACCGTGCTG1260 TTAGGCATTGGGAGAGTCCGGGAGCTGGCGCGTGGGTGCGGGGTGCAACTAGTGCTCTAC1320 GCCACCGCTACACCTCCCGGATCCCCTATGACGCAGCACCCTTCCATAATTGAGACAAAA1380 TTGGACGTGGGCGAGATTCCCTTTTATGGGCATGGAATACCCCTCGAGCGGATGCGAACC1440 GGAAGGCACCTCGTGTTCTGCCATTCTAAGGCTGAGTGCGAGCGCCTTGCTGGCCAGTTC1500 TCCGCTAGGGGGGTCAATGCCATTGCCTATTATAGGGGTAAAGACAGTTCTATCATCAAG1560 GATGGGGACCTGGTGGTCTGTGCTACAGACGCGCTTTCCACTGGGTACACTGGAAATTTC1620 GACTCCGTCACCGACTGTGGATTAGTGGTGGAGGAGGTCGTTGAGGTGACCCTTGATCCC1680 ACCATTACCATCTCCCTGCGGACAGTGCCTGCGTCGGCTGAACTGTCGATGCAAAGACGA1740 GGACGCACGGGTAGGGGCAGGTCTGGACGCTACTACTACGCGGGGGTGGGCAAAGCCCCT1800 GCGGGTGTGGTGCGCTCAGGTCCTGTCTGGTCGGCGGTGGAAGCTGGAGTGACCTGGTAC1860 GGAATGGAACCTGACTTGACAGCTAACCTACTGAGACTTTACGACGACTGCCCTTACACC1920 GCAGCCGTCGCGGCTGATATCGGAGAAGCCGCGGTGTTCTTCTCTGGGCTCGCCCCATTG1980 AGGATGCACCCTGATGTCAGCTGGGCAAAAGTTCGCGGCGTCAACTGGCCCCTCTTGGTG2040 GGTGTTCAGCGGACCATGTGTCGGGAAACACTGTCTCCCGGCCCATCGGATGACCCCCAA2100 TGGGCAGGTCTGAAGGGCCCAAATCCTGTCCCACTCCTGCTGAGGTGGGGCAATGATTTA2160 CCATCTAAAGTGGCCGGCCACCACATAGTGGACGACCTGGTCCGGAGACTCGGTGTGGCG2220 GAGGGTTACGTC2232 (2) INFORMATION FOR SEQ ID NO:54: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 573 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: double (D) TOPOLOGY: linear (ii) MOLECULE TYPE: DNA (genomic) (vi) ORIGINAL SOURCE: (C) INDIVIDUAL ISOLATE: Heterologous HGV DNA in Vector 4 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:54: GCGCCTGTTGTCATCCGACGGTGCGGAAAGGGCTTCTTGGGGGTCACAAAGGCTGCCTTG60 ACAGGTCGGGATCCTGACTTACATCCAGGGAACGTCATGGTGTTGGGGACGGCTACGTCG120 CGAAGCATGGGAACATGCTTGAACGGCCTGCTGTTCACGACCTTCCATGGGGCTTCATCC180 CGAACCATCGCCACACCCGTGGGGGCCCTTAATCCCAGATGGTGGTCAGCCAGTGATGAT240 GTCACGGTGTATCCACTCCCGGATGGGGCTACTTCGTTAACACCTTGTACTTGCCAGGCT300 GAGTCCTGTTGGGTCATCAGATCCGACGGGGCCCTATGCCATGGCTTGAGCAAGGGGGAC360 AAGGTGGAGCTGGATGTGGCCATGGAGGTCTCTGACTTCCGTGGCTCGTCTGGCTCACCG420 GTCCTATGTGACGAAGGGCACGCAGTAGGAATGCTCGTGTCTGTGCTTCACTCCGGTGGT480 AGGGTCACCGCGGCACGGTTCACTAGGCCGTGGACCCAAGTGCCAACAGATGCCAAAACC540 ACTACTGAACCCCCTCCGGTGCCGGCCAAAGGA573 (2) INFORMATION FOR SEQ ID NO:55: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 1290 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: double (D) TOPOLOGY: linear (ii) MOLECULE TYPE: DNA (genomic) (vi) ORIGINAL SOURCE: (C) INDIVIDUAL ISOLATE: Heterologous HGV DNA in Vector Q (xi) SEQUENCE DESCRIPTION: SEQ ID NO:55: GATCTGTGGTATGCCATCCCGGTACTGACCAGCCCGGGGGCGGGCCTTGCGGGGATCGCT60 CTCGGGTTGGTTTTGTATTCAGCTAACAACTCTGGCACTACCACTTGGTTGAACCGTCTG120 CTGACTACGTTACCAAGGTCTTCATGTATCCCGGACAGTTACTTTCAGCAAGTTGACTAT180 TGCGACAAGGTCTCAGCCGTGCTCCGGCGCCTGAGCCTCACCCGCACAGTGGTTGCCCTG240 GTCAACAGGGAGCCTAAGGTGGATGAGGTACAGGTGGGGTATGTCTGGGACCTGTGGGAG300 TGGATCATGCGCCAAGTGCGCGTGGTCATGGCCAGACTCAGGGCCCTCTGCCCCGTGGTG360 TCACTACCCTTGTGGCATTGCGGGGAGGGGTGGTCCGGGGAATGGTTGCTTGACGGTCAT420 GTTGAGAGTCGCTGCCTCTGTGGCTGCGTGATCACTGGTGACGTTCTGAATGGGCAACTC480 AAAGAACCAGTTTACTCTACCAAGCTGTGCCGGCACTATTGGATGGGGACTGTCCCTGTG540 AACATGCTGGGTTACGGTGAAACGTCGCCTCTCCTGGCCTCCGACACCCCGAAGGTTGTG600 CCCTTCGGGACGTCTGGCTGGGCTGAGGTGGTGGTGACCACTACCCACGTGGTAATCAGG660 AGGACCTCCGCCTATAAGCTGCTGCGCCAGCAAATCCTATCGGCTGCTGTAGCTGAGCCC720 TACTACGTCGACGGCATTCCGGTCTCATGGGACGCGGACGCTCGTGCGCCCGCCATGGTC780 TATGGCCCTGGGCAAAGTGTTACCATTGACGGGGAGCGCTACACCTTGCCTCATCAACTG840 AGGCTCAGGAATGTGGCACCCTCTGAGGTTTCATCCGAGGTGTCCATTGACATTGGGACG900 GAGACTGAAGACTCAGAACTGACTGAGGCCGATCTGCCGCCGGCGGCTGCTGCTCTCCAA960 GCGATCGAGAATGCTGCGAGGATTCTTGAACCGCACATTGATGTCATCATGGAGGACTGC1020 AGTACACCCTCTCTTTGTGGTAGTAGCCGAGAGATGCCTGTATGGGGAGAAGACATCCCC1080 CGTACTCCATCGCCAGCACTTATCTCGGTTACTGAGAGCAGCTCAGATGAGAAGACCCCG1140 TCGGTGTCCTCCTCGCAGGAGGATACCCCGTCCTCTGACTCATTCGAGGTCATCCAAGAG1200 TCCGAGACAGCCGAAGGGGAGGAAAGTGTCTTCAACGTGGCTCTTTCCGTATTAAAAGCC1260 TTATTTCCACAGAGCGACGCGACCAGGAAG1290 (2) INFORMATION FOR SEQ ID NO:56: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 2388 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: double (D) TOPOLOGY: linear (ii) MOLECULE TYPE: DNA (genomic) (vi) ORIGINAL SOURCE: (C) INDIVIDUAL ISOLATE: Heterologous HGV DNA in Vector N (xi) SEQUENCE DESCRIPTION: SEQ ID NO:56: CGCTACACCTTGCCTCATCAACTGAGGCTCAGGAATGTGGCACCCTCTGAGGTTTCATCC60 GAGGTGTCCATTGACATTGGGACGGAGACTGAAGACTCAGAACTGACTGAGGCCGATCTG120 CCGCCGGCGGCTGCTGCTCTCCAAGCGATCGAGAATGCTGCGAGGATTCTTGAACCGCAC180 ATTGATGTCATCATGGAGGACTGCAGTACACCCTCTCTTTGTGGTAGTAGCCGAGAGATG240 CCTGTATGGGGAGAAGACATCCCCCGTACTCCATCGCCAGCACTTATCTCGGTTACTGAG300 AGCAGCTCAGATGAGAAGACCCCGTCGGTGTCCTCCTCGCAGGAGGATACCCCGTCCTCT360 GACTCATTCGAGGTCATCCAAGAGTCCGAGACAGCCGAAGGGGAGGAAAGTGTCTTCAAC420 GTGGCTCTTTCCGTATTAAAAGCCTTATTTCCACAGAGCGACGCGACCAGGAAGCTTACC480 GTCAAGATGTCGTGCTGCGTTGAAAAGAGCGTCACGCGCTTTTTCTCATTGGGGTTGACG540 GTGGCTGATGTTGCTAGCCTGTGTGAGATGGAAATCCAGAACCATACAGCCTATTGTGAC600 CAGGTGCGCACTCCGCTTGAATTGCAGGTTGGGTGCTTGGTGGGCAATGAACTTACCTTT660 GAATGTGACAAGTGTGAGGCTAGGCAAGAAACCTTGGCCTCCTTCTCTTACATTTGGTCT720 GGAGTGCCGCTGACTAGGGCCACGCCGGCCAAGCCTCCCGTGGTGAGGCCGGTTGGCTCT780 TTGTTAGTGGCCGACACTACTAAGGTGTATGTTACCAATCCAGACAATGTGGGACGGAGG840 GTGGACAAGGTGACCTTCTGGCGTGCTCCTAGGGTTCATGATAAGTACCTCGTGGACTCT900 ATTGAGCGCGCTAAGAGGGCCGCTCAAGCCTGCCTAAGCATGGGTTACACTTATGAGGAA960 GCAATAAGGACTGTAAGGCCACATGCTGCCATGGGCTGGGGATCTAAGGTGTCGGTTAAG1020 GACTTAGCCACCCCCGCGGGGAAGATGGCCGTCCATGACCGGCTTCAGGAGATACTTGAA1080 GGGACTCCGGTCCCCTTTACTCTTACTGTGAAAAAGGAGGTGTTCTTCAAAGACCGGAAG1140 GAGGAGAAGGCCCCCCGCCTCATTGTGTTCCCCCCCCTGGACTTCCGGATAGCTGAAAAG1200 CTCATCTTGGGAGACCCAGGCCGGGTAGCCAAGGCGGTGTTGGGGGGGGCCTACGCCTTC1260 CAGTACACCCCAAATCAGCGAGTTAAGGAGATGCTCAAGCTATGGGAGTCTAAGAAGACC1320 CCTTGCGCCATCTGTGTGGACGCCACCTGCTTCGACAGTAGCATAACTGAAGAGGACGTG1380 GCTTTGGAGACAGAGCTATACGCTCTGGCCTCTGACCATCCAGAATGGGTGCGGGCACTT1440 GGGAAATACTATGCCTCAGGCACCATGGTCACCCCGGAAGGGGTGCCCGTCGGTGAGAGG1500 TATTGCAGATCCTCGGGTGTCCTAACAACTAGCGCGAGCAACTGCTTGACCTGCTACATC1560 AAGGTGAAAGCTGCCTGTGAGAGAGTGGGGCTGAAAAATGTCTCTCTTCTCATAGCCGGC1620 GATGACTGCTTGATCATATGTGAGCGGCCAGTGTGCGACCCAAGCGACGCTTTGGGCAGA1680 GCCCTAGCGAGCTATGGGTACGCGTGCGAGCCCTCATATCATGCATCATTGGACACGGCC1740 CCCTTCTGCTCCACTTGGCTTGCTGAGTGCAATGCAGATGGGAAGCGCCATTTCTTCCTG1800 ACCACGGACTTCCGGAGGCCGCTCGCTCGCATGTCGAGTGAGTATAGTGACCCGATGGCT1860 TCGGCGATCGGTTACATCCTCCTTTATCCTTGGCACCCCATCACACGGTGGGTCATCATC1920 CCTCATGTGCTAACGTGCGCATTCAGGGGTGGAGGCACACCGTCTGATCCGGTTTGGTGC1980 CAGGTGCATGGTAACTACTACAAGTTTCCACTGGACAAACTGCCTAACATCATCGTGGCC2040 CTCCACGGACCAGCAGCGTTGAGGGTTACCGCAGACACAACTAAAACAAAGATGGAGGCT2100 GGTAAGGTTCTGAGCGACCTCAAGCTCCCTGGCTTAGCAGTCCACCGAAAGAAGGCCGGG2160 GCGTTGCGAACACGCATGCTCCGCTCGCGCGGTTGGGCTGAGTTGGCTAGGGGCTTGTTG2220 TGGCATCCAGGCCTACGGCTTCCTCCCCCTGAGATTGCTGGTATCCCGGGGGGTTTCCCT2280 CTCTCCCCCCCCTATATGGGGGTGGTACATCAATTGGATTTCACAAGCCAGAGGAGTCGC2340 TGGCGGTGGTTGGGGTTCTTAGCCCTGCTCATCGTAGCCCTCTTCGGG2388 __________________________________________________________________________

## Claims

1. A composition, comprising

2. The composition of claim 1, wherein said protease is an NS2B protease encoded by a polynucleotide whose sequence is contained within SEQ ID NO:3.

3. The composition of claim 1, wherein said protease is an NS3 protease encoded by a polynucleotide whose sequence is contained within SEQ ID NO:4.

4. The composition of claim 1, wherein said Hepatitis G virus protease comprises a co-factor encoded by a polynucleotide whose sequence is contained within SEQ ID NO:5.

5. A fusion protein comprising a fusion partner fused to a Hepatitis G virus protease.

6. The fusion protein of claim 5, wherein said fusion partner comprises glutathione-S-transferase.

7. The fusion protein of claim 5, wherein said protease is encoded by a polynucleotide whose sequence is contained within SEQ ID NO:24.

8. The composition of claim 1, wherein said HGV protease comprises a polypeptide encoded by a polynucleotide whose sequence is contained within SEQ ID NO:32.

9. The composition of claim 1, wherein said HGV protease comprises a polypeptide encoded by a polynucleotide whose sequence is contained within SEQ ID NO:34.

10. The composition of claim 1, wherein said HGV protease comprises a polypeptide encoded by a polynucleotide whose sequence is contained within SEQ ID NO:36.