MAREK'S DISEASE HERPESVIRUS DNA SEGMENT ENCODING GLYCOPROTEINS, gD, gI AND gE

Abstract: DNA encoding glycoproteins gD, gI and gE from Marek's disease herpesvirus is described. The DNA is useful for probes to detect the DNA in the herpesvirus, for expression to produce the glycoproteins that can be used for producing the antibodies which specifically recognize the three glycoprotein antigens, and in the case of the latter two genes, for potential insertion sites for foreign genes and as possible sites for gene inactivation to attenuate MDV field isolates for vaccine purposes.

Description: MAREK'S DISEASE HERPESVIRUS DNA SEGMENT ENCODING GLYCOPROTEINS, gD, gl and gE Cross-Reference to Related Application This application is a continuation-in-part of U.S. application Serial No. 07/572,711, filed August 24, 1990. BACKGROUND OF THE INVE" " "ION (1) Field of the lnvei--ion The present invention relates to segments of the Mare 's Disease Herpesvirus genome, from its unique short (Ug) region encoding glycoproteins gD, gl and gE, and to novel glycoproteins produced therefrom. In particular, the present i * sntion relates „o DNA segments containing genes encoding tnese glycoprotein antigens and containing potential promoter sequences up to 400 nucleotides 5' of each gene, segments which are useful for probing for Marek's disease herpesvirus, as a possible source for Marek's disease virus (MDV) promoters, for gene expression to produce the glycoproteins that in turn can be used for producing antibodies which recognize the three glycoprotein antigens, and in the case of the latter two genes, for potential insertion sites for foreign genes and as possible sites for gene inactivation to attenuate MDV field isolates for vaccine purposes. (2) Prior Art MDV is an oncogenic herpesvirus of chickens, which is known to cause T cell lymphomas and peripheral nerve demyelination. The resulting disease, Marek's disease (MD), was the first naturally occurring lymphomatous disorder to be effectively controlled via vaccination, using either the antigenically related, yet apathogenic, herpesvirus of turkeys (HVT) or atter. ated field isolates of MDV. Because of similar biological properties, especially its ly photropism, MDV has been classified as a member of the gammaherpesvirus subfamily (Roizman, B., et al., Intervirology 16:201-217 (1981)). Of the three herpesvirus subfamilies, gammaherpesviruses exhibit particularly marked differences with regard to genome composition and organization. For example, the B-lymphotropic Epstein-Barr virus (EBV) of humans has a " 172.3 kbp genome with 60% G+C content, is bounded by terminal 0.5 kbp direct repeats and contains a characteristic set of internal 3.07 kbp tandem repeats (Baer, R., et al. , Nature (London) 310:207-211 (1984)). Herpesvirus saimiri (HVS), a T-lymphotropic herpesvirus of new-world monkeys and lower vertebrates, has an A+τ rich coding sequence (112 kbp; 36% G+C; i.e. L-DNA) without any large-scale internal redundancy, but contains instead greater than 30 reiterations of a 1.44 kbp sequence of 71% G+C at the termini of the genome (H-DNA) (Banker, A. T. , et al., J. Virol. 55:133-139 (1985)). Despite the structural differences between EBV and HVS, the genomes of these two viruses encode serologically related proteins and share a common organization of coding sequences which differs from that of the neurotropic alphaherpesviruses, exemplified by herpes simplex virus (HSV) and varicella-zoster virus (VZV) (Ca erion, K. R. , et al., J. Virol. 61:2063-2070 (1987); Davison, A. J. , et al., J. Gen. Virol. 68:1067-1079 (1987); Davison, A. J. , et al., J. Gen. Virol. 67:597-611 (1986); Davison, A. J. , et al., J. Gen. Virol. 76:1759-1816 (1986); Davison, A. J. , et al., J. Gen. Virol. 64:1927-1942 (1983); Gompels, ϋ. A., J. of Virol. 62:757-767 (1988); and Nichols, J., et al., J. of Virol. 62:3250-3257 (1988)). In contrast to other gammaherpesviruses, MDV has a genome structure closely resembling that of the alphaherpesviruses (Cebrian, J., et al., Proc. Natl. Acad. Sci. USA 79:555-558 (1982); and Fukuchi, K., et al., J. Virol. 51:102-109 (1984)) . Members of the latter subfamily have similar genome structures consisting of covalently joined long (L)'and short (S) segments. Each segment comprises a unique (U) segment (UL, Ug) flanked by a pair (terminal and internals) of inverted repeat regions (TRL, IRj.; TRg; respectively). Alphaherpesviruses include human HSV and VZV, porcine pseudorabies virus (PRV) , bovine herpesvirus (BHV) and equine herpesvirus (EHV) . Because MDV contains extensive repeat sequences flanking its U . region, its genome structure most resembles that of HSV- (Cebrian, J., et al., Proc. Natl. Acad. Sci. USA 79:555-558 (1982); and Fukuchi , K., et al., J. Virol. 51:102-109 (1984)). Recent studies (Buckmaster, A. E. , et al., J. Gen. Virol. 69:2033-2042 (1988)) have shown that the two gammaherpesviruses, MDV and HVT, appear to bear greater similarity to the alphaherpesviruses, VZV and HSV, than to the gammaherpesvirus, EBV. This was based on a comparison of numerous randomly isolated MDV and HVT clones at the predicted amino acid level; not only did individual sequences exhibit greater relatedness to alphaherpesvirus genes than to gammaherpesvirus genes, but the two viral genomes were found to be generally collinear with VZV, at least with respect to the unique long (UL) region. Such collinearity of U genes extends to other alphaherpesviruses such as HSV-1, HSV-2, EHV-1 and PRV as evidenced by both sequence analysis (McGeoch, D. J., et al., J. Gen. Virol. 69:1531-1574 (1988)) and DNA hybridization experiments (Davison, A. J., et al., J. Gen. Virol. 64:1927-1942 (1983)). Many of these U L genes are shared by other herpesviruses, including the beta- and gammaherpesviruses (Davison, A. J. , et al., J. Gen. Virol. 68:1067-1079 (1987)). The organization and comparison of such genes has suggested the past occurrence of large-scale rearrangements to account for the divergence of herpesviruses from a common ancestor. Unfortunately, such a hypothesis fails to account for the presence of alphaherpesvirus S component (unique short, Ug, and associated inverted/terminal repeat short, IRg, TRg) genes which appear unique to members of this subfamily (Davison, A. J., et al., J. Gen. Virol. 68:1067-1079 (1987); Davison, A. J. , et al., J. Gen. Virol. 67:597-611 (1986); and McGeoch, D. J., et al., J. Mol. Biol. 181:1-13 (1985)). The DNA sequence and organization of genes in a 5.5 kbp EcoRl fragment mapping in the Ug region of MDV strain RBIB was described by Ross , Binns and Pastorek (Ross, L. J. N. , et al. Journal of General Virology. 72:949-954 (1991)). The properties and evolutionary relationships of four of the predicted polypeptides was also described (Ross, L. J. N. and M. M. Binns, Journal of General Virology, 72:939-947 (1991)). In that fragment they found the homologs of HSV US2, US3, US6 (gD) and US7 (gl), as well as an MDV specific gene. For the latter, only part of the gene was present. These reports confirm the presence of four MDV Ug genes, and the evolutionary relationship proposed above. It is important to note that no evidence for US8 (gE), or the genes to the left of US2 were described. In addition to its uniqueness compared with beta- and gammaherpesviruses, the alphaherpesvirus Ug region is particularly interesting because of marked differences in its content and genetic organization within the latter subfamily (e.g. HSV-1 Ug=13.0 kbp, 12 genes, McGeoch, D. J., et al., J. Mol. Biol. 181:1-13 (1985)); VZ Ug=5.2 kbp, 4 genes, Davison, A. J., et al., J. Gen. Virol 76:1759-1816 (1986)). In the case of HSV-1, 11 of the 12 Ug genes have been found to be dispensable for replication in cell culture (Longnecker, R., et al., Proc. Natl. Acad. Sci. USA 84:4303-4307 (1987)). This has suggested the potential involvement of these genes in pathogenesis and/o latency (Longnecker, R., et al., Proc. Natl. Acad. Sci. US 84:4303-4307 (1987); Meignier, B., et al.. Virology 162:251-254 (1988); and Weber, P. C. , et al.. Science 236-576-579 (1987)). In the report by Buckmaster et al. (Buckmaster, A. E. , et al., J. Gen. Virol. 69:2033-2042 (1988)), except for the identification of partial MDV sequences homologous to HSV immediate early protein alpha 22 (USD and the serine-threonine protein kinase (US3) , t content, localizatio and organization of MDV S component homologs was not determined. Moreover, despite the presence of at least four HSV Ug glycoprotein genes (two in VZV), no such homologs were identified. In application Serial No. 07/229,011 filed August 5, 1988, including Leland F. Velicer, one of the present inventors, the Marek's Disease herpesvirus DNA segment possibly containing the gene encoding the glycoprotein B antigen complex (gplOO, gp60, gp49) was identified but not sequenced. Antigen B is an important glycoprotein complex because it can elicit at least partial protective immunity, and thus MDV DNA segment can be used for probes, as a possible source for promoters in the gene's 5' regulatory region, and f or gene expression to produce the glycoproteins, which t turn can be used to produce antibodies that recognize the glycoprotein antigens. However, there was no discussion of the glycoproteins of the present invention. These B antigen glycoproteins are not encoded by the Ug region and thus are from a different region of the MDV genome. In application Serial No. 07/526,790, filed May 17, 1987 by Leland F. Velicer, the MDV herpesvirus DNA segment containing the gene encoding the glycoprotein A antigen (gp5 J -65) is described but not sequenced. This MDV DNA segment is useful as probes, as a possible source for promoters in the gene's 5' regulatory region, and for producing antibodies by the sequence of events described above. This DNA is also important because antigen A is now known to be a homolog of HSV gC, a gene non-essential for replication in cell culture. Since that property most likely also plies to the MDV homolog, it may be useful as a site for iύjertion of foreign genes, however, there was no discussion of the glycoproteins of the present invention, This glycoprotein is also not encoded by the Ug region and is thus from a different region of the MDV genome. Other glycoproteins are encoded by Marek's disease herpesvirus genome. In application Serial No. 07/572,711, filed August 24, 1990 by Leland F. Velicer, et al., the MDV DNA containing the genes encoding the MDV, gD, gl and part of gE glycoproteins is described, with MDV nucleotide sequences for the complete gD and gl genes and part of gE (MDV homologs of HSV genes US6, US7, US8, respectively) . This MDV DNA segment is useful as probes, as a possible source for promoters in the gene's 5' regulatory region, and for producing antibodies by the sequence of events described above. The present invention is particularly directed to the complete gene (US8) encoding glycoprotein gE. OBJECTS It is an object of the present invention to provide sequenced DNA encoding glycoproteins gD, gl and gE, both together and individually. It is further an object of the present invention to provide DNA segments encoding these glycoprotein antigens and containing potential promoter sequences up to 400 nucleotides 5' of each gene; which are useful as DNA probes, as a possible source for MDV promoters, for producing antibodies which recognize the antigens and, in the case of the latter two glycoproteins, as insertion sites for foreign genes and as possible sites for gene inactivation to attenuate MDV field isolates for vaccine purposes. These and other objects will become increasingly apparent by reference to the following description and the drawings. IN THE DRAWINGS Figures 1A to C show map location, sequencing strategy and organization of MDV open reading frames (ORFs): Figure 1A includes MDV genomic structure and restriction maps outlining area sequenced. Figure IB includes map location and sequencing strategy. Boxes define plasmid clones with BamHl, EcoRl o Sail-bound inserts that were used to generate Ml3mpl8 and -19 templates for DNA sequencing. Rightward and leftward arrows define sequences derived from the top and bottom strands, respectively. The restriction enzyme sites are identified as: B = BamHl, E = EcoRl, Nc = Ncol, Ns = Nsil, S = Sail, and P = Pstl. Sequences derived from random libraries (Sau3A, Taql, Rsal), specific cloned restriction fragments, Bal 31-digested libraries or using synthetically-derived oligonucleotides are denoted by a, b-,. c, and d, respectively. Figure 1C includes organization of the MDV Ug ORFs. Numbers refer to homologs based on relation to HSV-1 Ug ORF nomenclature (McGeoch, D. J. , et al., J. Mol. Biol. 181:1-13 (1985)). Boxes represent location of MDV ORFs. Arrows define direction of transcription/translation. Names of ORFs are displayed above boxes. Potential polyadenylation signals on the top and bottom strands are highlighted by AATAAA and AAATAA, respectively. SORFl and S0RF2 are MDV-specific S component ORFs given arbitrary names. Figure 2 shows nucleotide and predicted amino acid sequences. The nucleotide sequence is given as the rightward 5' to 3' strand only (numbered 1 to 10350). Rightward- and leftward- directed predicted amino acid sequences are shown above and below the corresponding nucleotide sequences in single-letter code, respectively. The name of each ORF is given to the left of the first line of the amino acid sequence. Amino acid sequences are numbered from the first M (three letter code) (ATG in the DNA) at the N-terminus to the last amino acid at the C-terminus, which precedes the termination codon (identified by an *) . Potential TATA consensus sites located within 400 nucleotides of the ATG are underlined and defined as sites containing at least six of seven matches to the TATA(AT)A(AT) consensus sequences defined by Corden et al. (Corden, B., et al. , Science 209:1406-1414 (1980)). Underlines longer than seven nucleotides refer to areas containing overlapping TATA consensus sites. Figure 3A shows alignment of S component homologs showing selected regions displaying maximum amino acid conservation. Gaps have been introduced to maximize alignment of identical amino acids as described in Methods. The consensus sequence (cons) indicates residues that are shared by at least all but one of the viruses and are indicated by capital letters. In alignments between more than two sequences, asterisks (*) indicate residues conserved by all of the viruses. Amino acid numbers (with respect to 5"-ATG) of corresponding regions aligned are listed before and after each sequence. Figure 3B shows the dot matrix analyses depicting overall homologies between selected MDV-alphaherpesvirus S segment homolog comparisons. Points were generated where at least 15 amino acids over a sliding window length of 30 were found identical or similar. The resulting diagonals illustrate regions showing greatest conservation. Amino acid numbers (with respect to 5* -ATG) of corresponding sequences are denoted above and to the right of each plot. Figure 4 shows a comparison of overall genome organization of available S component ORFs (Audonnet, J.-C, et al., J. Gen. Virol. 71:2969-2978 (1990); McGeoch, D. J., et al., J. Gen. Virol. 68:19-38 (1987); Tikoo, S. K., et al., J. Virol. 64:5132-5142 (1990); Van Zijl, M. , et al., J. Gen. Virol. 71:1747-1755 (1990); Zhang, G., et al., J. Gen. Virol. 71:2433-2441 (1990); Cullinane, A. A., et al., J. Gen. Virol. 69:1575-1590 (1988); Davison, A. J., et al., J. Gen. Virol. 76:1759-1816 (1986); McGeoch, D. J. , et al., J. Mol. Biol. 181:1-13 (1985); Petrovskis, E. A., et al.. Virology 159:193-195 (1987); Petrovskis, E. A., et al., J. Virol. 60:185-193 (1986); and Petrovskis, E. A., et al., J. Virol. 59:216-223 (1986)). Numbers above each ORF refer to homologs based on relation to HSV-1 Ug ORF nomenclature (McGeoch, D. J. , et al., J. Mol. Biol. 181:1-13 (1985)). Alternative polypeptide designations common to each system are listed below those ORFs where applicable. Upper and lower case solid bars refer to rightward and leftward-directed ORFs, respectively. Arrows refer to identified IRg-Ug and/or Ug-TRg junction sites. Figure 5 shows the sequence of steps necessary to produce a complete segment of Marek's disease herpesvirus DNA encoding glycoprotein gl and the part of gE included in the application filed August 24, 1990. GENERAL DE S CRIPTION The present invention relates to a segment of DNA of Marek's disease herpesvirus genome encoding multiple glycoproteins, and containing potential promoter sequences up to 400 nucleotides 5* of each gene, between a 1 and 10350 nucleotide sequence as shown in Figure 2 (and identified as SEQ ID No:l). Further, the present invention relates to an EcoRl I segment of Marek's disease herpesvirus genome encoding the glycoprotein D precursor, and subsegments of the DNA. Further, still, the present invention relates to a segment of DNA encoding glycoprotein gD precursor between a 5964 and 7172 nucleotide sequence of Marek's disease herpesvirus DNA, and containing potential promoter sequences up to 400 nucleotides 5' of each gene, as shown in Figure 2 (and identified as part of SEQ ID No. :1) and subsegments of the segment of DNA which recognize the DNA. The present invention also relates to a segment of DNA encoding glycoprotein gl precursor between a 7282 and 8346 nucleotide sequence of Marek's disease herpesvirus DNA, and containing potential promoter sequences up to 400 nucleotides 5' of each gene, as shown in Figure 2 (and identified as part of SEQ ID No:l) and subsegments of the segments that recognize the DNA. The present invention also relates to a segment of DNA encoding glycoprotein gE precursor between a 8488 and 9978 nucleotide sequence of Marek's disease herpesvirus DNA, and containing potential promoter sequences up to 400 nucleotides 5' of each gene, as shown in Figure 2 (and (and identified as part of SEQ ID No:l) and subfragments of the DNA that recognize the DNA. Further, the present invention relates to the novel glycoprotein precursors which are produced by expressions of the genes in the segments of DNA. Further the present invention relates to the " potential MDV gene promoters, which are located in the 400 nucleotides 5' of each coding sequence. SPECIFIC DESCRIPTION The present invention shows a sequence analysis of a 10.35 kbp DNA stretch encompassing a majority of the MDV Ug region. Altogether seven MDV Ug homologs, including three glycoprotein genes and two additional MDV-specific open reading frames, were identified. Example 1 Materials and Methods Recombinant Plasmids, M-13 subcloning and DNA sequencing MDV EcoRl-0 and EcoRl-I of the pathogenic GA strain were previously cloned into pBR328 (Gibbs, C. P., et al., Proc. Natl. Acad. Sci. USA 81:3365-3369 (1984)), (Silva, R. F., et al., J. Virol. 54:690-696 (1985)) and made available by R. F. Silva, USDA Avian Disease and Oncology Lab, East Lansing, MI, where these clones are maintained. GA strain BamHI-A and BamHI-Pl were previously cloned into pACYCl84 and pBR322, respectively (Fukuchi, K., et al., J. Virol. 51:102-109 (1984)) and kindly provided by M. Nonoyama, Showa University Research Institute, St. Petersburg, FL. GA strain clone GA-02, an EMBL-3 clone containing a partially digested MDV Sail insert, which contains BamHI-A, -Pi, and additional 5' and 3' flanking sequences (kindly provided by P. Sondermeier, Intervet Intl. B. V., Boxmeer, The Netherlands) was used to extend analysis to the right of the above EcoRl and BamHl fragments. This phage clone was used to generate pUClδ subclones with smaller Sal I-bound inserts (psPl8-A, pSPl8-B, and pSPlδ-C) containing the 3' BamHl-Pl-flanking region. These clones (Figure IB) were used to generate Ml3ir.pl8 and -19 subclones for use as templates for nucleotide sequencing. Small- and large-scale plasmid preparations were made using the alkaline lysis procedure (Maniatis, T. , et al.. Molecular cloning: a laboratory manual. Cold Spring Harbor Laboratory, Cold Spring Harbor, New York (1982) ) . Ml3mpl8 and Ml3mpl9 phage subclones to be used as templates for sequencing were generated using specific restriction subfragments determined by restriction mapping or the use of Sau3A, Taq I or Rsal-digested viral DNA pools ligated into the unique BamHl, Accl or Smal sites of M13 RF DNA, respectively. In some cases overlapping M13 deletion clones were obtained by processive Bal31 digestions from Accl, Nael or Nsil restriction sites in EcoRl-0 by the method of Poncz et al (Poncz, M., et al., Proc. Natl. Acad. Sci. USA 79:4298-4302 (1982)). Standard methods (Maniatis, T., et al.. Molecular cloning: a laboratory manual. Cold Spring Harbor Laboratory, Cold Spring Harbor, New York (1982)) were used for restriction digestions, gel electrophoresis, purification of DNA fragments from agarose gels, ligations and fill-in of 5' overhangs with Klenow fragment. Ligated M13 products were transformed into CaCl2 _ competent JM107 host cells and added to melted B top agar containing 10 1 of 100 mM IPTG, 50 1 of 2% X-gal and 200 1 of a fresh overnight JM101 culture. These contents were then plated onto B agar plates and incubated at 37°C overnight. Recombinant (clear) plaques were then used to infect 5 ml of YT media diluted 1:50 with an overnight JM101 culture and rotated at 37°C for 6 hours. The resulting cells were pelleted by centrifugation for 5 minutes at room temperature and the supernatants were removed and stored at 4°C to retain viral stocks of each recombinant clone. Using the recovered supernatants, single-stranded M13 phage DNA to be used as templates for DNA sequencing by the dideoxy-chain termination method was isolated according to instructions in the M13 Cloning/Dideoxy Sequencing Instruction Manual provided by Bethesda Research Laboratories. Recombinant Ml3mp phages were further screened by electrophoresing purified single-stranded viral DNA on 1% agarose mini-gels and selecting those templates showing reduced mobility in comparison to single-stranded Ml3mp 18 control DNA. DNA sequencing with single-stranded M13 templates was performed by the dideoxy-chain termination method (Sanger, F. S., et al., Proc. Natl. Acad. Sci. USA 74:5463-5467 (1977)) employing the modified T7 DNA polymerase, Sequenase™ (United States Biochemical Corp., Cleveland, Ohio) . A summary of the sequencing strategy is included in Figure IB. For DNA sequencing reactions, the specific step by step instructions provided with the Sequenase™ sequencing kit were employed. Briefly, single-stranded M13 templates were first annealed with the universal M13 synthetic oligonucleotide primer by incubation at 65°C for 2 minutes followed by slow cooling until the incubation temperature was below 30°C. Following the addition of proper mixtures of deoxy- and dideoxynucleotide triphosphates (dNTPs and ddNTPs, respectively), radioactively labeled deoxyadenosine 5'- (alpha-thio) triphosphate ( 35 S-dATP, 1000-1500 Ci/mmol; NEN-DuPont) and the Sequenase™ enzyme, synthesis of radioactively labeled complementary strands was initiated from the annealed primer. Four separate synthesis reactions were each terminated by the incorporation of the specific ddNTP (ddATP, ddGTP, ddTTP or ddCTP) used in each tube. Reaction products were electrophoresed through 7% polyacrylamide/50% urea/Tris-Borate-EDTA gels and the labeled chains were visualized by autoradiography. Both strands were sequenced at least once. This was facilitated by the use of 16 synthetic 17-mer olignonucleotides generated based * on previously determined sequences and substituted for the universal primer under similar reaction conditions above (0.5 pmole≥, reaction) according to the general approach described by Strauss (Strauss, E. C, et al.. Anal. Biochem. 154:353-360 (1986)). Analysis of sequence data Sequences were assembled and analyzed on an IBM personal System 2/Model 50 microcomputer utilizing the IBI/Pustell (Pustell, J., et al., Nucl. Acids. Res. 14:479-488 (1986)) and Genepro (Version 4.10; Riverside Scientific Enterprises, Seattle, WA) sequence analysis software packages or programs obtained from the University of Wisconsin Genetics Computer Group (GCG; Devereaux, J., et al., Nucl. Acids. Res. 12:387-395 (1984)) and run on a VAX 8650 minicomputer. Database searches of the National Biochemical Research Foundation-Protein (NBRF-Protein, Release 21.0, 6/89) were mdie with the GCG program FASTA (Pearson, W. R., et al., Proc. Natl. Acad. Sci. USA 85:2444-2448 (1988)) which uses: (1) a modification of the algorithm of Wilbur and Lipman (Wilbur, W. J. , et al., Proc. Natl. Acad. Sci. USA 80:726-730 (1983)) to locate regions of similarity; (2) a PAM250-based scoring system (Dayhoff, M. O. , et al., p. 345-352. In M. O. Dayhoff (ed.). Atlas of protein sequence and structure, vol. 5, Suppl. 3. National Biomedical Research Foundation, Washington, D. C. (1978)) and (3) the alignment procedure of Smith and Waterman (Smith, T. F., et al., Adv. Appl. Mathematics 2:482-489 (1981)) to join together, when possible, the highest-scoring, non-overlapping regions in order to derive an alignment and its resulting, optimized score. Dot matrix homology plots were generated by using the GCG program DOTPLOT with the output file from GCG's COMPARE. The latter creates a file of the points of similarity between two predicted amino acid sequences for which a window length of 30 and a stringency of 15 (in which conservative amino acid replacements are scored positive) were chosen. Using the GCG program GAP, specific amino acid sequences were aligned using the algorithm of Needleman and Wunsch (Needleman, S. B., et al., J. Mol. Biol. 48:443-453 (1970)); following the insertion of gaps (to maximize the number of matches) the percentage of identical and similar amino acid residues were determined. To create multiple alignments using GAP, output files of gapped MDV sequences were created following successive GAP comparisons between the MDV sequence and its homologous, sequences (in descending order of homology). These output files were used as input sequences for subsequent runs of GAP until the alignment of these gapped sequences could no longer be expanded by the addition of new gaps. Following alignment, the gapped output files were displayed and a consensus sequence calculated using the GCG program PRETTY. To achieve optimal results, in some cases manual editing was employed (using GCG's LINEUP). Results The 10,350 nucleotide DNA sequence presented (Figure 2) appears to encompass a majority of the MDV (GA) genome's unique short (Ug) region. A summary of the sequencing strategy is included in Materials and Methods and is depicted in Figure IB. This sequence spans the Ug fragments, EcoRl-0, EcoRl-I and extends to a Sail site 1.55 kbp downstream of the 3* end of BamHI-P (Figures 1A and IB) . Fukuchi et al. (Fukuchi , K., et al., J. Virol. 51:102-109 (1984)) have previously mapped the IRg-Ug junction to a 1.4 kb Bgl I fragment located in the second of five EcoRl subfragments of BamHI-A (Figure IB). Thus, the sequence presented here should lack between 2.6 and 4.0 kb of the 5'-proximal Ug region, assuming the above IRg-Ug junction location can be independently confirmed. Because the region sequenced does not extend a sufficient distance downstream of BamHl-Pi, the MDV Ug-TRg junction has not ye been precisely defined (Davison, A. J. , et al., J. Gen. Virol. 76:1759-1816 (1986)). For VZV, EHV-4 and HSV-1, this border is located about 100 bp upstream, or 1.1 and 2.7 kb downstream, respectively, of the termination codon of their respective US8 homologs (Cullinane, A. A., et al. J. Gen. Virol. 69:1575-1590 (1988); Davison, A. J. , et al. J. Gen. Virol. 76:1759-1816 (1986); and McGeoch, D. J. , et al., J. Gen. Virol. 69:1531-1574 (1988)). The overall G+C content of the region sequenced was found to be 41%, somewhat below the genomic MDV G+C values of 46% (Lee, L. F., et al., J. Virol. 7:289 (1971)) Observed frequencies of CpG dinucleotides in the whole- sequence, or in the coding regions only, did not differ significantly from those expected from their mononucleotide compositions (data not shown) . This result agrees with those obtained from alphaherpesviruses, while contrasting with those obtained from gammaherpesviruses, such as the A+T rich HVS and the G+C rich EBV, which are both deficient in CpG dinucleotides (Honess, R. W., et al., J. Gen. Virol. 70:837-855 (1989)). The region sequenced contains 9 complete ORFs likely to code for proteins (Fig. 1C, basis for names is given below). This prediction was based on: (1) homology and positional organization comparisons to other alphaherpesvirus genes and (2) presence of potential TATA and polyadenylation consensus sequences (Birnstiel, M. L., et al.. Cell 41:349-359 (1985); and Corden, B., et al.. Science 209:1406-1414 (1980)), and (3) possession of favorable contexts for translational initiation (Kozak, M. , J. Cell Biool. 108:229-241 (1989)). This identification was further guided by the observation that alphaherpesviruses such as HSV and VZV tend to contain relatively tightly packed, unspliced and generally nonoverlapping coding regions (Davison, A. J. , et al., J. Gen. Virol. 76:1759-1816 (1986); Davison, A. J. , et al., J. Gen. Virol. 76:1759-1816 (1986); McGeoch, D. J., et al., J. Gen. Virol. 69:1531-1574 (1988); McGeoch, D. J. , et al., J. Mol. Biol. 181:1-13 (1985); and McGeoch, D. J., et al., J. Gen. Virol. 68:19-38 (1987)). Such genes, especially those of the Ug regions, often share polyadenylation signals, thereby resulting in 3'-coterminal mRNA families (Rixon, F. J., et al., Nucl. Acids Res. 13:953-973 (1985)). Methods for detecting protein coding regions based on the use of MDV-derived codon frequency tables (using these and previously published MDV sequences, Binns, M. M. , et al.. Virus Res. 12:371-382 (1989); Ross, L. J. N., et al., J. Gen. Virol. 70:1789-1804 (1989); and Scott, S. D., et al., J. Gen. Virol. 70:3055-3065 (1989)) or analysis of compositional bias (using the GCG programs CODONPREFERENCE- and TESTCODE) were largely inconclusive, suggesting that MDV possesses relatively low codon and compositional biases compared to those prediced based on its mononucleotide composition. However, using the GCG program FRAMES, together with the MDV-derived codon frequency table above, the 9 identified ORFs clearly show a significantly low pattern of rare codon usage, which sharply contrasts with that observed in all other potentially translatable regions (data not shown). The predicted amino acid sequences of the predicted ORFs (beginning from the first ATG codon) are shown relative to the nucleotide sequence in Figure 2. Potential TATA sites within 400 nucleotides of the initiation codon are underlined. Proposed ORF and potential polyadenylation signal locations, identification of the -3, +4 ATG context nucleotides (Kozak, M. , J. Cell Biol. 108:229-241 (1989)), as well as the lengths, relativ molecular masses and predicted isoelectric points of the predicted translational products are shown in Table 1. A summary of MDV data is shown in Table 1, with location of ORFs, predicted polyadenylation signals utilized, translational context nucleotides, lengths, relative molecular sizes and isoelectric points of predicted translation products. a Nucleotides listed relative to -3, +4 positions, respectively; numbering begins with the A of the ATG (AUG) codon as position +1; nucleotides 5' to that site are assigned negative numbers. kin absence of post-translational modifications. c Calculated using the GCG program, ISOELECTRIC. Based on sequences that follow the predicted signal peptide cleavage site. In the absence of previous information concerning these MDV ORFs, and to simplify identification, they have been named (Figure 1C, Table 1) based on homologous relationships to HSV-1 encoded Ug ORFs (McGeoch, D. J., et al., J. Mol. Biol. 181-1-13 (1985)). When appropriate, the letters MDV will preface the homolog's name to indicate the ORF's origin. The two MDV-specific O r Fs have _een arbitrarily named SORFl and S0RF2, based on tneir location in the S component. According to the scanning model for translation, the 40S ribosomal subunit binds initially at the 5'-end of mRNA and then migrates, stopping at the first AUG (ATG) codon in a favo u rable context for initiating translation (Kozak, M. , J. Cell Biol. 108:229-241 (1989)). However, in the absence of Si nuclease and/or primer extension analysis, definitive start sites for translation cannot be accurately predicted. Nevertheless, likely start sites are listed in Table 1; these refer to the location of the first inframe ATG codon found in the major open reading frame. According to Kozak (Kozak, M. , J. Cell Biol. 108:229-241 (1989)), as long as there is a purine in position -3, deviations from the rest of the consensus only marginally impair initiation. In the absence of such a purine, however, a guanine at position +4 is essential for efficient translation. Table 1 shows that all of the ORFs, except for S0RF2, contain the important purine residue in the -3 position. Nevertheless, in the case of SORF2, a compensating guanine in position +4 is indeed present. In the case of MDV USl, two transcriptional cap sites have been tentatively identified by 5' Si nuclease protection analysis (data not shown) . These sites appear to be located 18 and 25 nucleotides downstream of a TATATAA sequence at position 200 and 207, respectively (Figure 2) Based on 3' Si data, this transcript utilizes a polyadenylation signal located just downstream of the US10 coding region (Table 1, data not shown). Comparative Northern blot analyses of the Ug region indicate that the MDV USl transcript appears to be the most prominent transcript expressed at late times (72h) post-infection when extensive cytopathic effects are observed (data not shown) . Phosphonoacetic acid inhibition studies have indicated that MDV USl, in contrast to its immediate-early HSVl USl counterpart, is regulated as a late class gene (data not shown). Using the computer program FASTA (Pearson, W. R., et al., Proc. Natl. Acad. Sci. USA 85:2444-2448 (1988)) with a K-tuple value of 1, each of the 9 predicted amino acid sequences was screened against the NBRF-Protein database (Release 21.0, 6/89), and recently published EHV-4 S segment gene sequences (11) . Optimized FASTA scores of greater than 100 were generally considered to indicate a significant degree of amino acid similarity. The results of this analysis are in Table 2. TABLE 2. PAIRUISE COHPARISONS OF HOV AND ALPHAHERPESVIRUS S COHPONENT HOMOLOGS different score when order of compar son reversed While SORFl and SORF2 do not appear to share any significant homology to any of the sequences in the database (data not shown), apart from MDV US3, the other six ORFs (MDV USl, 10, 2, 6, 1 , and 8; Tables 1, 2) were found to be homologous to alphaherpesvirus S segment genes. exclusively (Table 2). Because the US3 ORF represents'a member of the serine-threonine protein kinase superfamily (Hanks, S. K. , et al.. Science 241:42- (1988)), a relativel * large number of scores above 150 were obtained. Nevertheless, these scores were 3-4 fold lower than those obtained in comparisons with US3 homologs of HSV, PRV and VZV. To compare with previously established alphaherpesvirus S segment homologies, all possible FASTA comparisons between the seven groups of alphaherpesvirus-related sequences are included. The program GAP was used in similar pairwise comparisons to generate optimal alignments in order to determine the total percentage of identical and similar amino acids shared by the two sequences. As shown in Table 2, homology comparisons between MDV S segment ORFs and their alphaherpesvirus counterparts were comparable to those previously observed between the other alphaherpesvirus S segment homologs themselves. In some cases MDV ORFs were found to be more related to alphaherpesvirus homologs than those same homologs were to their other alphaherpesvirus counterparts (corapare MDV/EHV-4 vs. HSV-l/EHV-4 USl and MDV/EHV-4 vs. HSV-l/EHV-4 US10 homologies). Moreover, despite the fact that VZV lacks US2 and US6 homologs, MDV, although formally considered a gammaherpesvirus, clearly does possess US2 and US6 homologs. The results of limited multiple alignments for each of the seven homologs in which areas showing best conserv * ion are depicted in Figure 3A. Dot matrix homology plots depicting overall homologies between selected MDV-alphaherpesvirus S segment homolog comparisons are included in Figure 3B. (Using a sliding window 'length of 30 amino acids, in which points are generated where at least 15 amino acids are found identical or similar) . The resulting diagonals illustrate the regions showing greatest conservation. Such regions include and in some cases extend upon those regions depicted in Figure 3A. More sensitive attempts to identify other related, proteins not detected with FASTA were made using the GCG programs PROFILE and PROFILESEARCH. Use of these programs permit database comparisons which rely on information available from structural studies and, in this case, from information implicit in the alignments of related S component ORFs (including MDV sequences using GAP) (Gribskov, M., et al., Proc. Natl. Acad. Sci. USA 84:4355-4358 (1987)); nevertheless, such analyses failed to extend upon the groups of related proteins described here. Herpesvirus glycoprotein homologs have generally been found to contain similar patterns of conserved cysteine residues. In comparing the gB homologs of seven different herpesviruses included in the alpha-, beta- and gammaherpesvirus subclasses, there is complete conservation of 10 cysteine residues (Ross, L. J. N., et al., J. Gen. Virol. 70:1789-1804 (1989)). HSV-1 US6 (gD) contains 7 cysteine residues: six appear critical for correct folding, antigenic structure and extent of oligosaccharide processing (Wilcox, W. C, et al., J. Virol. 62:1941-1947 (1988)). Not only is this same general pattern of cysteines conserved in the gD homologs of HSV-2 (McGeoch, D. J., et al., J. Gen. Virol. 68:19-38 (1987)) and PRV (Petrovskis, E. A., et al., J. Virol. 59:216-223 (1986)), but they are conserved in the MDV gD homolog as well (full alignment not shown). Figure 3A depicts portions of cysteine conservation patterns observed among the US6 (gD), US7 (gl), and US8 (gE) homologs (in which case 4, 3, and 6 conserved cysteine residues are shown, respectively). While the MDV, VZV, PREV, and EHV-1 US8 homologs (Audonnet, J.-C, et al., J. Gen. Virol. 71:2969-2978 (1990); Davison, A. J., et al., 'J. Gen. Virol. 76:1759-1816 (1986); and Petrovskis, E. A., et al., J. Virol. 60:185-193 (1986)) al share a similar pattern of four conserved cysteine residues near their amino termini, the HSV-1 and -2 counterparts carry only two of these (McGeoch, D. J. , J. Gen. Virol. 71:2361-2367 (1990); data not shown). It is quite possible that the unique pattern of four conserved cysteines could facilitate the formation of different secondary and tertiary structures which might impart important functional consequences. These might be reflected by findings which show that HSV-1 gE has Fc receptor activity (Johnson, D. C, et al., J. Virol. 62:1347-1354 (1988)), while its PRV and VZV counterparts do not (Edson, C. M. , et al., Virology, 161:599-602 (1987); and Zuckerman, F. A., et al., J. Virol. 62:4622-4626 (1988)). Careful inspection of the N-terminal regions of the MDV gD, gl and gE homologs has revealed that they contain the three basic building blocks of signal peptide sequences: a basic, positively charged N-terminal region (n-region) , a central hydrophobic region (h-region), and a more polar terminal region (c-region) that seems to define the cleavage site (von Heijne, G. J. Mol. Biol. 184:99-105 (1985)). Using a recently improved method for predicting signal sequence cleavage sites (von Heijne, G. Nucl. Acids Res. 14: 4683-4690 (1986)), Table 3 shows the likely position of these sites, the location of the hydrophobic transmembrane and charged cytoplasmic domains near the C-terminal end and the location of potential N-glycosylation sites. Table 3 shows MDV Ug glycoprotein data on predicted signal peptide cleavage sites and locations of transmembrane and cytoplasmic domains and potential N-glycosylation sites (with respect to the ATG initiation codon) . n Like the other gl homologs, MDVs counterpart contains a relatively long cytoplasmic domain. However, in contrast to the other gD homologs, MDV gD's signal peptide contains a relatively long n-region (18 residues), that is unusually highly charged (+4; Figure 2) considering an _._ overall mean value of +1.7 among eukaryotes, which generally does not vary with length (von Heijne, G, J. Mol. Biol. 184:99-105 (1985)). Although a more distal methionine codon exists directly before the initiation codon (as in the PRV gD homolog, Petrovskis, E. A., et al., 20 J. Virol. 59:216-223 (1986)) the scanning model for translation (Gribskov, M., et al., Proc. Natl. Acad. Sci. USA 84:4355-4358 (1987)) favors usage of the more 5'-proximal initiation codon (at position 5964, Figure 2). Further support is based on an overall translation context 25 that appears at least as good as, if not better than, the one corresponding to the downstream ATG. Despite such a prediction, a possible mRNA cap site location between the two ATG sites, which would preclude such a prediction, cannot be ruled out at this point. 30 One final point concerning MDV gD requires mention. Using the 10,35.0 nucleotide DNA sequence as a probe for screening the GenBank (62.0, 12/89) and EMBL (19.0, 5/89) nucleic acid databases with the computer program FASTA (K-tuple=6) , an optimized score of 1027, 35 corresponding tp 91.5% nucleotide identity in a 342 bp overlap between MDV gD coding sequences (6479-6814; aa#173-aa#284; Figure 2) and a previously reported 467 bp MDV DNA segment (Wen, L.-T. , et al. , J. Virol. 62:3764-3771 (1988)). The latter sequence has been reported to contain a 60 bp segment protected against DNAse digestion by binding of a 28kD MDV nuclear antigen (MDNA) expressed only in "latently" infected MDV-transformed lymphoblastoid cells. In view of similarities between MDV and VZV, these authors, suggested that MDNA may function in a manner analogous to that of EBNA-1 in immortalizing primate cells. In their report. Wen et al. (Wen, L.-T., et al. , J. Virol. 62:3764-3771 (1988)) mapped the MDNA binding site to the same EcoRl subfragment of BamHI-A in which MDV gD is located (EcoRI-I, Figure 1). Although our sequence covering this region is consistent with a complete, uninterrupted ORF containing all the characteristic features of a glycoprotein, and showing significant homology to HSV gD, their sequence contains about 140 bases of 5'-proximal sequence unrelated to any determined from our 5.3 kbp EcoRl-I fragment or its adjoining 3.5 kb sequences. The remaining 327 bp sequence (which contains the putative nuclear antigen binding site) while clearly resembling our gD coding sequence, upon computer translation fails to yield any ORF longer than 30 aa. Discussion Recent data have shown that despite MDV's classification as a gammaherpesvirus, based on lymphotropic properties shared with other members of this subfamily, its genome structure (Cebrian, J. , et al., Proc. Natl. A^ad. Sci. USA 79:555-558 (1982); and Fukuchi, K., et al., J. Virol. 51:102- " O9 (1984)) and genetic organization of primarily its U L region (Buckmaster, A. E., et al., J. Gen. Virol. 69:2033-2042 (1988)) iore closely resembles that of the neurotropic alphaherpesviruses. Moreover, in cases where polypeptide sequences were found conserved among the three herpesvirus subfamilies (e.g. \}-_ genes), significantly higher homology scores were consistently observed against the respective alpha- rather than beta- or gammaherpesvirus counterparts (Davison, A. J., et a " J. Gen. Virol. 67:597-611 (1986); Buckmaster, A. E. , et al., J. Gen. Virol. 69:2033-2042 (1988); Ross, L. J. N. , et al., J. Gen. Virol. 70:1789-1804 (1989); and Scott, S. D., et al., J. Gen. Virol. 70:3055-3065 (1989)). Alphaherpesvirus S segment genes have previously been found to be unique to members of this taxonomic subfamily (Davison, A. J., et al., J. Gen. Virol. 68:1067-1079 (1987); and Davison, A. J., et al., J. Gen. Virol. 67:597-611 (1986)). The identification of seven MDV homologs of alphaherpesvirus S segment genes in this study is consistent with the idea that MDV shares a closer evolutionary relationship with alphaherpesviruses than gammaherpesviruses. This is further supported by dinucleotide frequency analysis which fails to show a lack of CpG suppression as observed among all gammaherpesviruses thus far studied (Efstathiou, S., et al., J. Gen. Virol. 71:1365-1372 (1990); and Honess, R. W. , et al., J. Gen. Virol. 70:837-855 (1989)). The above situation resembles a similar one observed with human herpesvirus-6 (HHV-6), in which case its T-lymphotropism suggested provisional classification as a gammaherpesvirus (Lopez, C, et al., J. Infect. Dis. 157:1271-1273 (1988)). However, subsequent genetic analysis has shown a greater relatedness between HHV-6 and the betaherpesvirus, human cytomegalovirus (HCMV; Lawrence, G. L., et al., J. Virol. 64:287-299 (1990)). A comparison of the genetic organization of alphaherpesvirus S segment genes is presented in Figure 4. The organization of these genes in some cases vary greatly in overall length, organization and degree of homology. Nevertheless, the overall gene layouts displayed are consistent with a model to account for the divergence of alphaherpesviruses from a common ancestor by a number of homologous recombination events which result in expansion or contraction of the inverted repeat regions and a concomitant loss or gain of U s gene(s). In the case of VZV, six S segment homologs are lacking compared to HSV-1 (US2, US4, US5, US6, USll, US12). Some genes, such as the USl homologs, show particular sequence and length divergences. Compared to HSV-1, the MDV, VZV and EHV-4 USl homologs lack approximately 120 aa of sequence comparable to the 5'-proximal portion of HSV-1 USl (alpha 22) Based on Northern blot analysis, Si nuclease protection analysis and phosphonoacetic acid inhibition studies, in contrast to its relatively uncharacterized immediate-early HSV-1 counterpart, the MDV USl gene appears to be regulated as an abundantly expressed late class gene (data not shown). In contrast to the other alphaherpesviruses, MDV contains two apparently MDV-specific ORFs. Moreover, the MDV Ug region appears to contain approximately 2.6 to 4.0 kb of additional 5*-proximal sequences. Based on a comparison of Figure 4 and consideration of the expansion-contraction recombination scheme, it appears likely that there are additional MDV-specific Ug genes. Since MDV has long been regarded as a gammaherpesvirus, much of the previous work interpreting their properties has proceeded by analogy with the association between EBV and B cells (Nonoyama, M. p. 333-341. In B. Roizman (ed. ) , The herpesviruses, vol. 1. Plenum Press (1982); and Wilbur, W. J. , et al., Proc. Natl. Acad. Sci. USA 80:726-730 (1983)). Because of a closer genetic relationship to the alphaherpesviruses, and keeping in mind the analysis of HHV-6 above, we agree with Lawrence et al. (Lawrence, G. L. , et al., J. Virol. 64:287-299 (1990)) that the lymphotropic properties of MDV and HVT are unlikely to be determined by molecules homologous to EBV and that a delineation of molecular differences between MDV and the neurotropic alphaherpesviruses would be more fruitful in expl_ ning the observed biological differences than employing analogies based on properties of gammaherpesviruses such as EBV and HVS. To account for such differences, the MDV Ug region may be particularly important. With few exceptions, each HSV-1 L component gene possesses an equivalent in VZV (McGeoch, D. J., et al., J. Gen. Virol. 69:1531-1574 (1988)); a considerable number of these are related to beta- and gammaherpesvirus genes as well (29 of 67 EBV counterparts to VZV U L genes; Davison, A. J., et al., J. Gen. Virol. 68:1067-1079 (1987)). In contrast, the S segments of HSV-1 and VZV differ significantly in size and appear to be among the least related parts of the two genomes (Davison, A. J. , et al., J. Gen. Virol. 67:597-611 (1986; and Davison, A. J., et al., J. Gen. Virol. 64:1927-1942 (1983)). Recent studies have shown that 11 of 12 open reading frames contained in the HSV-1 S component are dispensable for growth in cell culture (Longnecker, R. , et al., Proc. Natl. Acad. Sci. USA 84:4303-4307 (1987); and Weber, P. C, et al.. Science 236:576-579 (1987)). The maintenance and evolution of such a dispensable gene cluster suggests the presence of functions relevant to the viruses survival in its specific ecological niche in the natural or laboratory animal host, rather than the presence of functions necessary for replication (Longnecker, R., et al., Proc. Natl. Acad. Sci. USA 84:4303-4307 (1987); and Weber, P. C, et al.. Science 236:576-579 (1987)). Consistent with such a hypothesis are findings that HSV mutants carrying different S component gene-specific deletions were significantly less pathogenic and exhibited a reduced capacity for latency establishment in mice (Meignier, B. , et al.. Virology 162:251-254 (1988)). In regard to the latter, there is evidence suggesting that RNA transcribed from the HSV Ug region may be involved in the establishment and maintenance of an in_ vitro latency system employing human fetus lung fibroblast cells (Scheck, A. C, et al., Intervirology 30:121-136 (1989)). Taken together, the above evidence suggest(s) potentially important role(s) for MDV's Ug genes in tissue tropism, latency, and/or induction of cell transformation. A consideration of the three gD, gl and gE homologs identified in this invention raises two other questions of relevance to future vaccine development. The 11 HSV-1 Ug region genes dispensible for growth in tissue culture described above include l^SV-l US7 (gl) and US8 (gE) (Longnecker, R., et al., Proc. Natl. Acad. Sci. USA 84:4303-4307 (1987); and Weber, P. C, et al.. Science 236:576-579 (1987)). Assuming the MDV homologs have the same properties, these genes may be useful as sites for insertion of foreign genes. Further the same two MDV homologs, and especially US8 (gE), may very likely be involved in the pathogenicity-related issues introduced above. Specifically HSV's gE seem to play a role in HSV-1's ability to establish lethal infections and latency in mice (Meignier, B., et al.. Virology 162:251-254 (1988)) Further, the gl and gE homologs of PRV of swine play a clear role in PRV virulence for 1-day-old chickens and young pigs (Mettenleiter, Thomas C, et al.. Journal of Virology, p. 4030-4032 (Dec. 1987)). Assuming the same holds true for the MDV US7 (gl) and US8 (gE) homologs, it may be possible to inactivate one or both of these genes from very virulent MDV isolates which cause outbreaks not prevented by current vaccines, and thereby creating an attenuated vaccine viruses more closely related to field virus causing disease outbreaks. A further consideration of the three (gD, gl and gE) homologs identified in this invention raises another interesting question. Fully enveloped infectious MDV virions are only known to be produced in feather follicle epithelial cells (Payne, L. N. p. i47-431. Iin B. Roizman (ed.), The herpesviruses, vol. 1. Plenum Press (1982)). Because of this, MDV studies have had to rely on limited fibroblast cell cultures which only promote the spread of cell-associated infections in_ vitro. Over the last 20 years, studies aimed at identifying immunogenic surface antigens have relied on this iτ__ vitro culture system and altogether only two glycoprotein antigens (A antigen/gC homolog; B antigen) have been routinely identified and characterized (Binns, M. M. , et al.. Virus Res. 12:371-382 (1989); Coussεns, P. M., et al., J. Virol.. 52:2373-2379 (1988); Isfort, R. J., et al., J. Virol. 59:411-419 (1986); Isfort, R. J. , et al., J. Virol. 57:464-474 (1986); and Sithole, I., et al., J. Virol. 62:4270-4279 (1988)). This is despite findings of three MDV gD, gl and gE homologs of the present invention and two additional glycoprotein homologs (gB and gH, Buckmaster, A. E. , et al., J. Gen. Virol. 69:2033-2042 (1988); and Ross, L. J. N., et al., J. Gen. Virol. 70:1789-1804 (1989)). While immune chicken sera (ICS) from naturally infected birds is likely to react with many, if not all, MDV-encoded surface antigens, this complex polyclonal sera would only be useful to the extent that antigen expression/processing in semi-productive cell culture resembles that in feather follicle epithelial cells. Northern blot analysis using MDV gD-specific probes suggests that MDV gD mRNA is either not expressed or poorly expressed in DEF cells at a time when extensive cytopathic effects are observed (data not shown). In light of the fact that VZV lacks a gD homolog and is strongly cell-associated, it will be interesting to see whether the block in MDV virion formation in primary avian fibroblast cells is found to correlate with lack of expression (in these cells) of a glycoprotein, such as gD, and/or some other S component gene(s). Because the protection against MD conferred by attenuated MDV strains (serotype 2) or HVT (serotype 3) appears to have an immunological basis, there is considerable interest in identifying common antigens. In view of this invention identifying seven MDV Ug homologs to Ug genes of HSV (the latter of which is clearly less related to MDV than HVT is), it would be surprising if the previous report showing lack of homology between MDV-HVT Ug regions (Igarashi, T. , et al.. Virology 157:351-358 (1987)) were proven correct. Such negative results may reflect the limitations regarding homology estimates based on hybridization, rather than sequence analysis studies. Example 2 shows the molecular cloning of a construct containing the DNA encoding the complete MDV US7 (gl) gene and part of the MDV US8 (gE) gene. As can be seen, this is accomplished using segments of DNA spanning the gl and part of the gE coding region. Example 2 MOLECULAR CLONING OF A CONSTRUCT CONTAINING THE DNA ENCODING THE COMPLETE MDV US7 (gl) and PART OF MDV US8 (gE) Construction of a recombinant clone (pKS-MDgIl.59) containing the complete MDV US7 (gl) coding sequence and a portion of the MDV US8 (gE) coding sequence requires two preexisting MDV clones, pKS-MDgDl.75 and pl9Pl (Fig. 5). pKS-MDgDl.75 is a recombinant plasmid containing the 1.75 kbp Ncol-Sstll subfragment of MDV EcoRl-I ligated into the Smal-Sst II site of the cloning vector, pBluescript KS-. This clone contains the complete MDV US6 (gD) coding sequence and additional sequences at the 3* end which code for the first 39 amino acids (aa) of MDV gl. pl9Pl is a recombinant plasmid containing the 1.5 kbp BamHI-Pi subfragment of MDV cloned into the unique BamHl site of pUCl9. This clone contains the entire MDV gl coding sequence, except for the first 9 aa of its signal sequence. In addition, at the 3' end, pl9Pl contains the first 104 aa of the MDV US8 (gE) coding region. To generate pKS-MDgll.59, pKS-MgDl.75 is first cut with Hindi, which cuts once in the multiple cloning site of the pBluescript vector and once about 180 bp upstream of the insert's Sstll terminus. This results in two fragments: one fragment (1.6 kbp) consists primarily of insert sequences encoding MDV US6 (gD) ; the larger fragment (3.1 kbp) consists of pBluescript vector sequences, in addition to about 180 bp which encode the N-terminus of MDV gl. The 3.1 kb fragment is gel purified and self-ligated by way of the two Hindi ends. The resulting recombinant plasmid, pKS-MDgl0.18, is then cut with Sstl (in the multiple cloning site, just downstream of the Sstll site). Prior to subsequent digestion with Sstll, the cohesive Sstl ends is made blunt-ended with T4 DNA polymerase. The resulting 3.1 kbp Sstll-Sstl (blunt) fragment of pMDglO.18 is gel purified and used in the final ligation step to create pKS-MDgIl.59. While the enzymatic manipulations of pKS-MDgDl.75 and pKS-MDgl0.18 are taking place, pl9Pl is cut with Hindlll, which cuts just downstream of the partial MDV US8 (gE) coding sequence in the multiple cloning site of pUCl9. Prior to digestion with Sstlld, the cohesive Hindlll ends is made blunt-ended using Klenow fragment. The smaller Sstll-Hindlll (blunt) fragment (1.4 kbp) contains a majority of the MDV US7 (gl) coding sequence, in addition to 312 nucleotides at the 3* end which code for the 5' end of MDV gE. This 1.4 kbp Sstll-HindllKblunt) fragment is gel purified and ligated to the 3.1 kbp Sstll-SstKblunt) fragment of pKS-MDgD0.18. The resulting recombinant, pKS-MDgIl.59, contains the complete coding sequence for MDV gl and a portion of the N-terminal gE coding sequence. Digestion of pKS-MDgIl.59 with Kpnl yields two fragments; the smaller 1.15 kbp fragment contains the complete coding sequence for MDV gl. Example 3 shows molecular subcloning of a construct containing the complete MDV US8 (gE) gene. Example 3 MOLECULAR CLONING OF A CONSTRUCT ENCODING THE COMPLETE MDV US8 (gE) Construction of a recombinant clone (pl8-MDgE2.53) containing the complete MDV US8 (gE) coding sequence requires a clone other than the BamHl or EcoRl clones used previously. GA strain clone GA-02, an EMBL-3 clone containing a partially digested MDV Sail insert, which contains BamHI-A, -Pi, and additional 5' and 3' flanking sequences (kindly provided by P. Sondermeier, Intervet Intl. B. V. , Boxmeer, The Netherlands) was used to extend analysis 3' of the EcoRl-I and BamHl-Pl fragments. Smaller Sail subfragments located at the 3' end of this phage clones MDV insert were gel purified and ligated to pUClδ linearized to Sail (pSPl8-A, pSPl8-B, and pSPl8-C, Fig. IB). The pUClδ subclone, pSPl8-A contains the entire MDV US8 (gE) coding sequence and is designated pl8-MDgE2.53 for ATCC deposit purposes. Index of definition of letters in Figure 2. Table 4 showing the amino acids with both their single letter and three letter symbols. TABLE 4 Alanine Cysteine Aspartic Acid Glutamic Acid Phenylalanine Glycine Histidine Isoleucine Lysine Leucine When the DNA segments encoding glycoproteins gl and gE are altered by insertional, site-directed or deletion utagenesis, the pathogenicity of the MDV may be reduced. Also, the segments of DNA encoding the non-essential gl and gE can be used as insertion sites for segments of foreign DNA which encode proteins that are antigenically active for the purpose of producing a recombinant vaccine. ATCC Deposit The gene for MDV US6 (MDV gD) has been deposited in a plasmid (phagemid) pKS-MDgDl.75, as ATCC 40855, with The American Type Culture Collection, Rockville, MD, 20852, USA. The gene for MDV US7 (MDV gl) has been deposited in a plasmid (phagemid) pKS-MDgIl.59, as ATCC 75040, with The American Type Culture Collection, Rockville, MD, 20852, USA. The gene for MDV US8 (MDV gE) has been deposited in a plasmid pl8-MDgE 2.53, as ATCC 75039, with The American Type Culture Collection, Rockville, MD, 20852, USA. Atta'ched are Sequence Listings for Sequence ID NOS. 1, 2 and 3 as previously described in the application. APPENDIX I (1) GENERAL INFORMATION: (i) Applicants: Leland F. Velicer, Peter Brunovskis, and Paul Coussens (ii) Title of Invention: Marek's Disease Herpesvirus DNA Segment Encoding Glycoproteins gD, gl and gE (iii) Number of Sequences: 3 (iv) Correspondence Address: (A) Addressee: Ian C. McLeod (B) Street: 2190 Commons Parkway (C) City: Okemos (D) State: Michigan (E) County: Ingham (F) Zip: 48864 (v) Computer Readable Form: (A) Medium Type: 1.44 Mb 3 1/2" floppy diskette (B) Computer: IBM PS2, Model 50 (C) Operating System: MS-DOS 5.0 (D) Software: PC-Write 3.02 (viii) Attorney/Agent Information: (A) Name: Ian C. McLeod (B) Registration No. : 20,931 (C) Reference/Docket Number: MSU 4.1-132 (ix) Telecommunication Information: (A) Telephone: (517) 347-4100 (B) Telefax: (517) 347-4103 (2) Information for SEQ ID NO: 1 (i) Sequence Charateristics: (A) Length: 10,350 base pairs (B) Type: nucleic acid (C) Strandedness: double (D) Topology: linear (ii) Molecule Type: genomic DNA (iii) HYPOTHETICAL: Yes (v) ANTI-SENSE: No (vi) ORIGINAL SOURCE: (A) Organism: MDV, GA strain (vii) IMMEDIATE SOURCE: (A) Library: genomic (xi) SEQUENCE DESCRIPTION: SEQ ID NO:l: GAATTCCTTG AAATTGGAGT GAAATCTTTA GGGAGGGAGG TTTACCATTG TGGAGAATAT 60 ATAGAGCAAG TAGTACATTA GGGGCTGGGT TAAAGACCAA GTAATTTTTG ACCGGATATC 120 ACGTGATGTA AATTCTAGCA ATTATTGTTC CTAGCAGAAG ATAAAAGCTG GTAGCTATAT 180 AATACAGGCC AAAGTCTCCA AATTACACTT GAGCAGAAAA CCTGCTTTCG GCTCCATCGG 240 AGGCAAC ATG AGT CGT GAT CGA GAT CGA GCC AGA CCC GAT ACA CGA TTA 289 Met Ser Arg Asp Arg Asp Arg Ala Arg Pro Asp Thr Arg Leu 1 5 10 TCA TCG TCA GAT AAT GAG AGC GAC GAC GAA GAT TAT CAA CTG CCA CAT 337 Ser Ser Ser Asp Asn Glu Ser Asp Asp Glu Asp Tyr Gin Leu Pro His 15 20 25 30 TCA CAT CCG GAA TAT GGC AGT GAC TCG TCC GAT CAA GAC TTT GAA CTT 385 Ser His Pro Glu Tyr Gly Ser Asp Ser Ser Asp Gin Asp Phe Glu Leu 35 40 45 AAT AAT GTG GGC AAA TTT TGT CCT CTA CCA TGG AAA CCC GAT GTC GCT 433 Asn Asn Val Gly Lys Phe Cys Pro Leu Pro Trp Lys Pro Asp Val Ala 50 55 60 CGG TTA TGT GCG GAT ACA AAC AAA CTA TTT CGA TGT TTT ATT CGA TGT 481 Arg Leu Cys Ala Asp Thr Asn Lys Leu Phe Arg Cys Phe lie Arg Cys 65 70 75 CGA CTA AAT AGC GGT CCG TTC CAC GAT GCT CTT CGG AGA GCA CTA TTC 529 Arg Leu Asn Ser Gly Pro Phe His Asp Ala Leu Arg Arg Ala Leu Phe 80 85 90 GAT ATT CAT ATG ATT GGT CGA ATG GGA TAT CGA CTA AAA CAA GCC GAA 577 Asp lie His Met lie Gly Arg Met Gly Tyr Arg Leu Lys Gin Ala Glu 95 100 105 110 TGG GAA ACT ATC ATG AAT TTG ACC CCA CGC CAA AGT CTA CAT CTG CGC 625 Trp Glu Thr lie Met Asn Leu Thr Pro Arg Gin Ser Leu His Leu Arg 115 120 125 AGG ACT CTG AGG GAT GCT GAT AGT CGA AGC GCC CAT CCT ATA TCC GAT 673 Arg Thr Leu Arg Asp Ala Asp Ser Arg Ser Ala His Pro lie Ser Asp 130 135 140 ATA TAT GCC TCC GAT AGC ATT TTT CAC CCA ATC GCT GCG TCC TCG GGA 721 lie Tyr Ala Ser Asp Ser lie Phe His Pro lie Ala Ala Ser Ser Gly 145 150 155 ACT ATT TCT TCA GAC TGC GAT GTA AAA GGA ATG AAC GAT TTG TCG GTA 769 Thr lie Ser Ser Asp Cys Asp Val Lys Gly Met Asn Asp Leu Ser Val 160 165 170 GAC AGT AAA TTG CAT TAA CTATCCAGAC TTGAAGAGAA AGCTCTTATT 817 Asp Ser Lys Leu His End 175 ATATAATTTT AATTGTTAGA CATAGAGCCG ACATTCTTTG ATCTATCTAA TGAGATAAAA 877 TAATAGATTT TGGATTTATT TGTCATGATC TGTTGCAACA AACGCTGACC CCCCCCATCC 937 ATGAAGGGGC GTGTCAAATA ACGTGTTGCC TTTTTGTTGT ATATGAAGAT ATTTAATGTG 997 GCGTTGAGCC TAATGAGAGG AGAACGTGTT TGAATACTGG AGACGAGCGC CGTGTAAGAT 1057 TAAAACATAT TGGAGAGGT ATG GCC ATG TGG TCT CTA CGG CGC AAA TCT 1106 Met Ala Met Trp Ser Leu Arg Arg Lys Ser 1 5 10 AGC AGG AGT GTG CAA CTC CGG GTA GAT TCT CCA AAA GAA CAG AGT TAT 1154 Ser Arg Ser Val Gin Leu Arg Val Asp Ser Pro Lys Glu Gin Ser Tyr 15 20 25 GAT ATA CTT TCT GCC GGC GGG GAA CAT GTT GCG CTA TTG CCT AAA TCT 1202 Asp lie Leu Ser Al∑ 7 Gly Glu His Val Ala Leu Leu Pro Lys Ser 30 35 40 GTA CGC AGT CTA GCC AGG ACC ATA TTA ACC GCC GCT ACG ATC TCC CAG 1250 Val Arg Ser Leu Ala Arg Thr lie Leu Thr Ala Ala Thr lie Ser Gin 45 50 55 GCT GCT ATG AAA GCT GGA AAA CCA CCA TCG TCT CGT TTG TGG GGT GAG 1298 Ala Ala Met Lys Ala Gly Lys Pro Pro Ser Ser Arg Leu Trp Gly Glu 60 65 70 ATA TTC GAC AGA ATG ACT GTC ACG CTT AAC GAA TAT GAT ATT TCT GCT 1346 lie Phe Asp Arg Met Thr Val Thr Leu Asn Glu Tyr Asp lie Ser Ala 75 80 85 90 TCG CCA TTC CAC CCG ACA GAC CCG ACG AGA AAA ATT GTA GGC CGG GCT 1394 Ser Pro Phe His Pro Thr Asp Pro Thr Arg Lys lie Val Gly Arg Ala 95 100 105 TTA CGG TGT ATT GAA CGT GCT CCT CTT ACA CAC GAA GAA ATG GAC ACT 1442 Leu Arg Cys lie Glu Arg Ala Pro Leu Thr His Glu Glu Met Asp Thr 110 115 120 CGG TTT ACT ATC ATG ATG TAT TGG TGT TGT CTT GGA CAT GCT GGA TAC 1490 Arg Phe Thr He Met Met Tyr Trp Cys Cys Leu Gly His Ala Gly Tyr 125 130 135 TGT ACT GTT TCG CGC TTA TAT GAG AAG AAT GTC CGT CTT ATG GAC ATA 1538 Cys Thr Val Ser Arg Leu Tyr Glu Lys Asn Val Arg Leu Met Asp He 140 145 150 GTA GGT TC -.CA ACG GGC TGT GGA ATA AGT CCA CTC CCC GAA ATA GAG 1586 Val Gly Ser Ala Thr Gly Cys Gly He ^er Pro Leu Pro Glu He Glu 155 160 165 170 TCT TAT TGG AAA CCT TTA TGT CGT GCC GTC GCT ACT AAG GGG AAT GCA 1634 Ser Tyr Trp Lys Pro Leu Cys Arg Ala Val Ala Thr Lys Gly Asn Ala 175 180 185 GCA ATC GGT GAT GAT GCT GAA TTG GCA CAT TAT CTG ACA AAT CTT CGG 1682 Ala He Gly Asp Asp Ala Glu Leu Ala His Tyr Leu Thr Asn Leu Arg 190 195 200 GAA TCG CCA ACA GGA GAC GGG GAA TCC TAC TTA TAA CTAATCGCAC 1728 Glu Ser Pro Thr Gly Asp Gly Glu Ser Tyr Leu End 205 210 AATTATTAAT AGGATTTTAG GAAAAACTGC TACTAACGTT GTTTAAATAA TAAAATTTTA 1788 TTTTCAATAA GGCATTACAG TGTTGTCATG ATTGTATGTA TTATATGGGG TATGCATGAG 1848 GATTACTTCG ATTGAAACTT TGTCTAAATG TCTGTAGGAT TTTACTATTC ATTAGTCTGG 1908 ' ATCGAGGCGG ACGTAAATGG AGATTGCGGC AAATGTAGGG GTGCTGGTAC ATAAGACCTC 1968 CAACATCCAT TCGACTCATC GGCCTGCGTC CAAATGGATA TGTTGATGTA CCTTGTAAAG 2028 TTATGACATT AGAAGATCGA TGGTGAATAG TGGGATCTAT ATCCATGCTA TTCTCAATAT 2088 TGCATGATAT GCAATGTTCC CGGTTAGGTT TGATAAGATC ATGTATGGTT CTATAATACA 2148 ACTCCTCTTC AGAAGAATCA TTTATTTTAT GTCCACTGTC CTTGGATATT CCAGTTTCTG 2208 TCAATCGATT CGCTTGCATT TGCGTGCAGC ATGTCTTGAT GGCATTTCCT ATGCTATCAT 2268 CCGGCAGGCC TAAGGGTGTT CTATACTCGC ACACAGGTAG AGCAAGAACC ACGGCATATC 2328 GAGCTACCTC TATTGCCCCG CTAAGGACAT TTCTTGCAGA CTGTATTGTC ATGAACATAT 2388 TTCGTGTATT GTGTCGATCA TAACCCTTGT TGATTCCTAT GGAAAGCATT GTGGTCCAGT 2448 TTTCCAGATG AAATGAAAAC AATGCGGGCA AAAATGGTCC CACCTGTTTC ATCTTCAATG 2508 CATCTCTCAC ATCCCAAGTT CTATAGAATA TTCTCCACTG ACCAGTTTCG GTAAGATCAG 2568 TTTCTGTAAA ATTTGTGATA GTTTCAATCG AAAACATTTT GTCCATCATG GCAAAAAATC 2628 TATAGGCAGA CCAGATAACC ATTTGACACC ACATATCCTT GTGTATATCA AACGATGTAA 2688 TAGATCCCTC GTTAGTAGAT ATGGTACATA AAAGGCCTAA TCTCTCTCGG GCTTCCATAC 2748 ATTGAACGAT TCCTTCTGTG AATTCATCAA CAACCACATG CCAAAAATTT ACATTAGTAA 2808 TCTTTCTCGG TGGCTTACCA AATCGTCCTC TTGGTATATC CATATCATCG AACATTGTAG 2868 CATTGACTCT GCTCATCGTT GTCTTTCAAA TGCGCTCGAT TGTTGAATCT CTCCTGATGT 2928 TAGAAGTATA TGGAAGATAG CCTGGATACA TAAGTGATCT AGAAGGGTTT GTTATTGCAC 2988 TAATATACAA ATTATACGTG ACACTATAGC GACGGTTGTA GCGATGCACC TAATCGTAAT 3048 GTGTATACGC CCCATCATGT AATTATATCT AATTGGTAGC AAGTAGGTCT GTCGAATAAC 3108 AGCTAATGAC TACCGGCTCT ACATTTTTTC TGTATTCGTG ACTTTCCTGT CGCAGTGTAA 3168 CGAACCGGAA TTGCAATCGC ATCTCTATCT TCTTTCTTGC AACATTTTCC ACAACAGAAT 3228 AATCTGCCGG GTGTACTACT CATTTGAGGT GGTTCGATTT CCGGAGGTTT TAGAGGATTG 3288 GGTGGGGACC CGAGGATTTT GTATACACAT ACCATATCAC TGTCGCAAAA ATGCGCTCTA 3348 TCTTCTGGGG TGTCGAACTT CGGTTCCCAT GTAGATGTCA AGAGAGTTTG AATATTGTCG 3408 GGAATGGCCC ACGGCATACC GGACCAGGTC CCAGACACTT TGATTGCAAG TAACCTTTTT 3468 GGCAAAGGAA TACATTCGAG CGCAATGGCA CATATATCTG CCGCCCCAAC TATCCACAAG 3528 CTATGTGGAG CATTACCAGA AACTTCAGAT TCCAACATCA AATATCCAGA TAGAACATCC 3588 TGCCATTCTG TGGAACATCC TGCAACATCT TCAAATAGCC GCACTATAAA CGAATCCCTA 3648 GTTCCGGCCA ATCCGGTACC ACGAACTCCA GTTCCATCTG GTGGCTTTGT CCTTACTATC 3708 GGTCGATGTT GCCGAGGAAG AATTAACATG GGTTTGGCAA AACGGAATAG GTCTGCAGCT 3768 CTGGCGATTA TGGGCACACC CACATCATCC TGTATTTGTT CCATACATTG CTTTATAAGG 3828 AATATCCATA AAGTAGATGC AGCATCTCTA GATCTTCCTG GCAATCGATC GCATTCATCT 3888 AGAAGTGTGA CTATAGTTAT CATGGACACA CCCATCTTCA CCTCCACCAA TAATCTTTTT 3948 TATTGTTAAT AACTGGGCCG GTCTGATCTC CAAATCTTAT ACTCTGGTAG AATATGAAAC 4008 AGGGTTAAAA CTAGGTAATA GACTGGATGT CTTCGACTCC GGAGGCAGAA ACG ATG 4064 Met 1 GAA TGT GGC ATT TCT TCG TCG AAA GTA CAC GAC TCT AAA ACT AAT ACT 4112 Glu Cys Gly He Ser Ser Ser Lys Val His Asp Ser Lys Thr Asn Thr 5 10 15 ACC TAC GGA ATT ATA CAT AAC AGC ATC AAT GGT ACG GAT ACG ACG TTG 4160 Thr Tyr Gly He He His Asn Ser He Asn Gly Thr Asp Thr Thr Leu 20 25 30 TTT GAT ACT TTT CCC GAC AGT ACC GAT AAC GCG GAA GTG ACG GGG GAT 4208 Phe Asp Thr Phe Pro Asp Ser Thr Asp Asn Ala Glu Val Thr Gly Asp 35 40 45 GTG GAC GAT GTG AAG ACT GAG AGC TCT CCC GAG TCC CAA TCT GAA GAT 4256 Val Asp Asp Val Lys Thr Glu Ser Ser Pro Glu Ser Gin Ser Glu Asp 50 55 60 65 TTG TCA CCT TTT GGG AAC GAT GGA AAT GAA TCC CCC GAA ACG GTG ACG 4304 Leu Ser Pro Phe Gly Asn Asp Gly Asn Glu Ser Pro Glu Thr Val Thr 70 75 80 GAC ATT GAT GCA GTT TCA GCT GTG CGA ATG CAG TAT AAC ATT GTT TCA 4352 Asp He Asp Ala Val Ser Ala Val Arg Met Gin Tyr Asn He Val Ser 85 90 95 TCG TTA CCG CCC GGA TCT GAA GGG TAT ATC TAT GTT TGT ACA AAG CGT 4400 Ser Leu Pro Pro Gly Ser Glu Gly Tyr He Tyr Val Cys Thr Lys Arg 100 105 110 GGG GAT AAT ACC AAG AGA AAA GTC ATT GTG AAA GCT GTG ACT GGT GGC 4448 Gly Asp Asn Thr Lys Arg Lys Val He Val Lys Ala Val Thr Gly Gly 115 120 125 AAA ACC CTT GGG AGT GAA ATT GAT ATA TTA AAA AAA ATG TCT CAC CGC 4496 Lys Thr Leu Gly Ser Glu He Asp He Leu Lys Lys Met Ser His Arg 130 135 140 145 TCC ATA ATT AGA TTA GTT CAT GCT TAT AGA TGG AAA TCG ACA GTT TGT 4544 Ser He He Arg Leu Val His Ala Tyr Arg Trp Lys Ser Thr Val Cys 150 155 160 ATG GTA ATG CCT AAA TAC AAA TGC GAC TTG TTT ACG TAC ATA GAT ATC 4592 Met Val Met Pro Lys Tyr Lys Cys Asp Leu Phe Thr Tyr He Asp He 165 170 175 ATG GGA CCA TTG CCA CTA AAT CAA ATA ATT ACG ATA GAA CGG GGT TTG 4640 Met Gly Pro Leu Pro Leu Asn Gin He He Thr He Glu Arg Gly Leu 180 185 190 CTT GGA GCA TTG GCA TAT ATC CAC GAA AAG GGT ATA ATA CAT CGT GAT 4688 Leu Gly Ala Leu Ala Tyr He His Glu Lys Gly He He His Arg Asp 195 200 205 GTA AAA ACT GAA AAT ATA TTT TTG GAT AAA CCT GAA AAT GTA GTA TTG 4736 Val Lys Thr Glu Asn He Phe Leu Asp Lys Pro Glu Asn Val Val Leu 210 215 220 225 GGG GAC TTT GGG GCA GCA TGT AAA TTA GAT GAA CAT ACA GAT AAA CCC 4784 Gly Asp Phe Gly Ala Ala Cys Lys Leu Asp Glu His Thr Asp Lys Pro 230 235 240 AAA TGT TAT GGA TGG AGT GGA ACT CTG GAA ACC AAT TCG CCT GAA CTG 4832 Lys Cys Tyr Gly Trp Ser Gly Thr Leu Glu Thr Asn Ser Pro Glu Leu 245 250 255 CTT GCA CTT GAT CCA TAC TGT ACA AAA ACT GAT ATA TGG AGT GCA GGA 4880 Leu Ala Leu Asp Pro Tyr Cys Thr Lys Thr Asp He Trp Ser Ala Gly 260 265 270 TTA GTT CTG TTT GAG ATG TCA GTA AAA AAT ATA ACC TTT TTT GGC AAA 4928 Leu Val Leu Phe Glu Met Ser Val Lys Asn He Thr Phe Phe Gly Lys 275 280 285 CAA GTA AAC GGC TCA GGT TCT CAG CTG AGA TCC ATA ATT AGA TGC CTG 4976 Gin Val Asn Gly Ser Gly Ser Gin Leu Arg Ser He He Arg Cys Leu 290 295 300 305 CAA GTC CAT CCG TTG GAA TTT CCA CAG AAC AAT TCT ACA AAC TTA TGC 5024 Gin Val His Pro Leu Glu Phe Pro Gin Asn Asn Ser Thr Asn Leu Cys 310 315 320 AAA CAC TTC AAG CAG TAC GCG ATT CAG TTA CGA CAT CCA TAT GCA ATC 5072 Lys His Phe Lys Gin Tyr Ala He Gin Leu Arg His Pro Tyr Ala He 325 . 330 335 CCT CAG ATT ATA CGA AAG AGT GGT ATG ACG ATG GAT CTT GAA TAT GCT 5120 Pro Gin He He Arg Lys Ser Gly Met Thr Met Asp Leu Glu Tyr Ala 340 345 350 ATT GCA AAA ATG CTC ACA TTC GAT CAG GAG TTT AGA CCA TCT GCC CAA 5168 He Ala Lys Met Leu Thr Phe Asp Gin Glu Phe Arg Pro Ser Ala Gin 355 360 365 GAT ATT TTA ATG TTG CCT CTT TTT ACT AAA GAA CCC GCT GAC GCA TTA 5216 Asp He Leu Met Leu Pro Leu Phe T'r Lys Glu Pro Ala Asp Ala Leu 370 375 380 385 TAC ACG ATA ACT GCC GCT CAT ATG TAA ACACCCGTCA AAAATAACTT 5263 Tyr Thr He Thr Ala Ala His Met End 390 CAATGATTCA TTTTATAATA TATACTACGC GTTACCTGCA ATAATGACAA CATTCGAAGT 5323 CTTTGAAGAT TCGCAGACCT TTTTTGCGA ATG GCA CCT TCG GGA CCT ACG CCA 5376 Met Ala Pro Ser Gly Pro Thr Pro 1 5 TAT TCC CAC AGA CCG CAA ATA AAG CAT TAT GGA ACA TTT TCG GAT TGC 5424 Tyr Ser His Arg Pro Gin He Lys His Tyr Gly Thr Phe Ser Asp Cys 10 15 20 ATG AGA TAT ACT CTA A * . GAT GAG AGT AAG 3TA GAT GAT AGA TGT TCA 5472 Met Arg Tyr Thr Leu Asn Asp Glu Ser Lys Val Asp Asp Arg Cys Ser 25 30 35 40 GAC ATA CAT AAC TCC TTA GCA CAA TCC AAT GTT ACT TCA AGC ATG TCT 5520 Asp He His Asn Ser Leu Ala Gin Ser Asn Val Thr Ser Ser Met Ser 45 50 55 GTA ATG AAC GAT TCG GAA GAA TGT CCA TTA ATA AAT GGA CCT TCG ATG 5568 Val Met Asn Asp Ser Glu Glu Cys Pro Leu He Asn Gly Pro Ser Met 60 65 70 CAG GCA GAG GAC CCT A-A AGT GTT TTT TAT AAA GTT CGT AAG CCT GAC 5616 Gin Ala Glu Asp Pro LJS Ser Val Phe Tyr Lys Val Arg Lys Pro Asp 75 80 85 CGA AGT CGT GAT TTT TCA TGG CAA AAT CTG AAC TCC CAT GGC AAT AGT 5664 Arg Ser Arg Asp Phe Ser Trp Gin Asn Leu Asn Ser His Gly Asn Ser 90 95 100 GGT CTA CGT CGT GAA AAA TAT ATA CGT TCC TCT AAG AGG CGA TGG AAG 5712 Gly Leu Arg Arg Glu Lys Tyr I " - Arg Ser Ser Lys Arg Arg Trp Lys 105 110 115 120 AAT CCC GAG ATA TTT AAG GTA TCT TTG AAA TGT GAA TCA ATT GGC GCT 5760 Asn Pro Glu He Phe Lys Val Ser Leu Lys Cys Glu Ser He Gly Ala 125 130 135 GGT AAC GGA ATA AAA ATT TCA TTC TCA TTT TTC TAA CATTATAATA 5806 Gly Asn Gly He Lys He .Ser Phe Ser Phe Phe End 140 145 TATCAGATCG TTTCTTATAT ACTTATTTTC ATCGTCGGGA TATGACTAAC GTATACTAAG 5866 TTACAAGAAA CAACTGCTTA ACGTCGAACA TAACGGAAAT AAAAATATAT ATAGCGTCTC 5926 CTATAACTGT TATATTGGCA CCTTTTAGAG CTTCGGT ATG AAT AGA TAC AGA TAT 5981 Met Asn Arg Tyr Arg Tyr -30 -25 GAA AGT ATT TTT TTT AGA TAT ATC TCA TCC ACG AGA ATG ATT CTT ATA 6029 Glu Ser He Phe Phe Arg Tyr He Ser Ser Thr Arg Met He Leu He -20 -15 -10 ATC TGT TTA CTT TTG GGA ACT GGG GAC ATG TCC GCA ATG GGA CTT AAG 6077 He Cys Leu Leu Leu Gly Thr Gly Asp Met Ser Ala Met Gly Leu Lys -5 1 5 AAA GAC AAT TCT CCG ATC ATT CCC ACA TTA CAT CCG AAA GGT AAT GAA 6125 Lys Asp Asn Ser Pro He He Pro Thr Leu His Pro Lys Gly Asn Glu 10 15 20 AAC CTC CGG GCT ACT CTC AAT GAA TAC AAA ATC CCG TCT CCA CTG TTT 6173 Asn Leu Arg Ala Thr Leu Asn Glu Tyr Lys He Pro Ser Pro Leu Phe 25 30 35 40 GAT ACA CTT GAC AAT TCA TAT GAG ACA AAA CAC GTA ATA TAT ACG GAT 6221 Asp Thr Leu Asp Asn Ser Tyr Glu Thr Lys His Val He Tyr Thr Asp 45 50 55 AAT TGT AGT TTT GCT GTT TTG AAT CCA TTT GGC GAT CCG AAA TAT ACG 6269 Asn Cys Ser Phe Ala Val Leu Asn Pro Phe Gly Asp Pro Lys Tyr Thr 60 65 70 CTT CTC AGT TTA CTG TTG ATG GGA CGA CGC AAA TAT GAT GCT CTA GTA 6317 Leu Leu Ser Leu Leu Leu Met Gly Arg Arg Lys Tyr Asp Ala Leu Val 75 80 85 GCA TGG TTT GTC TTG GGC AGA GCA TGT GGG AGA CCA ATT TAT TTA CGT 6365 Ala Trp Phe Val Leu Gly Arg Ala Cys Gly Arg Pro He Tyr Leu Arg 90 95 100 GAA TAT GCC AAC TGC TCT ACT AAT GAA CCA TTT GGA ACT TGT AAA TTA 6413 Glu Tyr Ala Asn Cys Ser Thr Asn Glu Pro Phe Gly Thr Cys Lys Leu 105 110 115 120 AAG TCC CTA GGA TGG TGG GAT AGA AGA TAT GCA ATG ACG AGT TAT ATC 6461 Lys Ser Leu Gly Trp Trp Asp Arg Arg Tyr Ala Met Thr Ser Tyr He 125 130 135 GAT CGA GAT GAA TTG AAA TTG ATT ATT GCA GCA CCC AGT CGT GAG CTA 6509 Asp Arg Asp Glu Leu Lys Leu He He Ala Ala Pro Ser Arg Glu Leu 140 145 150 AGT GGA TTA TAT ACG CGT TTA ATA ATT ATT AAT GGA GAA CCC ATT TCG 6557 Ser Gly Leu Tyr Thr Arg Leu He He He Asn Gly Glu Pro He Ser 155 • 160 165 AGT GAC ATA TTA CTG ACT GTT AAA GGA ACA TGT AGT TTT TCG AGA CGG 6605 Ser Asp He Leu Leu Thr Val Lys Gly Thr Cys Ser Phe Ser Arg Arg 170 175 180 GGG ATA AAG GAT AAC AAA CTA TGC AAA CCG TTC AGT TTT TTT GTC AAT 6653 Gly He Lys Asp Asn Lys Leu Cys Lys Pro Phe Ser Phe Phe Val Asn 185 190 195 200 GGT ACA ACA CGG CTG TTA GAC ATG GTG CGA ACA GGA ACC CCG AGA GCC 6701 Gly Thr Thr Arg Leu Leu Asp Met Val Arg Thr Gly Thr Pro Arg Ala 205 210 215 CAT GAA GAA AAT GTG AAG CAG TGG CTT GAA CGA AAT GGT GGT AAA CAT 6749 His Glu Glu Asn Val Lys Gin Trp Leu Glu Arg Asn Gly Gly Lys His 220 225 230 CTA CCA ATC GTC GTC GAA ACA TCT ATG CAA CAA GTC TCA AAT TTG CCG 6797 Leu Pro He Val Val Glu Thr Ser Met Gin Gin Val Ser Asn Leu Pro 235 240 245 AGA AGT TTT AGA GAT TCA TAT TTA AAA TCA CCT GAC GAC GAT AAA TAT 6845 Arg Ser Phe Arg Asp Ser Tyr Leu Lys Ser Pro Asp Asp Asp Lys Tyr 250 255 260 AAT GAC GTC AAA ATG ACA TCG GCC ACT ACT AAT AAC ATT ACC ACC TCC 6893 Asn Asp Val Lys Met Thr Ser Ala Thr Thr Asn Asn He Thr Thr Ser 265 270 275 280 GTG GAT GGT TAC ACT GGA CTC ACT AAT CGG CCC GAG GAC TTT GAG AAA 6941 Val Asp Gly Tyr Thr Gly Leu Thr Asn Arg Pro Glu Asp Phe Glu Lys 285 290 295 GCA CCA TAC ATA ACT AAA CGA CCG ATA ATC TCT GTC GAG GAG GCA TCC 6989 Ala Pro Tyr He Thr Lys Arg Pro He He Ser Val Glu Glu Ala Ser 300 305 310 AGT CAA TCA CCT AAA ATA TCA ACA GAA AAA AAA TCC CGA ACG CAA ATA 7037 Ser Gin Ser Pro Lys He Ser Thr Glu Lys Lys Ser Arg Thr Gin He 315 320 325 ATA ATT TCA CTA GTT GTT CTA TGC GTC ATG TTT TGT TTC ATT GTA ATC 7085 He He Ser Leu Val Val Leu Cys Val Met Phe Cys Phe He Val He 330 335 340 GGG TCT GGT ATA TGG ATC CTT CGC AAA CAC CGC AAA ACG GTG ATG TAT 7133 Gly Ser Gly He Trp He Leu Arg Lys His Arg Lys Thr Val Met Tyr 345 350 355 360 GAT AGA CGT CGT CCA TCA AGA CGG GCA TAT TCC CGC CTA TAA 7175 Asp Arg Arg Arg Pro Ser Arg Arg Ala Tyr Ser Arg Leu End 365 370 CACGTGTTTG GTATGGGCGT GTCGCTATAG TGCATAAGAA GTTGACTACA TTGATCAATG 7235 ACATTATATA GCTTCTTTGG TCAGATAGAC GGCGTGTGTG ATTGCG ATG TAT GTA 7290 Met Tyr Val CTA CAA TTA TTA TTT TGG ATC CGC CTC TTT CGA GG-. _TC TGG TCT ATA 7338 Leu Gin Leu Leu Phe Trp He Arg Leu Phe Arg Gly He Trp Ser He -15 -10 -5 1 GTT TAT ACT GGA ACA TCT GTT ACG TTA TCA ACG GAC CAA TCT GCT CTT 7386 Val Tyr Thr Gly Thr Ser Val Thr Leu Ser Thr Asp Gin Ser Ala Leu 5 10 15 GTT GCG TTC CGC GGA TTA GAT AAA ATG GTG AAT GTA CGC GGC CAA CTT 7434 Val Ala Phe Arg Gly Leu Asp Lys Met Val Asn Val Arg Gly Gin Leu 20 25 30 TTA TTC CTG GGC GAC CAG ACT CGG ACC AGT TCT TAT ACA GGA ACG ACG 7482 ' Leu Phe Leu Gly Asp Gin Thr Arg Thr Ser Ser Tyr Thr Gly Thr Thr 35 40 45 GAA ATC TTG AAA TGG GAT GAA GAA TAT AAA TGC TAT TCC GTT CTA CAT 7530 Glu He Leu Lys Trp Asp Glu Glu Tyr Lys Cys Tyr Ser Val Leu His 50 55 60 65 GCG ACA TCA TAT ATG GAT TGT CCT GCT ATA GAC GCC ACG GTA TTC AGA 7578 Ala Thr Ser Tyr Met Asp Cys Pro Ala He Asp Ala Thr Val Phe Arg 70 75 80 GGC TGT AGA GAC GCT GTG GTA TAT GCT CAA CCT CAT GGT AGA GTA CAA 7626 Gly Cys Arg Asp Ala Val Val Tyr Ala Gin Pro His Gly Arg Val Gin 85 90 95 CCT TTT CCC GAA AAG GGA ACA TTG TTG AGA ATT GTC GAA CCC AGA GTA 7674 Pro Phe Pro Glu Lys Gly Thr Leu Leu Arg He Val Glu Pro Arg Val 100 105 110 TCA GAT ACA GGC AGC TAT TAC ATA CGT GTA TCT CTC GCT GGA AGA AAT 7722 Ser Asp Thr Gly Ser Tyr Tyr He Arg Val Ser Leu Ala Gly Arg Asn 115 120 125 ATG AGC GAT ATA TTT AGA ATG GTT GTT ATT ATA AGG AGT AGC AAA TCT 7770 Met Ser Asp He Phe Arg Met Val Val He He Arg Ser Ser Lys Ser 130 135 140 145 TGG GCC TGT AAT CAC TCT GCT AGT TCA TTT CAG GCC CAT AAA TGT ATT 7818 Trp Ala Cys Asn His Ser Ala Ser Ser Phe Gin Ala His Lys Cys He 150 155 160 CGC TAT GTC GAC CGT ATG GCC TTT GAA AAT TAT CTG ATT GGA CAT GTA 7866 Arg Tyr Val Asp Arg Met Ala Phe Glu Asn Tyr Leu He Gly His Val 165 170 175 GGC.AAT TTG CTG GAC AGT GAC TCG GAA TTG CAT GCA ATT TAT AAT ATT 7914 Gly Asn Leu Leu Asp Ser Asp Ser Glu Leu His Ala He Tyr Asn He 180 185 190 ACT CCC CAA TCC .ATT TCC ACA GAT ATT AAT ATT GTA ACG ACT CCA TTT 7962 Thr Pro Gin Ser He Ser Thr Asp He Asn He Val Thr Thr Pro Phe 195 200 205 TAC GAT AAT TCG GGA ACA ATT TAT TCA CCT ACG GTT TTT AAT TTG TTT 8010 Tyr Asp Asn Ser Gly Thr He Tyr Ser Pro Thr Val Phe Asn Leu Phe 210 215 220 225 AAT AAC AAT TCC CAT GTC GAT GCA ATG AAT TCG ACT GGT ATG TGG AAT 8058 Asn Asn Asn Ser H - Val Asp Ala Met Asn Ser Thr Gly Met Trp Asn 2->ϋ 235 240 ACC GTT TTA AAA TAT ACC CTT CCA AGG CTT ATT TAC TTT TCT ACG ATG 8106 Thr Val Leu Lys Tyr Thr Leu Pro Arg Leu He Tyr Phe Ser Thr Met 245 250 255 ATT GTA CTA TGT ATA ATA GCA TTG GCA ATT TAT TTG GTC TGT GAA AGG 8154 He Val Leu Cys He He Ala Leu Ala He Tyr Leu Val Cys Glu Arg 260 265 270 TGC CGC TCT CCC CAT CGT AGG ATA TAC ATC GGT GAA CCA AGA TCT GAT 82 Cys Arg Ser Pro His Arg Arg He Tyr He Gly Glu Pro Arg Ser Asp 275 280 285 GAG GCC CCA CTC ATC ACT TCT GCA GTT AAC GAA TCA TTT CAA TAT GAT 8250 Glu Ala Pro Leu He Thr Ser Ala Val Asn Glu Ser Phe Gin Tyr Asp 290 295 300 305 TAT AAT GTA AAG GAA ACT CCT TCA GAT GTT ATT GAA AAG GAG TTG ATG 8298 Tyr Asn Val Lys Glu Thr Pro Ser Asp Val He Glu Lys Glu Leu Met 310 315 320 GAA AAA CTG AAG AAG AAA GTC GAA TTG TTG GAA AGA GAA GAA TGT GTA 8346 Glu Lys Leu Lys Lys Lys Val Glu Leu Leu Glu Arg Glu Glu Cys Val 325 330 335 TAG GTTTGAGAAA CTATTATAGG TAGGTGGTAC CTGTTAGCTT AGTATAAGGG 8399 End GAGGAGCCGT TTCTTGTTTT AAAGACACGA ACACAAGGCC GTAAGTTTTA TATGTGAATT 8459 TTGTGCATGT CTGCGAGTCA GCGTCATA ATG TGT GTT TTC CAA ATC CTG ATA 8511 Met Cys Val Phe Gin He Leu He -15 ATA GTG ACG ACG ATC AAA GTA GCT GGA ACG GCC AAC ATA AAT CAT ATA 8559 He Val Thr Thr He Lys Val Ala Gly Thr Ala Asn He Asn His He -10 -5 1 5 GAC GTT CCT GCA GGA CAT TCT GCT ACA ACG ACG ATC CCG CGA TAT CCA 8607 Asp Val Pro Ala Gly His Ser Ala Thr Thr Thr He Pro Arg Tyr Pro 10 15 20 CCA GTT GTC GAT GGG ACC IT TAC ACC GAG ACG TGG ACA TGG ATT CCC 8655 Pro Val Val Asp Gly Thr Leu Tyr Thr Glu Thr Trp Thr Trp He Pro 25 30 35 AAT CAC TGC AAC GAA ACG GCA ACA GGC TAT GTA TGT CTG GAA AGT GCT 8703 Asn His Cys Asn Glu Thr Ala Thr Gly Tyr Val Cys Leu Glu Ser Ala 40 » 45 50 CAC TGT TTT ACC " .AT TTG ATA TTA GGA GTA TCC TGC ATG AGG TAT GCG 8751 His Cys Phe Thr Asp Leu He Leu Gly Val Ser Cys Met Arg Tyr Ala 55 60 65 70 GAT GAA ATC GTC TTA CGA ACT GAT AAA TTT ATT GTC GAT GCG GGA TCC 8799 Asp Glu He Val Leu Arg Thr Asp Lys Phe He Val Asp Ala Gly Ser 75 80 85 ATT AAA CAA ATA GAA TCG CTA AGT CTG AAT GGA GTT CCG AAT ATA TTC 8847 He Lys Gin He Glu Ser Leu Ser Leu Asn Gly Val Pro Asn He Phe 90 95 100 CTA TCT ACG AAA GCA AGT AAC AAG TTG GAG ATA CTA AAT GCT AGC CTA 8895 Leu Ser Thr Lys Ala Ser Asn Lys Leu Glu He Leu Asn Ala Ser Leu 105 110 115 CAA AAT GCG GGT ATC TAC ATT CGG TAT TCT AGA AAT GGG ACG AGG ACT 8943 Gin Asn Ala Gly He Tyr He Arg Tyr Ser Arg Asn Gly Thr Arg Thr 120 125 130 GCA AAG CTG GAT GTT GTT GTG GTT GGC GTT TTG GGT CAA GCA AGG GAT 8991 Ala Lys Leu Asp Val Val Val Val Gly Val Leu Gly Gin Ala Arg Asp 135 140 145 150 CGC CTA CCC CAA ATG TCC AGT CCT ATG ATC TCA TCC CAC GCC GAT ATC 9039 Arg Leu Pro Gin Met Ser Ser Pro Met He Ser Ser His Ala Asp He 155 160 165 AAG TTG TCA TTA AAA AAC TTT AAA GCA TTA GTA TAT CAC GTG GGA GAT 9087 Lys Leu Ser Leu Lys Asn Phe Lys Ala Leu Val Tyr His Val Gly Asp 170 175 180 ACT ATC AAT GTC TCG ACG GCG GTT ATA CTA GGA CCT TCT CCG GAG ATA 9135 Thr He Asn Val Ser Thr Ala Val He Leu Gly Pro Ser Pro Glu He 185 190 195 TTC ACA TTG GAA TTT AGG GTG TTG TTC CTC CGT TAT AAT CCA ACG TGC 9183 Phe Thr Leu Glu Phe Arg Val Leu Phe Leu Arg Tyr Asn Pro Thr Cys 200 205 210 AAG TTC GTC ACG ATT TAT GAA CCT TGT ATA TTT CAC CCC AAA GAA CCA 9231 Lys Phe Val Thr He Tyr Glu Pro Cys He Phe His Pro Lys Glu Pro 215 220 225 230 GAG TGT ATT ACT ACT GCA GAA CAA TCG GTA TGT CAT TTC GCA TCC AAC 9279 Glu Cys He Thr Thr Ala Glu Gin Ser Val Cys His Phe Ala Ser Asn 235 240 245 ATT GAC ATT CTG CAG ATA GCC GCC GCA CGT TCT GAA AAT TGT AGC ACA 9327 He Asp He Leu Gin He Ala Ala Ala Arg Ser Glu Asn Cys Ser Thr 250 255 260 GGG TAT CGT AGA TGT ATT TAT GAC ACG GCT ATC GAT GAA TCT GTG CAG 9375 Gly Tyr Arg Arg Cys He Tyr Asp Thr Ala He Asp Glu Ser Val Gin 265 270 275 GCC AGA TTA ACA TTC ATA GAA CCA GGA ATT CCT TCC TTT AAA ATG AAA 9423 Ala Arg Leu Thr Phe He Glu Pro Gly He Pro Ser Phe Lys Met Lys 280 285 290 GAT GTC CAG GTA GAC GAT GCT GGA TTG TAT GTG GTT GTG GCT TTA TAC 9471 Asp Val Gin Val Asp Asp Ala Gly Leu Tyr Val Val Val Ala Leu Tyr 295 300 305 310 AAT GGA CGT CCA AGT GCA TGG ACT TAC ATT TAT TTG TCA ACG GTG GAA 9519 Asn Gly Arg Pro Ser Ala Trp Thr Tyr He Tyr Leu Ser Thr Val Glu 315 320 325 ACA TAT CTT AAT GTA TAT GAA AAC TAC CAC AAG CCG GGA TTT GGG TAT 9567 Thr Tyr Leu Asn Val Tyr Glu Asn Tyr His Lys Pro Gly Phe Gly Tyr 330 335 340 AAA TCA TTT CTA CAG AAC AGT AGT ATC GTC GAC GAA AAT GAG GCT AGC 9615 Lys Ser Phe Leu Gin Asn Ser Ser He Val Asp Glu Asn Glu Ala Ser 345 350 355 GAT TGG TCC AGC TCG TCC ATT AAA CGG AGA AAT AAT GGT ACT ATC ATT 9663 Asp Trp Ser Ser Ser Ser He Lys Arg Arg Asn Asn Gly Thr He He 360 365 370 TAT GAT ATT TTA CTC ACA TCG CTA TCA ATT GGG GCG ATT ATT ATC GTC 9711 Tyr Asp He Leu Leu Thr Ser Leu Ser He Gly Ala He He He Val 375 380 385 390 ATA GTA GGG GGT GTT TGT ATT GCC ATA TTA ATT AGG CGT AGG AGA CGA 9759 He Val Gly Gly Val Cys He Ala He Leu He Arg Arg Arg Arg Arg 395 410 415 CGT CGC ACG AGG GGG TTA TTC GAT GAA TAT CCC AAA TAT ATG ACG CTA 9807 Arg Arg Thr Arg Gly Leu Phe Asp Glu Tyr Pro Lys Tyr Met Thr Leu 420 425 430 CCA GGA AAC GAT CTG GGG GGC ATG AAT GTA CCG TAT GAT AAT ACA TGC 9855 Pro Gly Asn Asp Leu Gly Gly Met Asn Val Pro Tyr Asp Asn Thr Cys 435 440 445 TCT GGT AAC CAA GTT GAA TAT TAT CAA GAA AAG TCG GCT AAA ATG AAA 9903 Ser Gly Asn Gin Val Glu Tyr Tyr Gin Glu Lys Ser Ala Lys Met Lys 450 455 460 AGA ATG GGT TCG GGT TAT ACC GCT TGG CTA AAA AAT GAT ATG CCG AAA 9951 Arg Met Gly Ser Gly Tyr Thr Ala Trp Leu Lys Asn Asp Met Pro Lys 465 470 475 480 ATT AGG AAA CGC TTA GAT TTA TAC CAC TGA TATGTACATA TTTAAACTTA 10001 He Arg Lys Arg Leu Asp Leu Tyr His End 485 ATGGGATATA GTATATGGAC GTCTATATGA CGAGAGTAAA TAAACTGACA ATGCAAATGA 10061 AGCTGATCTA TATTGTGCTT TATATTGGGA CAAACCACTC GCACAAGCTC ATTCAACACA 10121 TCCACTCTTG CTATTAAATT CCCCATTATA TAACAATACT GACATAACAC TCATATTAAG 10181 GGGAGAAAAT AAATATGCAT GGCCGATCAT ATTTTATTGA GATCCGAAAA TATATCATGC 10241 AAATAAGCAT GTTCTAGCAC CACTGCAACA TGTGGTTTAT CGATTTCCGG AAAGAATAGT 10301 TGAACCATTG CCTCCGAGCA GTTGGCGATC CGTTGACCTG CAGGTCGAC 10350 (3) Information for SEQ ID NO: 2 (i) Sequence Characteristics : (A) Length: 10,350 base pairs (B) Type: nucleic acid (C) Strandedness: double (D) Topology: linear (ii) Molecule Type: (A) Description: genomic DNA (iii) HYPOTHETICAL: Yes (iv) ANTI-SENSE: Yes (vi) ORIGINAL SOURCE: (A) Organism: MDV, GA strain (vii) IMMEDIATE SOURCE: (A) Library: genomic (xi) SEQUENCE DESCRIPTION: SEQ ID NO : 2 : GTCGACCTGC AGGTCAACGG ATCGCCAACT GCTCGGAGGC AATGGTTCAA CTATTCTTTC 60 CGGAAATCGA TAAACCACAT GTTGCAGTGG TGCTAGAACA TGCTTATTTG CATGATATAT 120 TTTCGGATCT CAATAAAATA TGATCGGCCA TGCATATTTA TTTTCTCCCC TTAATATGAG 180 TGTTATGTCA GTATTGTTAT ATAATGGGGA ATTTAATAGC AAGAGTGGAT GTGTTGAATG 240 AGCTTGTGCG AGTGGTTTGT CCCAATATAA AGCACAATAT AGATCAGCTT CATTTGCATT 300 GTCAGTTTAT TTACTCTCGT CATATAGACG TCCATATACT ATATCCCATT AAGTTTAAAT 360 ATGTACATAT CAGTGGTATA AATCTAAGCG TTTCCTAATT TTCGGCATAT CATTTTTTAG 420 CCAAGCGGTA TAACCCGAAC CCATTCTTTT CATTTTAGCC GACTTTTCTT GATAATATTC 480 AACTTGGTTA CCAGAGCATG TATTATCATA CGGTACATTC ATGCCCCCCA GATCGTTTCC 540 TGGTAGCGTC ATATATTTGG GATATTCATC GAATAACCCC CTCGTGCGAC GTCGTCTCCT 600 ACGCCTAATT AATATGGCAA TACAAACACC CCCTACTATG ACGATAATAA TCGCCCCAAT 660 TGATAGCGAT GTGAGTAAAA TATCATAAAT GATAGTACCA TTATTTCTCC GTTTAATGGA 720 CGAGCTGGAC CAATCGCTAG CCTCATTTTC GTCGACGATA CTACTGTTCT GTAGAAATGA 780 TTTATACCCA AATCCCGGCT TGTGGTAGTT TTCATATACA TTAAGATATG TTTCCACCGT 840 TGACAAATAA ATGTAAGTCC ATGCACTTGG ACGTCCATTG TATAAAGCCA CAACCACATA 900 CAATCCAGCA TCGTCTACCT GGACATCTTT CATTTTAAAG GAAGGAATTC CTGGTTCTAT 960 GAATGTTAAT CTGGCCTGCA CAGATTCATC GATAGCCGTG TCATAAATAC ATCTACGATA 1020 CCCTGTGCTA CAATTTTCAG AACGTGCGGC GGCTATCTGC AGAATGTCAA TGTTGGATGC 1080 GAAATGACAT ACCGATTGTT CTGCAGTAGT AATACACTCT GGTTCTTTGG GGTGAAATAT 1140 ACAAGGTTCA TAAATCGTGA CGAACTTGCA CGTTGGATTA TAACGGAGGA ACAACACCCT 1200 AAATTCCAAT GTGAATATCT CCGGAGAAGG TCCTAGTATA ACCGCCGTCG AGACATTGAT 1260 AGTATCTCCC ACGTGATATA CTAATGCTTT AAAGTTTTTT AATGACAACT TGATATCGGC 1320 GTGGGATGAG ATCATAGGAC TGGACATTTG GGGTAGGCGA TCCCTTGCTT GACCCAAAAC 1380 GCCAACCACA ACAACATCCA GCTTTGCAGT CCTCGTCCCA TTTCTAGAAT ACCGAATGTA 1440 GATACCCGCA TTTTGTAGGC TAGCATTTAG TATCTCCAAC TTGTTACTTG CTTTCGTAGA 1500 TAGGAATATA TTCGGAACTC CATTCAGACT TAGCGATTCT ATTTGTTTAA TGGATCCCGC 1560 ATCGACAATA AATTTATCAG TTC.GTAAGAC GATTTCATCC GCATACCTCA TGCAGGATAC 1620 TCCTAATATC AAATCGGTAA AACAGTGAGC ACTTTCCAGA CATACATAGC CTGTTGCCGT 1680 TTCGTTGCAG TGATTGGGAA TCCATGTCCA CGTCTCGGTG TAAAGGGTCC CATCGACAAC 1740 TGGTGGATAT CGCGGGATCG TCGTTGTAGC AGAATGTCCT GCAGGAACGT CTATATGATT 1800 TATGTTGGCC GTTCCAGCTA CTTTGATCGT CGTCACTATT ATCAGGATTT GGAAAACACA 1860 CATTATGACG CTGACTCGCA GACATGCACA AAATTCACAT ATAAAACTTA CGGCCTTGTG 1920 TTCGTGTCTT TAAAACAAGA AACGGCTCCT CCCCTTATAC TAAGCTAACA GGTACCACCT 1980 ACCTATAATA GTTTCTCAAA CCTATACACA TTCTTCTCTT TCCAACAATT CGACTTTCTT 2040 CTTCAGTTTT TCCATCAACT CCTTTTCAAT AACATCTGAA GGAGTTTCCT TTACATTATA 2100 ATCATATTGA AATGATTCGT TAACTGCAGA AGTGATGAGT GGGGCCTCAT CAGATCTTGG 2160 TTCACCGATG TATATCCTAC GATGGGGAGA GCGGCACCTT TCACAGACCA AATAAATTGC 2220 CAATGCTATT ATACATAGTA CAATCATCGT AGAAAAGTAA ATAAGCCTTG GAAGGGTATA 2280 TTTTAAAACG GTATTCCACA TACCAGTCGA ATTCATTGCA TCGACATGGG AATTGTTATT 2340 AAACAAATTA AAAACCGTAG GTGAATAAAT TGTTCCCGAA TTATCGTAAA ATGGAGTCGT 2400 TACAATATTA ATATCTGTGG AAATGGATTG GGGAGTAATA TTATAAATTG CATGCAATTC 2460 CGAGTCACTG TCCAGCAAAT TGCCTACATG TCCAATCAGA TAATTTTCAA AGGCCATACG 2520 GTCGACATAG CGAATACATT TATGGGCCTG AAATGAACTA GCAGAGTGAT TACAGGCCCA 2580 AGATTTGCTA CTCCTTATAA TAACAACCAT TCTAAATATA TCGCTCATAT TTCTTCCAGC 2640 GAGAGATACA CGTATGTAAT AGCTGCCTGT ATCTGATACT CTGGGTTCGA CAATTCTCAA 2700 CAATGTTCCC TTTTCGGGAA AAGGTTGTAC TCTACCATGA GGTTGAGCAT ATACCACAGC 2760 GTCTCTACAG CCTCTGAATA CCGTGGCGTC TATAGCAGGA CAATCCATAT ATGATGTCGC 2820 ATGTAGAACG GAATAGCATT TATATTCTTC ATCCCATTTC AAGATTTCCG TCGTTCCTGT 2880 ATAAGAACTG GTCCGAGTCT GGTCGCCCAG GAATAAAAGT TGGCCGCGTA CATTCACCAT 2940 TTTATCTAAT CCGCGGAACG CAACAAGAGC AGATTGGTCC GTTGATAACG TAACAGATGT 3000 TCCAGTATAA ACTATAGACC AGATGCCTCG AAAGAGGCGG ATCCAAAATA ATAATTGTAG 3060 TACATACATC GCAATCACAC ACGCCGTCTA TCTGACCAAA GAAGCTATAT AATGTCATTG 3120 ATCAATGTAG TCAACTTCTT ATGCACTATA GCGACACGCC CATACCAAAC ACGTGTTATA 3180 GGCGGGAATA TGCCCGTCTT GATGGACGAC GTCTATCATA CATCACCGTT TTGCGGTGTT 3240 TGCGAAGGAT CCATATACCA GACCCGATTA CAATGAAACA AAACATGACG CATAGAACAA 3300 CTAGTGAAAT TATTATTTGC GTTGGGGATT TTTTTTCTGT TGATATTTTA GGTGATTGAC 3360 TGGATGCCTC CTCGACAGAG ATTATCGGTC GTTTAGTTAT GTATGGTGCT TTCTCAAAGT 3420 CCTCGGGCCG ATTAGTGAGT CCAGTGTAAC CATCCACGGA GGTGGTAATG TTATTAGTAG 3480 TGGCCGATGT CATTTTGACG TCATTATATT TATCGTCGTC AGGTGATTTT AAATATGAAT 3540 CTCTAAAACT TCTCGGCAAA TTTGAGACTT GTTGCATAGA TGTTTCGACG ACGATTGGTA 3600 GATGTTTACC ACCATTTCGT TCAAGCCACT GCTTCACATT TTCTTCATGG GCTCTCGGGG 3660 TTCCTGTTCG CACCATGTCT AACAGCCGTG TTGTACCATT GACAAAAAAA CTGAACGGTT 3720 TGCATAGTTT GTTATCCTTT ATCCCCCGTC TCGAAAAACT ACATGTTCCT TTAACAGTCA 3780 GTAATATGTC ACTCGAAATG GGTTCTCCAT TAATAATTAT TAAACGCGTA TATAATCCAC 3840 TTAGCTCACG ACTGGGTGCT GCAATAATCA ATTTCAATTC ATCTCGATCG ATATAACTCG 3900 TCATTGCATA TCTTCTATCC CACCATCCTA GGGACTTTAA TTTACAAGTT CCAAATGGTT 3960 CATTAGTAGA GCAGTTGGCA TATTCACGTA AATAAATTGG TCTCCCACAT GCTCTGCCCA 4020 AGACAAACCA TGCTACTAGA GCATCATATT TGCGTCGTCG CATCAACAGT AAACTGAGAA 4080 GCGTATATTT CGGATCGCCA AATGGATTCA AAACAGCAAA ACTACAATTA TCCGTATATA 4140 TTACGTGTTT TGTCTCATAT GAATTGTCAA GTGTATCAAA CAGTGGAGAC GGGATTTTGT 4200 ATTCATTGAG AGTAGCCCGG AGGTTTTCAT TACCTTTCGG ATGTAATGTG GGAATGATCG 4260 GAGAATTGTC TTTCTTAAGT CCCATTGCGG ACATGTCCCC AGTTCCCAAA AGTAAACAGA 4320 TTATAAGAAT CATTCTCGTG GATGAGATAT ATCTAAAAAA AATACTTTCA TATCTGTATC 4380 TATTCATACC GAAGCTCTAA AAGGTGCCAA TATAACAGTT ATAGGAGACG CTATATATAT 4440 TTTTATTTCC GTTATGTTCG ACGTTAAGCA GTTGTTTCTT GTAACTTAGT ATACGTTAGT 4500 CATATCCCGA CGATGAAAAT AAGTATATAA GAAACGATCT GATATATTAT AATGTTAGAA 4560 AAATGAGAAT GAAATTTTTA TTCCGTTACC AGCGCCAATT GATTCACATT TCAAAGATAC 4620 CTTAAATATC TCGGGATTCT TCCATCGCCT CTTAGAGGAA CGTATATATT TTTCACGACG 4680 TAGACCACTA TTGCCATGGG AGTTCAGATT TTGCCATGAA AAATCACGAC TTCGGTCAGG 4740 CTTACGAACT TTATAAAAAA CACTTTTAGG GTCCTCTGCC TGCATCGAAG GTCCATTTAT 4800 TAATGGACAT TCTTCCGAAT CGTTCATTAC AGACATGCTT GAAGTAACAT TGGATTGTGC 4860 TAAGGAGTTA TGTATGTCTG AACATCTATC ATCTACCTTA CTCTCATCGT TTAGAGTATA 4920 TCTCATGCAA TCCGAAAATG TTCCATAATG CTTTATTTGC GGTCTGTGGG AATATGGCGT 4980 AGGTCCCGAA GGTGCCATTC GCAAAAAAGG TCTGCGAATC TTCAAAGACT TCGAATGTTG 5040 TCATTATTGC AGGTAACGCG TAGTATATAT TATAAAATGA ATCATTGAAG TTATTTTTGA 5100 CGGGTGTTTA CATATGAGCG GCAGTTATCG TGTATAATGC GTCAGCGGGT TCTTTAGTAA 5160 AAAGAGGCAA CATTAAAATA TCTTGGGCAG ATGGTCTAAA CTCCTHATCG AATGTGAG" 5220 TTTTTGCAAT AGCATATTCA AGATCCATCG TCATACCACT CTTTCGTATA ATCTGAGGv... 5280 TTGCATATGG ATGTCGTAAC TGAATCGCGT ACTGCTTGAA GTGTTTGCAT AAGTTTGTAG 5340 AATTGTTCTG TGGAAATTCC AACGGATGGA CTTGCAGGCA TCTAATTATG GATCTCAGCT 5400 GAGAACCTGA GCCGTTTACT TGTTTGCCAA AAAAGGTTAT ATTTTTTACT GACATCTCAA 5460 ACAGAACTAA TCCTGCACTC CATATATCAG TTTTTGTACA GTATGGATCA AGTGCAAGCA 5520 GTTCAGGCGA ATTGGTTTCC AGAGTTCCAC TCCATCCATA ACATTTGGGT TTATCTGTAT 5580 GTTCATCTAA TTTACATGCT GCCCCAAAGT CCCCCAATAC TACATTTTCA GGTTTATCCA 5640 AAAATATATT TTCAGTTTTT ACATCACGAT GTATTATACC CTTTTCGTGG ATATATGCCA 5700 ATGCTCCAAG CAAACCCCGT TCTATCGTAA TTATTTGATT TAGTGGCAAT GGTCCCATGA 5760 TATCTATGTA CGTAAACAAG TCGCATTTGT ATTTAGGCAT TACCATACAA ACTGTCGATT 5820 TCCATCTATA AGCATGAACT AATCTAATTA TGGAGCGGTG AGACATTTTT TTTAATATAT 5880 CAATTTCACT CCCAAGGGTT TTGCCACCAG TCACAGCTTT CACAATGACT TTTCTCTTGG 5940 TATTATCCCC ACGCTTTGTA CAAACATAGA TATACCCTTC AGATCCGGGC GGTAACGATG 6000 AAACA.* GTT ATACTGCATT CGCACAGCTG AAACTGCATC AATGTCCGTC ACCGTTTCGG 6060 GGGATTCATT TCCATCGTTC CCAΛAAGGTG ACAAATCTTC AGATTGGGAC TCGGGAGAGC 6120 TCTCAGTCTT CACATCGTCC ACATCCCCCG TCACTTCCGC GTTATCGGTA CTGTCGGGAA 6180 AAGTATCAAA CAACGTCGTA TCCGTACCAT TGATGCTGTT ATGTATAATT CCGTAGGTAG 6240 TATTAGTTTT AGAGTCGTGT ACTTTCGACG AAGAAATGCC ACATTCCATC GTTTCTGCCT 6300 CCGGAGTCGA AGACATCCAG TCTATTACCT AGTTTTAACC CTGTTTCATA TTCTACCAGA 6360 GTATAAGATT 1G AGATCAG ACCGGCCCAG TTATTAACAA TAAAAAAGAT TATTGGTGGA 6420 GGTGAAG ATG GGT GTG TCC ATG ATA ACT ATA GTC ACA CTT CTA GAT GAA 6469 Met Gly Val Ser Met He Thr He Val Thr Leu Leu Asp Glu 1 5 10 TGC GAT CGA TTG CCA GGA AG TCT AGA GAT GCT GCA TCT ACT TTA TGG 6517 Cys Asp Arg Leu Pro Gly Ar :er Arg Asp Ala Ala Ser Thr Leu Trp 15 20 25 30 ATA TTC CTT ATA AAG CAA TGT ATG GAA CAA ATA CAG GAT GAT GTG GGT 6565 He Phe Leu He Lys Gin Cys Met Glu Gin He Gin Asp Asp Val Gly 35 40 45 G J CCC ATA ATC GCC AGA GCT GCA GAC CTA TTC CGT TTT GCC AAA CCC 6613 Val Pro He He Ala Arg Ala Ala Asp Leu Phe Arg Phe Ala Lys Pro 50 55 60 ATG TTA ATT CTT CCT CGG CAA CAT CGA CCG ATA GTA AGG ACA AAG CCA 6661 Met Leu He Leu Pro Arg Gin His Arg Pro He Val Arg Thr Lys Pro 65 70 75 CCA GAT GGA ACT GGA GTT CGT GGT ACC GGA TTG GCC GGA ACT AGG GAT 6709 Pro Asp Gly Thr Gly Val Arg Gly Thr Gly Leu Ala Gly Thr Arg Asp 80 85 90 TCG TTT ATA GTG CGG CTA TTT GAA GAT GTT GCA GGA TGT TCC ACA GAA 6757 Ser. Phe He Val Arg Leu Phe Glu Asp Val Ala Gly Cys Ser Thr Glu 95 100 105 110 TGG CAG GAT GTT CTA TCT GGA TAT TTG ATG TTG GAA TCT GAA GTT TCT 6805 Trp Gin Asp Val Leu Ser Gly Tyr Leu Met Leu Glu Ser Glu Val Ser 115 120 125 GGT AAT GCT CCA CAT AGC TTG TGG ATA GTT GGG GGG GCA GAT ATA TGT 6853 Gly Asn Ala Pro His Ser Leu Trp He Val Gly Ala Ala Asp He Cys 130 135 140 GCC ATT GCG CTC GAA TGT ATT CCT TTG CCA AAA AGG TTA CTT GCA ATC 6901 Ala He Ala Leu Glu Cys He Pro Leu Pro Lys Arg Leu Leu Ala He 145 150 155 AAA GTG TCT GGG ACC TGG TCC GGT ATG CCG TGG GCC ATT CCC GAC AAT 6949 Lys Val Ser Gly Thr Trp Ser Gly Met Pro Trp Ala He Pro Asp Asn 160 165 ' 170 ATT CAA ACT CTC TTG ACA TCT ACA TGG GAA CCG AAG TTC GAC ACC CCA 6997 He Gin Thr Leu Leu Thr Ser Thr Trp Glu Pro Lys Phe Asp Thr Pro 175 180 185 190 GAA GAT AGA GCG CAT TTT TGC GAC AGT GAT ATG GTA TGT GTA TAC AAA 7045 Glu Asp Arg Ala His Phe Cys Asp Ser Asp Met Val Cys Val Tyr Lys 195 200 205 ATC CTC GGG TCC CCA CCC AAT CCT CTA AAA CCT CCG GAA ATC GAA CCA 7093 He Leu Gly Ser Pro Pro Asn Pro Leu Lys Pro Pro Glu He Glu Pro 210 215 220 CCT CAA ATG AGT AGT ACA CCC GGC AGA TTA TTC TGT TGT GGA AAA TGT 7141 Pro Gin Met Ser Ser Thr Pro Gly Arg Leu Phe Cys Cys Gly Lys Cys 225 230 235 TGC AAG AAA GAA GAT AGA GAT GCG ATT GCA ATT CCG GTT CGT TAC ACT 7189 Cys Lys Lys Glu Asp Arg Asp Ala He Ala He Pro Val Arg Tyr Thr 240 245 250 GCG ACA GGA AAG TCA CGA ATA CAG AAA AAA TGT AGA GCC GGT AGT CAT 7237 Ala Thr Gly Lys Ser Arg He Gin Lys Lys Cys Arg Ala Gly Ser His 255 260 265 270 TAG CTGTTATTCG ACAGACCTAC TTGCTACCAA TTAGATATAA TTACATGATG End GGGCGTATAC ACATTACGAT TAGGTGCATC GCTACAACCG TCGCTATAGT GTCACGTATA 7350 ATTTGTATAT TAGTGCAATA ACAAACCCTT CTAGATCACT TATGTATCCA GGCTATCTTC 7410 CATATACTTC TAACATCAGG AGAGATTCAA CAATCGAGCG CATTTGAAAG ACAACG ATG 7469 Met 1 AGC AGA GTC AAT GCT ACA ATG TTC GAT GAT ATG GAT ATA CCA AGA GGA 7517 Ser Arg Val Asn Ala Thr Met Phe Asp Asp Met Asp He Pro Arg Gly 5 10 15 CGA TTT GGT AAG CCA CCG AGA AAG ATT ACT AAT GTA AAT TTT TGG CAT 7565 Arg Phe Gly Lys Pro Pro Arg Lys He Thr Asn Val Asn Phe Trp His 20 25 30 GTG GTT GTT GAT GAA TTC ACA GAA GGA ATC GTT CAA TGT ATG GAA GCC 7613 Val Val Val Asp Glu Phe Thr Glu Gly He Val Gin Cys Met Glu Ala 35 40 45 CGA GAG AGA TTA GGC CTT TTA TGT ACC ATA TCT ACT AAC GAG GGA TCT 7661 Arg Glu Arg Leu Gly Leu Leu Cys Thr He Ser Thr Asn Glu Gly Ser 50 55 60 65 ATT ACA TCG TTT GAT ATA CAC AAG GAT ATG TGG TGT CAA ATG GTT ATC 7709 He Thr Ser Phe Asp He His Lys Asp Met Trp Cys Gin Met Val He 70 75 80 TGG TCT GCC TAT AGA TTT TTT GCC ATG ATG GAC AAA ATG TTT TCG ATT 7757 Trp Ser Ala Tyr Arg Phe Phe Ala Met Met Asp Lys Met Phe Ser He 85 90 95 GAA ACT ATC ACA AAT TTT ACA GAA ACT GAT CTT ACC GAA ACT GGT CAG 7805 Glu Thr He Thr Asn Phe Thr Glu Thr Asp Leu Thr Glu Thr Gly Gin 100 105 110 TGG AGA ATA TTC TAT AGA ACT TGG GAT GTG AGA GAT GCA TTG AAG ATG 7853 Trp Arg He Phe Tyr Arg Thr Trp Asp Val Arg Asp Ala Leu Lys Met 115 120 125 AAA CAG GTG GGA CCA TTT TTG CCC GCA TTG TTT TCA TTT CAT CTG GAA 7901 Lys Gin Val Gly Pro Phe Leu Pro Ala Leu Phe Ser Phe His Leu Glu 130 135 140 145 AAC TGG ACC ACA ATG CTT TCC ATA GGA ATC AAC AAG GGT TAT GAT CGA 7949 Asn Trp Thr Thr Met Leu Ser He Gly He Asn Lys Gly Tyr Asp Arg 150 155 160 CAC AAT ACA CGA AAT ATG TTC ATG ACA ATA CAG TCT GCA AGA AAT GTC 7997 His Asn Thr Arg Asn Met Phe Met Thr He Gin Ser Ala Arg Asn Val 165 170 175 CTT AGC GGG GCA ATA GAG GTA GCT CGA TAT GCC GTG GTT CTT GCT CTA 8045 Leu Ser Gly Ala He Glu Val Ala Arg Tyr Ala Val Val Leu Ala Leu 180 185 190 CCT GTG TGC GAG TAT AGA ACA CCC TTA GGC CTG CCG GAT GAT AGC ATA 8093 Pro Val Cys Glu Tyr Arg Thr Pro Leu Gly Leu Pro Asp Asp Ser He 195 200 205 GGA AAT GCC ATC AAG ACA TGC TGC ACG CAA ATG CAA GCG AAT CGA TTG 8141 Gly Asn Ala He Lys Thr Cys Cys Thr Gin Met Gin Ala Asn Arg Leu 210 215 220 225 ACA GAA ACT GGA ATA TCC AAG GAC AGT GGA CAT AAA ATA AAT GAT TCT 8189 Thr Glu Thr Gly He Ser Lys Asp Ser Gly His Lys He Asn Asp Ser 230 235 240 TCT GAA GAG GAG TTG TAT TAT AGA ACC ATA CAT GAT CTT ATC AAA CCT 8237 " Ser Glu Glu Glu Leu Tyr Tyr Arg Thr He His Asp Leu He Lys Pro 245 250 255 AAC CGG GAA CAT TGC ATA TCA TGC AAT ATT GAG AAT AGC ATG GAT ATA 8285 Asn Arg Glu His Cys He Ser Cys Asn He Glu Asn Ser Met Asp He 260 265 270 GAT CCC ACT ATT CAC CAT CGA TCT TCT AAT GTC ATA ACT TTA CAA GGT 8333 Asp Pro Thr He His His Arg Ser Ser Asn Val He Thr Leu Gin Gly 275 280 285 ACA TCA ACA TAT CCA TTT GGA CGC AGG CCG ATG AGT CGA ATG GAT GTT 8381 Thr Ser Thr Tyr Pro Phe Gly Arg Arg Pro Met Ser Arg Met Asp Val 290 295 300 305 GGA GGT CTT ATG TAC CAG CAC CCC TAC ATT TGC CGC AAT CTC CAT TTA 8429 Gly Gly Leu Met Tyr Gin His Pro Tyr He Cys Arg Asn Leu His Leu 310 315 320 CGT CCG CCT CGA TCC AGA CTA ATG AAT AGT AAA ATC CTA CAG ACA TTT 8477 Arg Pro Pro Arg Ser Arg Leu Met Asn Ser Lys He Leu Gin Thr Phe 325 330 335 AGA CAA AGT TTC AAT CGA AGT AAT CCT CAT GCA TAC CCC ATA TAA 8522 Arg Gin Ser Phe Asn Arg Ser Asn Pro His Ala Tyr Pro He End 340 345 350 TACATACAAT CATGACAACA CTGTAATGCC TTATTGAAAA TAAAATTTTA TTATTTAAAC 8582 AACGTTAGTA GCAGTTTTTC CTAAAATCCT ATTAATAATT GTGCGATTAG TTATAAGTAG 8642 GATTCCCCGT CTCCTGTTGG CGATTCCCGA AGATTTGTCA GATAATGTGC CAATTCAGCA 8702 TCATCACCGA TTGCTGCATT CCCCTTAGTA GCGACGGCAC GACATAAAGG TTTCCAATAA 8762 GACTCTATTT CGGGGAGTGG ACTTATTCCA CAGCCCGTTG CCGAACCTAC TATGTCCATA 8822 AGACGGACAT TCTTCTCATA TAAGCGCGAA ACAGTACAGT ATCCAGCATG TCCAAGACAA 8882 CACCAATACA TCATGATAGT AAACCGAGTG TCCATTTCTT CGTGTGTAAG AGGAGCACGT 8942 TCAATACACC GTAAAGCCCG GCCTACAATT TTTCTCGTCG GGTCTGTCGG GTGGAATGGC 9002 GAAGCAGAAA TATCATATTC GTTAAGCGTG ACAGTCATTC TGTCGAATAT CTCACCCCAC 9062 AAACGAGACG ATGGTGGTTT TCCAGCTTTC ATAGCAGCCT GGGAGATCGT AATATGGTCC TGGCTAGACT GCGTACAGAT TTAGGCAATA GCGCAACATG GCAGAAAGTA TATCATAACT CTGTTCTTTT GGAGAATCTA CCCGGAGTTG CTAGATTTGC GCCGTAGAGA CCACATGGCC ATACCTCTCC AATATGTTTT GGCGCTCGTC TCCAGTATTC AAACACGTTC TCCTCTCATT AGGCTCAACG TATCTTCATA TACAACAAAA AGGCAACACG TTATTTGACA CGCCCCTTCA GGGTCAGCGT TTGTTGCAAC AGATCATGAC AAATAAATCC AAAATCTATT ATTAGATAGA TCAAAGAATG TCGGCTCTAT GTCTAACAAT TAAAATTATA TTTCTCTTCA AGTCTGGATA GTTAATGCAA TTTACTGTCT ACCGACAAAT TTTTACATCG CAGTCTGAAG AAATAGTTCC CGAGGACGCA GCGATTGGGT ATCGGAGGCA TATATATCGG ATATAGGATG GGCGCTTCGA CTATCAGCAT CCTGCGCAGA TGTAGACTTT GGCGTGGGGT CAAATTCATG ATAGTTTCCC TTTTAGTCGA TATCCCATTC GACCAATCAT ATGAATATCG AATAGTGCTC ATCGTGGAAC GGACCGCTAT TTAGTCGACA TCGAATAAAA CATCGAAATA ATCCGCACAT AACCGAGCGA CATCGGGTTT CCATGGTAGA GGACAAAATT AT fiAGTTCA AAGTCTTGAT CGGACGAGTC ACTGCCATAT TCCGGATGTG TTGATAATCT TCGTCGTCGC TCTCATTATC TGACGATGAT AATCGTGTAT TCGATCTCGA TCACGACTCA TGTTGCCTCC GATGGAGCCG AAAGCAGGTT GTGTAATTTG GAGACTTTGG CCTGTATTAT ATAGCTACCA GCTTTTATCT ACAATAATTG CTAGAATTTA CATCACGTGA TATCCGGTCA AAAATTACTT CCAGCCCCTA ATGTACTACT TGCTCTATAT ATTCTCCACA ATGGTAAACC AAGATTTCAC TCCAATTTCA AGGAATTC (4) Information for SEQ ID NO: 3 (i) Sequence Charteristics: (A) Length: 497 amino acids (B) Type: peptide (C) Strandedness: single (D) Topology: linear (ii) Molecule Type: (A) Description: polypeptide (vi) ORIGINAL SOURCE: (A) Organism: MDV, GA strain (vii) IMMEDIATE SOURCE: (A) : Librar : genomic (xi) SEQUENCE DESCRIPTION: SEQ ID NO:3: Met Cys Val Phe Gin He Leu He He Val Thr Thr He Lys Val Ala -15 -10 -5 Gly Thr Ala Asn He Asn His He Asp Val Pro Ala Gly His Ser Ala 1 5 10 Thr Thr Thr He Pro Arg Tyr Pro Pro Val Val Asp Gly Thr Leu Tyr 15 20 25 30 Thr Glu Thr Trp Thr Trp He Pro Asn His Cys Asn Glu Thr Ala Thr 35 40 45 Gly Tyr Val Cys Leu Glu Ser Ala His Cys Phe Thr Asp Leu He Leu 50 55 60 Gly Val Ser Cys Met Arg Tyr Ala Asp Glu He Val Leu Arg Thr Asp 65 70 75 Lys Phe He Val Asp Ala Gly Ser He Lys Gin He Glu Ser Leu Ser 80 85 90 Leu Asn Gly Val Pro Asn He Phe Leu Ser Thr Lys Ala Ser Asn Lys 95 100 105 110 Leu Glu He Leu Asn Ala Ser Leu Gin Asn Ala Gly He Tyr He Arg 115 120 125 Tyr Ser Arg Asn Gly Thr Arg Thr Ala Lys Leu Asp Val Val Val Val 130 135 140 Gly Val Leu Gly Gin Ala Arg Asp Arg Leu Pro Gin Met Ser Ser Pro 145 150 155 Met He Ser Ser His Ala Asp He Lys Leu Ser Leu Lys Asn Phe Lys 160 165 170 Ala Leu Val Tyr His Val Gly Asp Thr He Asn Val Ser Thr Ala Val 175 180 185 190 He Leu Gly Pro Ser Pro Glu He Phe Thr Leu Glu Phe Arg Val Leu 195 200 205 Phe Leu Arg Tyr Asn Pro Thr Cys Lys Phe Val Thr He Tyr Glu Pro 210 215 220 Cys He Phe His Pro Lys Glu Pro Glu Cys He Thr Thr Ala Glu Gin 225 230 235 Ser Val Cys His Phe Ala Ser Asn He Asp He Leu Gin He Ala Ala - 240 245 250 Ala Arg Ser Glu Asn Cys Ser Thr Gly Tyr Arg Arg Cys He Tyr Asp 255 * 260 265 270 Thr Ala He Asp Glu Ser Val Gin Ala Arg Leu Thr Phe He Glu Pro 275 280 285 Gly He Pro Ser Phe Lys Met Lys Asp Val Gin Val Asp Asp Ala Gly 290 295 300 Leu Tyr Val Val Val Ala Leu Tyr Asn Gly Arg Pro Ser Ala Trp Thr 305 310 315 Tyr He Tyr Leu Ser Thr Val Glu Thr Tyr Leu Asn Val Tyr Glu Asn 320 325 330 Tyr His Lys Pro Gly Phe Gly Tyr Lys Ser Phe Leu Gin Asn Ser Ser 335 340 345 350 He Val Asp Glu Asn Glu Ala Ser Asp Trp Ser Ser Ser Ser He Lys 355 360 365 Arg Arg Asn Asn Gly Thr He He Tyr Asp He Leu Leu Thr Ser Leu 370 375 380 Ser He Gly Ala He He He Val He Val Gly Gly Val Cys He Ala 385 390 395 He Leu He Arg Arg Arg Arg Arg Arg Arg Thr Arg Gly Leu Phe Asp 400 405 410 Glu Tyr Pro Lys Tyr Met Thr Leu Pro Gly Asn Asp Leu Gly Gly Met 415 420 425 430 Asn Val Pro Tyr Asp Asn Thr Cys Ser Gly Asn Gin Val Glu Tyr Tyr 435 440 445 Gin Glu Lys Ser Ala Lys Met Lys Arg Met Gly Ser Gly Tyr Thr Ala 450 455 460 Trp Leu Lys Asn Asp Met Pro Lys He Arg Lys Arg Leu Asp Leu Tyr 465 470 475 His End

Claims: WE CLAIM: -1- A 2.53 Kb segment of DNA with a gene coding MDV glycoprotein E (gE) precursor, between a 8488 and 9978 bp sequence of Marek's disease herpesvirus DNA and identified as part of SEQ ID No:l, and containing potential promoter 5 sequences up to 400 nucleotides 5' of each gene and subfragments of the DNA which selectively recognize the DNA when in the form of a probe. -2- The segment of Claim 1 wherein the glycoprotein encoded contains 497 amino acids . -3- The substantially pure glycoprotein gE precursor which comprises: Met Cys Val Phe Gin He Leu He He Val Thr Thr He Lys Val Ala - 15 - 10 -5 Gly Thr Ala Asn He Asn His He Asp Val Pro Ala Gly His Ser Ala 1 5 10 Thr Thr Thr He Pro Arg Tyr Pro Pro Val Val Asp Gly Thr Leu Tyr 15 20 25 30 Thr Glu Thr Trp Thr Trp He Pro Asn His Cys Asn Glu Thr Ala Thr 10 35 40 45 Gly Tyr Val Cys Leu Glu Ser Ala His Cys Phe Thr Asp Leu He Leu 50 55 60 Gly Val Ser Cys Met Arg Tyr Ala Asp Glu He Val Leu Arg Thr As p 65 70 75 ! • -> Lys Phe He Val Asp Ala Gly Ser He Lys Gin He Glu Ser Leu Ser 80 85 90 Leu Asn Gly Val Pro Asn He Phe Leu Ser Thr Lys Ala Ser Asn L y s 95 100 105 no Leu Glu He Leu Asn Ala Ser Leu Gin Asn Ala Gly He Tyr He Arg 20 1 120 125 Tyr Ser Arg Asn Gly Thr Arg Thr Ala Lys Leu Asp Val Val Val Val 130 135 140 Gly Val Leu Gly Gin Ala Arg Asp Arg Leu Pro Gin Met Ser Ser Pro 145 150 155 Met He Ser Ser His Ala Asp He Lys Leu Ser Leu Lys Asn Phe Lys 160 165 170 Ala Leu Val Tyr His Val Gly Asp Thr He Asn Val Ser Thr Ala Val 175 180 185 190 He Leu Gly Pro Ser Pro Glu He Phe Thr Leu Glu Phe Arg Val Leu 195 200 205 Phe Leu Arg Tyr Asn Pro Thr Cys Lys Phe Val Thr He Tyr Glu Pro 210 215 220 Cys He Phe His Pro Lys Glu Pro Glu Cys He Thr Thr Ala Glu Gin 225 230 235 Ser Val Cys His Phe Ala Ser Asn He Asp He Leu Gin He Ala Ala 240 245 250 Ala Arg Ser Glu Asn Cys Ser Thr Gly Tyr Arg Arg Cys He Tyr Asp 255 260 265 270 Thr Ala He Asp Glu Ser Val Gin Ala Arg Leu Thr Phe He Glu Pro 275 280 285 Gly He Pro Ser Phe Lys Met Lys Asp Val Gin Val Asp Asp Ala Gly 290 295 300 Leu Tyr Val Val Val Ala Leu Tyr Asn Gly Arg Pro Ser Ala Trp Thr 305 310 315 Tyr He Tyr Leu Ser Thr Val Glu Thr Tyr Leu Asn Val Tyr Glu Asn 320 325 330 Tyr His Lys Pro Gly Phe Gly Tyr Lys Ser Phe Leu Gin Asn Ser Ser 335 340 345 350 He Val Asp Glu Asn Glu Ala Ser Asp Trp Ser Ser Ser Ser He Lys 355 360 365 Arg Arg Asn Asn Gly Thr He He Tyr Asp He Leu Leu Thr Ser Leu 370 375 380 Ser He Gly Ala He He He Val He Val Gly Gly Val Cys He Ala 385 390 395 He Leu He Aςg Arg Arg Arg Arg Arg Arg Thr Arg Gly Leu Phe Asp 400 405 410 Glu Tyr Pro Lys Tyr Met Thr Leu Pro Gly Asn Asp Leu Gly Gly Met 415 420 425 430 Asn Val Pro Tyr Asp Asn Thr Cys Ser Gly Asn Gin Val Glu Tyr Tyr 435 440 445 Gin Glu Lys Ser Ala Lys Met Lys Arg Met Gly Ser Gly Tyr Thr Ala 450 455 460 Trp Leu Lys Asn Asp Met Pro Lys He Arg Lys Arg Leu Asp Leu Tyr 465 470 475 His End -4- A method for reducing pathogenicity or virulence of a Marek's disease herpesvirus whereby a gene which encodes for a glycoprotein selected from glycoproteins I and E is altered. -5- In a method for producing a virus vector vaccine, for use in ^ vivo, or an in ^ vitro expression vector, for a protein which produces antibodies against Marek's disease by providing in the vaccine or vector a segment of DNA from the genome of a Marek's disease herpesvirus that encodes a protein producing an antibody response in birds, the improvement which comprises: inserting into the vaccine or vector a segment of DNA containing all or part of a gene encoding a glycoprotein selected from the group consisting of gD, gl and gE of the Marek's disease herpesvirus. -6- A method for providing foreign genes in a Marek's disease herpesvirus which comprises inserting the foreign gene into a region of DNA of the herpesvirus which encodes a non-essential protein selected from the group consisting of gl and gE. -7- A segment of DNA of Marek's disease herpesvirus (MDV) genome with genes encoding multiple glycoproteins between a 1 and 8799 nucleotide sequence and identified as SEQ ID NO:l, and optionally containing regulatory sequences up to 400 nucleotides 5' of each gene as shown in Figure 2 and subsegments of the DNA which selectively recognize portions of the segment of the DNA when in the form of a probe. -8- An EcoRl I segment of Marek's disease herpesvirus genome encoding MDV glycoprotein D (gD) precursor and regulatory sequences and subsegments of the DNA which selectively recognize the DNA when in the form of a probe. -9- A 1.75 kbp Ncol-Sstll segment of DNA of Marek's disease herpesvirus with a gene encoding MDV gD and containing a 5' regulatory region with the gene and subsegments of the DNA which selectively recognize the DNA when in the form of a probe. -10- A segment of DNA encoding MDV gD precursor, between a 5964 and 7175 bp nucleotide sequence of Marek's disease herpesvirus and identified as part of SEQ ID No:l, and optionally containing a 5' regulatory reσion of up to 400 bp in length as shown in Figure 2 and sx. segments of the segment of DNA which selectively recognize the DNA when the form of a probe. -11- The segment of Claim 10 wherein the glycoprotein encoded contains 403 amino acids. -12- A segment of DNA with a gene encoding a glycoprotein I (gl) precursor between a 7282 and 8349 bp DNA sequence of Marek's disease herpesvirus and identified as part of SEQ ID No:l, and optionally containing a 5* regulatory region with the gene of up to 400 bp in length as shown in Figure 2 and subfragments of the segment of DNA which selectively recognize the DNA when in the form of a probe. -13- The segment of Claim 1 herein the glycoprotein encoded contains 355 amino acids. -l_t- A segment of DNA with a gene encoding a part of MDV glycoprotein E (gE) precursor, between a 8488 and 8799 bp DNA sequence of Marek's disease herpesvirus and identified as part of SEQ ID No:l, and optionally containing a 5* regulatory region with the gene of up to 400 bp in length, as shown in Figure 2 and subfragments of the DNA which selectively recognize the DNA when in the form of a probe. -15- The segment of Claim 14. wherein the glycoprotein encoded contains 104 amino acids. -16" The substantially pure glycoprotein gl precursor which comprises: Met Tyr Val Leu Gin Leu Leu Phe Trp He Arg Leu Phe Arg Gly He -15 -10 -5 Trp Ser He Val Tyr Thr Gly Thr Ser Val Thr Leu Ser Thr Asp Gin 1 5 10 Ser Ala Leu Val Ala Phe Arg Gly Leu Asp Lys Met Val Asn Val Arg 15 20 25 30 Gly Gin Leu Leu Phe Leu Gly Asp Gin Thr Arg Thr Ser Ser Tyr Thr 35 40 45 Gly Thr Thr Glu He Leu Lys Trp Asp Glu Glu Tyr Lys Cys Tyr Ser 50 55 60 Val Leu His Ala Thr Ser Tyr Met Asp Cys Pro Ala He Asp Ala Thr 65 70 75 Val Phe Arg Gly Cys Arg Asp Ala Val Val Tyr Ala Gin Pro His Gly 80 85 90 Arg Val Gin Pro Phe Pro Glu Lys Gly Thr Leu Leu Arg He Val Glu 95 100 105 110 Pro Arg Val Ser Asp Thr Gly Ser Tyr Tyr He Arg Val Ser Leu Ala 115 ' 120 125 Gly Arg Asn Met Ser Asp He Phe Arg Met Val Val He He Arg Ser 130 135 140 Ser Lys Ser Trp Ala Cys Asn His Ser Ala Ser Ser Phe Gin Ala His 145 150 155 Lys Cys He Arg Tyr Val Asp Arg Met Ala Phe Glu Asn Tyr Leu He 160 165 170 Gly His Val Gly Asn Leu Leu Asp Ser Asp Ser Glu Leu His Ala He 175 180 185 190 Tyr Asn He Thr Pro Gin Ser He Ser Thr Asp He Asn He Val Thr 195 200 205 Thr Pro Phe Tyr Asp Asn Ser Gly Thr He Tyr Ser Pro Thr Val Phe 210 215 220 Asn Leu Phe Asn Asn Asn Ser His Val Asp Ala Met Asn Ser Thr Gly 225 230 235 Met Trp Asn Thr Val Leu Lys Tyr Thr Leu Pro Arg Leu He Tyr Phe 240 245 250 Ser Thr Met He Val Leu Cys He He Ala Leu Ala He Tyr Leu Val 255 260 265 270 Cys Glu Arg Cys Arg Ser Pro His Arg Arg He Tyr He Gly Glu Pro 275 280 285 Arg Ser Asp Glu Ala Pro Leu lie Thr Ser Ala Val Asn Glu Ser Phe " 290 295 300 Gin Tyr Asp Tyr Asn Val Lys Glu Thr Pro Ser Asp Val He Glu Lys 305 310 315 Glu Leu Met Glu Lys Leu Lys Lys Lys Val Glu Leu Leu Glu Arg Glu 320 325 330 Glu Cys Val 335 -17- The substantially pure glycoprotein gD partial precursor which comprises : Met Asn Arg Tyr Arg Tyr Glu Ser lie Phe Phe Arg Tyr lie Ser Ser -30 -25 -20 -15 Thr Arg Met He Leu He He Cys Leu Leu Leu Gly Thr Gly Asp Met -10 -5 1 Ser Ala Met Gly Leu Lys Lys Asp Asn Ser Pro He He Pro Thr Leu 5 10 15 His Pro Lys Gly Asn Glu Asn Leu Arg Ala Thr Leu Asn Glu Tyr Lys 20 25 .30 He Pro Ser Pro Leu Phe Asp Thr Leu Asp Asn Ser Tyr Glu Thr Lys 35 40 45 50 His Val He Tyr Thr Asp Asn Cys Ser Phe Ala Val Leu Asn Pro Phe 55 60 65 Gly Asp Pro Lys Tyr Thr Leu Leu Ser Leu Leu Leu Met Gly Arg Arg 70 75 80 Lys Tyr Asp Ala Leu Val Ala Trp Phe Val Leu Gly Arg Ala Cys Gly 85 90 95 Arg Pro He Tyr Leu Arg Glu Tyr Ala Asn Cys Ser Thr Asn Glu Pro 100 105 110 Phe Gly Thr Cys Lys Leu Lys Ser Leu Gly Trp Trp Asp Arg Arg Tyr 115 120 125 130 Ala Met Thr Ser Tyr He Asp Arg Asp Glu Leu Lys Leu He He Ala 135 140 145 Ala Pro Ser Arg Glu Leu Ser Gly Leu Tyr Thr Arg Leu He He He 150 155 160 Asn Gly Glu Pro lie Ser Ser Asp lie Leu Leu Thr Val Lys Gly Thr 165 170 175 Cys Ser Phe Ser Arg Arg Gly He Lys Asp Asn Lys Leu Cys Lys Pro 180 185 190 Phe Ser Phe Phe Val Asn Gly Thr Thr Arg Leu Leu Asp Met Val Arg 195 200 205 210 Thr Gly Thr Pro Arg Ala His Glu Glu Asn Val Lys Gin Trp Leu Glu 215 220 225 Arg Asn Gly Gly Lys His Leu Pro He Val Val Glu Thr Ser Met Gin 230 235 240 Gin Val Ser Asn Leu Pro Arg Ser Phe Arg Asp Ser Tyr Leu Lys Ser 245 250 255 Pro Asp Asp Asp Lys Tyr Asn Asp Val Lys Met Thr Ser Ala Thr Thr 260 265 270 Asn Asn He Thr Thr Ser Val Asp Gly Tyr Thr Gly Leu Thr Asn Arg 275 280 285 290 Pro Glu Asp Phe Glu Lys Ala Pro Tyr He Thr Lys Arg Pro He He 295 300 305 Ser Val Glu Glu Ala Ser Ser Gin Ser Pro Lys He Ser Thr Glu Lys 310 315 320 Lys Ser Arg Thr Gin He He He Ser Leu Val Val Leu Cys Val Met 325 330 335 Phe Cys Phe He Val lie Gly Ser Gly lie Trp He Leu Arg Lys His 340 345 350 Arg Lys Thr Val Met Tyr Asp Arg Arg Arg Pro Ser Arg Arg Ala Tyr 355 360 365 370 Ser Arg Leu -18- The substantially pure glycoprotein gE precursor which comprises: Val Phe Gin He Leu He He Val Thr Thr He Lys Val Ala -15 -10 -5 Ala Asn He Asn His He Asp Val Pro Arg Gly His Ser Ala 1 5 10 Thr He Pro Arg Tyr Pro Pro Val Val Asp Gly Thr Leu Tyr 20 25 30 Thr Trp Thr Trp He Pro Asn His Cys Asn Glu Thr Ala Thr 35 40 45 Val Cys Leu Glu Ser Ala His Cys Phe Thr Asp Leu He Leu 50 55 60 Ser Cys Met Arg Tyr Ala Asp Glu He Val Leu Arg Thr Asp 65 70 75 He Val Asp Ala Gly Ser 85 - 19- A 5 ' regulatory region for glycoprotein gD between 5664 and 5963 nucleotide sequence as shown in Figure 2 . -20- A 5 ' regulatory region for glycoprotein gE between 8088 and 8487 nucleotide sequence as shown in Figure 2 . -21 - A regulatory region for glycoprotein gl between 6882 and 7281 nucleotide sequence as shown in Figure 2 .

Inventors: BRUNOVSKIS PETER, COUSSENS PAUL M, VELICER LELAND F, BRUNOVSKIS, PETER, COUSSENS, PAUL, M., VELICER, LELAND, F.
Applicants: UNIV MICHIGAN, MICHIGAN STATE UNIVERSITY
Application year: 1991
Main classification: C12N15
IPC codes: A61K38, C07K14, C12N7, C12N15, C12R1