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. 1991 Nov;65(11):5744–5750. doi: 10.1128/jvi.65.11.5744-5750.1991

Structure and genetic variability of envelope glycoproteins of two antigenic variants of caprine arthritis-encephalitis lentivirus.

D P Knowles Jr 1, W P Cheevers 1, T C McGuire 1, A L Brassfield 1, W G Harwood 1, T A Stem 1
PMCID: PMC250234  PMID: 1656067

Abstract

To define the structure of the caprine arthritis-encephalitis virus (CAEV) env gene and characterize genetic changes which occur during antigenic variation, we sequenced the env genes of CAEV-63 and CAEV-Co, two antigenic variants of CAEV defined by serum neutralization. The deduced primary translation product of the CAEV env gene consists of a 60- to 80-amino-acid signal peptide followed by an amino-terminal surface protein (SU) and a carboxy-terminal transmembrane protein (TM) separated by an Arg-Lys-Lys-Arg cleavage site. The signal peptide cleavage site was verified by amino-terminal amino acid sequencing of native CAEV-63 SU. In addition, immunoprecipitation of [35S]methionine-labeled CAEV-63 proteins by sera from goats immunized with recombinant vaccinia virus expressing the CAEV-63 env gene confirmed that antibodies induced by env-encoded recombinant proteins react specifically with native virion SU and TM. The env genes of CAEV-63 and CAEV-Co encode 28 conserved cysteines and 25 conserved potential N-linked glycosylation sites. Nucleotide sequence variability results in 62 amino acid changes and one deletion within the SU and 34 amino acid changes within the TM.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Adams D. S., Gogolewski R. P., Barbet A. F., Cheevers W. P. Identification of caprine arthritis-encephalitis retrovirus proteins in immunodiffusion precipitin lines. J Gen Virol. 1985 May;66(Pt 5):1139–1143. doi: 10.1099/0022-1317-66-5-1139. [DOI] [PubMed] [Google Scholar]
  2. Allan J. S., Coligan J. E., Barin F., McLane M. F., Sodroski J. G., Rosen C. A., Haseltine W. A., Lee T. H., Essex M. Major glycoprotein antigens that induce antibodies in AIDS patients are encoded by HTLV-III. Science. 1985 May 31;228(4703):1091–1094. doi: 10.1126/science.2986290. [DOI] [PubMed] [Google Scholar]
  3. Ball J. M., Rao V. S., Robey W. G., Issel C. J., Montelaro R. C. Lentivirus antigen purification and characterization: isolation of equine infectious anemia virus gag and env proteins in one step by reverse phase HPLC and application to human immunodeficiency virus glycoproteins. J Virol Methods. 1988 Mar-Apr;19(3-4):265–277. doi: 10.1016/0166-0934(88)90021-3. [DOI] [PubMed] [Google Scholar]
  4. Braun M. J., Clements J. E., Gonda M. A. The visna virus genome: evidence for a hypervariable site in the env gene and sequence homology among lentivirus envelope proteins. J Virol. 1987 Dec;61(12):4046–4054. doi: 10.1128/jvi.61.12.4046-4054.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Chakrabarti S., Brechling K., Moss B. Vaccinia virus expression vector: coexpression of beta-galactosidase provides visual screening of recombinant virus plaques. Mol Cell Biol. 1985 Dec;5(12):3403–3409. doi: 10.1128/mcb.5.12.3403. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Cheevers W. P., Knowles D. P., McGuire T. C., Cunningham D. R., Adams D. S., Gorham J. R. Chronic disease in goats orally infected with two isolates of the caprine arthritis-encephalitis lentivirus. Lab Invest. 1988 May;58(5):510–517. [PubMed] [Google Scholar]
  7. Cheevers W. P., Roberson S., Klevjer-Anderson P., Crawford T. B. Characterization of caprine arthritis-encephalitis virus: a retrovirus of goats. Arch Virol. 1981;67(1):111–117. doi: 10.1007/BF01314610. [DOI] [PubMed] [Google Scholar]
  8. Cheevers W. P., Stem T. A., Knowles D. P., McGuire T. C. Precursor polypeptides of caprine arthritis-encephalitis lentivirus structural proteins. J Gen Virol. 1988 Mar;69(Pt 3):675–681. doi: 10.1099/0022-1317-69-3-675. [DOI] [PubMed] [Google Scholar]
  9. Collard M. W., Griswold M. D. Biosynthesis and molecular cloning of sulfated glycoprotein 2 secreted by rat Sertoli cells. Biochemistry. 1987 Jun 16;26(12):3297–3303. doi: 10.1021/bi00386a008. [DOI] [PubMed] [Google Scholar]
  10. Crawford T. B., Adams D. S., Cheevers W. P., Cork L. C. Chronic arthritis in goats caused by a retrovirus. Science. 1980 Feb 29;207(4434):997–999. doi: 10.1126/science.6153243. [DOI] [PubMed] [Google Scholar]
  11. Devereux J., Haeberli P., Smithies O. A comprehensive set of sequence analysis programs for the VAX. Nucleic Acids Res. 1984 Jan 11;12(1 Pt 1):387–395. doi: 10.1093/nar/12.1part1.387. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Ellis T. M., Wilcox G. E., Robinson W. F. Antigenic variation of caprine arthritis-encephalitis virus during persistent infection of goats. J Gen Virol. 1987 Dec;68(Pt 12):3145–3152. doi: 10.1099/0022-1317-68-12-3145. [DOI] [PubMed] [Google Scholar]
  13. Gallaher W. R., Ball J. M., Garry R. F., Griffin M. C., Montelaro R. C. A general model for the transmembrane proteins of HIV and other retroviruses. AIDS Res Hum Retroviruses. 1989 Aug;5(4):431–440. doi: 10.1089/aid.1989.5.431. [DOI] [PubMed] [Google Scholar]
  14. Garvey K. J., Oberste M. S., Elser J. E., Braun M. J., Gonda M. A. Nucleotide sequence and genome organization of biologically active proviruses of the bovine immunodeficiency-like virus. Virology. 1990 Apr;175(2):391–409. doi: 10.1016/0042-6822(90)90424-p. [DOI] [PubMed] [Google Scholar]
  15. George D. G., Barker W. C., Hunt L. T. The protein identification resource (PIR). Nucleic Acids Res. 1986 Jan 10;14(1):11–15. doi: 10.1093/nar/14.1.11. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Gogolewski R. P., Adams D. S., McGuire T. C., Banks K. L., Cheevers W. P. Antigenic cross-reactivity between caprine arthritis-encephalitis, visna and progressive pneumonia viruses involves all virion-associated proteins and glycoproteins. J Gen Virol. 1985 Jun;66(Pt 6):1233–1240. doi: 10.1099/0022-1317-66-6-1233. [DOI] [PubMed] [Google Scholar]
  17. Gubler U., Hoffman B. J. A simple and very efficient method for generating cDNA libraries. Gene. 1983 Nov;25(2-3):263–269. doi: 10.1016/0378-1119(83)90230-5. [DOI] [PubMed] [Google Scholar]
  18. Hess J. L., Pyper J. M., Clements J. E. Nucleotide sequence and transcriptional activity of the caprine arthritis-encephalitis virus long terminal repeat. J Virol. 1986 Nov;60(2):385–393. doi: 10.1128/jvi.60.2.385-393.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Hines S. A., McElwain T. F., Buening G. M., Palmer G. H. Molecular characterization of Babesia bovis merozoite surface proteins bearing epitopes immunodominant in protected cattle. Mol Biochem Parasitol. 1989 Nov;37(1):1–9. doi: 10.1016/0166-6851(89)90096-0. [DOI] [PubMed] [Google Scholar]
  20. Hunkapiller M. W., Lujan E., Ostrander F., Hood L. E. Isolation of microgram quantities of proteins from polyacrylamide gels for amino acid sequence analysis. Methods Enzymol. 1983;91:227–236. doi: 10.1016/s0076-6879(83)91019-4. [DOI] [PubMed] [Google Scholar]
  21. Jackson M. K., Knowles D. P., Stem T. A., Harwood W. G., Robinson M. M., Cheevers W. P. Genetic structure of the pol-env region of the caprine arthritis-encephalitis lentivirus genome. Virology. 1991 Jan;180(1):389–394. doi: 10.1016/0042-6822(91)90044-c. [DOI] [PubMed] [Google Scholar]
  22. Johnson G. C., Barbet A. F., Klevjer-Anderson P., McGuire T. C. Preferential immune response to virion surface glycoproteins by caprine arthritis-encephalitis virus-infected goats. Infect Immun. 1983 Aug;41(2):657–665. doi: 10.1128/iai.41.2.657-665.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Klevjer-Anderson P., Cheevers W. P. Characterization of the infection of caprine synovial membrane cells by the retrovirus caprine arthritis-encephalitis virus. Virology. 1981 Apr 15;110(1):113–119. doi: 10.1016/0042-6822(81)90012-x. [DOI] [PubMed] [Google Scholar]
  24. Knowles D., Jr, Cheevers W., McGuire T., Stem T., Gorham J. Severity of arthritis is predicted by antibody response to gp135 in chronic infection with caprine arthritis-encephalitis virus. J Virol. 1990 May;64(5):2396–2398. doi: 10.1128/jvi.64.5.2396-2398.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Kozak M. Point mutations define a sequence flanking the AUG initiator codon that modulates translation by eukaryotic ribosomes. Cell. 1986 Jan 31;44(2):283–292. doi: 10.1016/0092-8674(86)90762-2. [DOI] [PubMed] [Google Scholar]
  26. Lennarz W. J. Lipid linked sugars in glycoprotein synthesis. Science. 1975 Jun 6;188(4192):986–991. doi: 10.1126/science.167438. [DOI] [PubMed] [Google Scholar]
  27. Mackett M., Smith G. L., Moss B. General method for production and selection of infectious vaccinia virus recombinants expressing foreign genes. J Virol. 1984 Mar;49(3):857–864. doi: 10.1128/jvi.49.3.857-864.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. McGuire T. C., Adams D. S., Johnson G. C., Klevjer-Anderson P., Barbee D. D., Gorham J. R. Acute arthritis in caprine arthritis-encephalitis virus challenge exposure of vaccinated or persistently infected goats. Am J Vet Res. 1986 Mar;47(3):537–540. [PubMed] [Google Scholar]
  29. McGuire T. C., Norton L. K., O'Rourke K. I., Cheevers W. P. Antigenic variation of neutralization-sensitive epitopes of caprine arthritis-encephalitis lentivirus during persistent arthritis. J Virol. 1988 Sep;62(9):3488–3492. doi: 10.1128/jvi.62.9.3488-3492.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Michelson A. M., Orkin S. H. Characterization of the homopolymer tailing reaction catalyzed by terminal deoxynucleotidyl transferase. Implications for the cloning of cDNA. J Biol Chem. 1982 Dec 25;257(24):14773–14782. [PubMed] [Google Scholar]
  31. Modrow S., Hahn B. H., Shaw G. M., Gallo R. C., Wong-Staal F., Wolf H. Computer-assisted analysis of envelope protein sequences of seven human immunodeficiency virus isolates: prediction of antigenic epitopes in conserved and variable regions. J Virol. 1987 Feb;61(2):570–578. doi: 10.1128/jvi.61.2.570-578.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Narayan O., Clements J. E., Strandberg J. D., Cork L. C., Griffin D. E. Biological characterization of the virus causing leukoencephalitis and arthritis in goats. J Gen Virol. 1980 Sep;50(1):69–79. doi: 10.1099/0022-1317-50-1-69. [DOI] [PubMed] [Google Scholar]
  33. Olmsted R. A., Hirsch V. M., Purcell R. H., Johnson P. R. Nucleotide sequence analysis of feline immunodeficiency virus: genome organization and relationship to other lentiviruses. Proc Natl Acad Sci U S A. 1989 Oct;86(20):8088–8092. doi: 10.1073/pnas.86.20.8088. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Payne S. L., Fang F. D., Liu C. P., Dhruva B. R., Rwambo P., Issel C. J., Montelaro R. C. Antigenic variation and lentivirus persistence: variations in envelope gene sequences during EIAV infection resemble changes reported for sequential isolates of HIV. Virology. 1987 Dec;161(2):321–331. doi: 10.1016/0042-6822(87)90124-3. [DOI] [PubMed] [Google Scholar]
  35. Payne S. L., Rushlow K., Dhruva B. R., Issel C. J., Montelaro R. C. Localization of conserved and variable antigenic domains of equine infectious anemia virus envelope glycoproteins using recombinant env-encoded protein fragments produced in Escherichia coli. Virology. 1989 Oct;172(2):609–615. doi: 10.1016/0042-6822(89)90203-1. [DOI] [PubMed] [Google Scholar]
  36. Pearson W. R., Lipman D. J. Improved tools for biological sequence comparison. Proc Natl Acad Sci U S A. 1988 Apr;85(8):2444–2448. doi: 10.1073/pnas.85.8.2444. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Phillips T. R., Talbott R. L., Lamont C., Muir S., Lovelace K., Elder J. H. Comparison of two host cell range variants of feline immunodeficiency virus. J Virol. 1990 Oct;64(10):4605–4613. doi: 10.1128/jvi.64.10.4605-4613.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Pinter A., Honnen W. J., Tilley S. A., Bona C., Zaghouani H., Gorny M. K., Zolla-Pazner S. Oligomeric structure of gp41, the transmembrane protein of human immunodeficiency virus type 1. J Virol. 1989 Jun;63(6):2674–2679. doi: 10.1128/jvi.63.6.2674-2679.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Pyper J. M., Clements J. E., Gonda M. A., Narayan O. Sequence homology between cloned caprine arthritis encephalitis virus and visna virus, two neurotropic lentiviruses. J Virol. 1986 May;58(2):665–670. doi: 10.1128/jvi.58.2.665-670.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Rey M. A., Laurent A. G., McClure J., Krust B., Montagnier L., Hovanessian A. G. Transmembrane envelope glycoproteins of human immunodeficiency virus type 2 and simian immunodeficiency virus SIV-mac exist as homodimers. J Virol. 1990 Feb;64(2):922–926. doi: 10.1128/jvi.64.2.922-926.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Roberson S. M., Cheevers W. P. A physical map of caprine arthritis-encephalitis provirus. Virology. 1984 Apr 30;134(2):489–492. doi: 10.1016/0042-6822(84)90318-0. [DOI] [PubMed] [Google Scholar]
  42. Rusche J. R., Javaherian K., McDanal C., Petro J., Lynn D. L., Grimaila R., Langlois A., Gallo R. C., Arthur L. O., Fischinger P. J. Antibodies that inhibit fusion of human immunodeficiency virus-infected cells bind a 24-amino acid sequence of the viral envelope, gp120. Proc Natl Acad Sci U S A. 1988 May;85(9):3198–3202. doi: 10.1073/pnas.85.9.3198. [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. Rushlow K., Olsen K., Stiegler G., Payne S. L., Montelaro R. C., Issel C. J. Lentivirus genomic organization: the complete nucleotide sequence of the env gene region of equine infectious anemia virus. Virology. 1986 Dec;155(2):309–321. doi: 10.1016/0042-6822(86)90195-9. [DOI] [PubMed] [Google Scholar]
  44. Saltarelli M., Querat G., Konings D. A., Vigne R., Clements J. E. Nucleotide sequence and transcriptional analysis of molecular clones of CAEV which generate infectious virus. Virology. 1990 Nov;179(1):347–364. doi: 10.1016/0042-6822(90)90303-9. [DOI] [PubMed] [Google Scholar]
  45. Simmonds P., Balfe P., Ludlam C. A., Bishop J. O., Brown A. J. Analysis of sequence diversity in hypervariable regions of the external glycoprotein of human immunodeficiency virus type 1. J Virol. 1990 Dec;64(12):5840–5850. doi: 10.1128/jvi.64.12.5840-5850.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  46. Sonigo P., Alizon M., Staskus K., Klatzmann D., Cole S., Danos O., Retzel E., Tiollais P., Haase A., Wain-Hobson S. Nucleotide sequence of the visna lentivirus: relationship to the AIDS virus. Cell. 1985 Aug;42(1):369–382. doi: 10.1016/s0092-8674(85)80132-x. [DOI] [PubMed] [Google Scholar]
  47. Starcich B. R., Hahn B. H., Shaw G. M., McNeely P. D., Modrow S., Wolf H., Parks E. S., Parks W. P., Josephs S. F., Gallo R. C. Identification and characterization of conserved and variable regions in the envelope gene of HTLV-III/LAV, the retrovirus of AIDS. Cell. 1986 Jun 6;45(5):637–648. doi: 10.1016/0092-8674(86)90778-6. [DOI] [PubMed] [Google Scholar]
  48. Talbott R. L., Sparger E. E., Lovelace K. M., Fitch W. M., Pedersen N. C., Luciw P. A., Elder J. H. Nucleotide sequence and genomic organization of feline immunodeficiency virus. Proc Natl Acad Sci U S A. 1989 Aug;86(15):5743–5747. doi: 10.1073/pnas.86.15.5743. [DOI] [PMC free article] [PubMed] [Google Scholar]
  49. Veronese F. D., DeVico A. L., Copeland T. D., Oroszlan S., Gallo R. C., Sarngadharan M. G. Characterization of gp41 as the transmembrane protein coded by the HTLV-III/LAV envelope gene. Science. 1985 Sep 27;229(4720):1402–1405. doi: 10.1126/science.2994223. [DOI] [PubMed] [Google Scholar]

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