Skip to main content
NCBI home page
Journal of Virology logoLink to Journal of Virology
. 1995 Apr;69(4):2110–2118. doi: 10.1128/jvi.69.4.2110-2118.1995

Structural analysis of the principal immunodominant domain of the feline immunodeficiency virus transmembrane glycoprotein.

G Pancino 1, L Camoin 1, P Sonigo 1
PMCID: PMC188877  PMID: 7884857

Abstract

In the transmembrane envelope glycoprotein (TM) of lentiviruses, including human immunodeficiency virus type 1 (HIV-1) and feline immunodeficiency virus (FIV), two cysteine residues, conserved in most retroviruses, are thought to form a loop containing five to seven amino acids. These elements make up a B-cell epitope recognized by nearly 100% of sera from infected patients or animals, designated the principal immunodominant domain (PID). The PID amino acid sequences are highly conserved between isolates of the same lentivirus but are unrelated, except for the two cysteines, when divergent lentiviruses are compared. The aim of this study was to analyze the relationship between amino acid sequence in the PID and envelope function. We introduced two kinds of mutations in the PID of FIV: mutations which impeded the formation of a loop and mutations which substituted the sequence of FIV with the corresponding sequences from other lentiviruses, HIV-1, visna virus, and equine infectious anemia virus. We analyzed antibody recognition, processing, and fusogenic properties of the modified envelopes, using two methods of Env expression: a cell-free expression system and transfection of a feline fibroblast cell line with gag-pol-deleted FIV proviruses. Most mutations in the PID of FIV severely affected envelope processing and abolished syncytium formation. Only the chimeric envelope containing the HIV-1 PID sequence was correctly processed and maintained the capacity to induce syncytium formation, although less efficiently than the wild-type envelope. We computed three-dimensional structural models of the PID, which were consistent with mutagenesis data and confirmed the similarity of FIV and HIV-1 PID structures, despite their divergence in amino acid sequence. Considering these results, we discussed the respective importance of selection exerted by functional requirements or host antibodies to explain the observed variations of the PIDs in lentiviruses.

Full Text

The Full Text of this article is available as a PDF (511.4 KB).

Selected References

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

  1. Alizon M., Wain-Hobson S., Montagnier L., Sonigo P. Genetic variability of the AIDS virus: nucleotide sequence analysis of two isolates from African patients. Cell. 1986 Jul 4;46(1):63–74. doi: 10.1016/0092-8674(86)90860-3. [DOI] [PubMed] [Google Scholar]
  2. Avrameas A., Guillet J. G., Chouchane L., Moraillon A., Sonigo P., Strosberg A. D. Localisation of three epitopes of the env protein of feline immunodeficiency virus. Mol Immunol. 1992 May;29(5):565–572. doi: 10.1016/0161-5890(92)90192-z. [DOI] [PubMed] [Google Scholar]
  3. Avrameas A., Strosberg A. D., Moraillon A., Sonigo P., Pancino G. Serological diagnosis of feline immunodeficiency virus infection based on synthetic peptides from Env glycoproteins. Res Virol. 1993 May-Jun;144(3):209–218. doi: 10.1016/s0923-2516(06)80031-2. [DOI] [PubMed] [Google Scholar]
  4. Bertoni G., Zahno M. L., Zanoni R., Vogt H. R., Peterhans E., Ruff G., Cheevers W. P., Sonigo P., Pancino G. Antibody reactivity to the immunodominant epitopes of the caprine arthritis-encephalitis virus gp38 transmembrane protein associates with the development of arthritis. J Virol. 1994 Nov;68(11):7139–7147. doi: 10.1128/jvi.68.11.7139-7147.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Brody B. A., Hunter E. Mutations within the env gene of Mason-Pfizer monkey virus: effects on protein transport and SU-TM association. J Virol. 1992 Jun;66(6):3466–3475. doi: 10.1128/jvi.66.6.3466-3475.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Bruccoleri R. E., Karplus M. Conformational sampling using high-temperature molecular dynamics. Biopolymers. 1990 Dec;29(14):1847–1862. doi: 10.1002/bip.360291415. [DOI] [PubMed] [Google Scholar]
  7. Bugge T. H., Lindhardt B. O., Hansen L. L., Kusk P., Hulgaard E., Holmbäck K., Klasse P. J., Zeuthen J., Ulrich K. Analysis of a highly immunodominant epitope in the human immunodeficiency virus type 1 transmembrane glycoprotein, gp41, defined by a human monoclonal antibody. J Virol. 1990 Sep;64(9):4123–4129. doi: 10.1128/jvi.64.9.4123-4129.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Chong Y. H., Ball J. M., Issel C. J., Montelaro R. C., Rushlow K. E. Analysis of equine humoral immune responses to the transmembrane envelope glycoprotein (gp45) of equine infectious anemia virus. J Virol. 1991 Feb;65(2):1013–1018. doi: 10.1128/jvi.65.2.1013-1018.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Dedera D., Gu R. L., Ratner L. Conserved cysteine residues in the human immunodeficiency virus type 1 transmembrane envelope protein are essential for precursor envelope cleavage. J Virol. 1992 Feb;66(2):1207–1209. doi: 10.1128/jvi.66.2.1207-1209.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Earl P. L., Moss B., Doms R. W. Folding, interaction with GRP78-BiP, assembly, and transport of the human immunodeficiency virus type 1 envelope protein. J Virol. 1991 Apr;65(4):2047–2055. doi: 10.1128/jvi.65.4.2047-2055.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Elder J. H., Schnölzer M., Hasselkus-Light C. S., Henson M., Lerner D. A., Phillips T. R., Wagaman P. C., Kent S. B. Identification of proteolytic processing sites within the Gag and Pol polyproteins of feline immunodeficiency virus. J Virol. 1993 Apr;67(4):1869–1876. doi: 10.1128/jvi.67.4.1869-1876.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Fontenot J. D., Hoover E. A., Elder J. H., Montelaro R. C. Evaluation of feline immunodeficiency virus and feline leukemia virus transmembrane peptides for serological diagnosis. J Clin Microbiol. 1992 Jul;30(7):1885–1890. doi: 10.1128/jcm.30.7.1885-1890.1992. [DOI] [PMC free article] [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. Gnann J. W., Jr, Nelson J. A., Oldstone M. B. Fine mapping of an immunodominant domain in the transmembrane glycoprotein of human immunodeficiency virus. J Virol. 1987 Aug;61(8):2639–2641. doi: 10.1128/jvi.61.8.2639-2641.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Goff S., Traktman P., Baltimore D. Isolation and properties of Moloney murine leukemia virus mutants: use of a rapid assay for release of virion reverse transcriptase. J Virol. 1981 Apr;38(1):239–248. doi: 10.1128/jvi.38.1.239-248.1981. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Helseth E., Olshevsky U., Furman C., Sodroski J. Human immunodeficiency virus type 1 gp120 envelope glycoprotein regions important for association with the gp41 transmembrane glycoprotein. J Virol. 1991 Apr;65(4):2119–2123. doi: 10.1128/jvi.65.4.2119-2123.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Hunter E., Swanstrom R. Retrovirus envelope glycoproteins. Curr Top Microbiol Immunol. 1990;157:187–253. doi: 10.1007/978-3-642-75218-6_7. [DOI] [PubMed] [Google Scholar]
  18. Kunkel T. A. Rapid and efficient site-specific mutagenesis without phenotypic selection. Proc Natl Acad Sci U S A. 1985 Jan;82(2):488–492. doi: 10.1073/pnas.82.2.488. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Laemmli U. K. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970 Aug 15;227(5259):680–685. doi: 10.1038/227680a0. [DOI] [PubMed] [Google Scholar]
  20. Layne S. P., Merges M. J., Dembo M., Spouge J. L., Nara P. L. HIV requires multiple gp120 molecules for CD4-mediated infection. Nature. 1990 Jul 19;346(6281):277–279. doi: 10.1038/346277a0. [DOI] [PubMed] [Google Scholar]
  21. Lombardi S., Bendinelli M., Garzelli C. Detection of B epitopes on the p24 gag protein of feline immunodeficiency virus by monoclonal antibodies. AIDS Res Hum Retroviruses. 1993 Feb;9(2):141–146. doi: 10.1089/aid.1993.9.141. [DOI] [PubMed] [Google Scholar]
  22. Mahmood N., Hay A. J. An ELISA utilizing immobilised snowdrop lectin GNA for the detection of envelope glycoproteins of HIV and SIV. J Immunol Methods. 1992 Jul 6;151(1-2):9–13. doi: 10.1016/0022-1759(92)90101-x. [DOI] [PubMed] [Google Scholar]
  23. Norrby E., Biberfeld G., Chiodi F., von Gegerfeldt A., Nauclér A., Parks E., Lerner R. Discrimination between antibodies to HIV and to related retroviruses using site-directed serology. Nature. 1987 Sep 17;329(6136):248–250. doi: 10.1038/329248a0. [DOI] [PubMed] [Google Scholar]
  24. Oldstone M. B., Tishon A., Lewicki H., Dyson H. J., Feher V. A., Assa-Munt N., Wright P. E. Mapping the anatomy of the immunodominant domain of the human immunodeficiency virus gp41 transmembrane protein: peptide conformation analysis using monoclonal antibodies and proton nuclear magnetic resonance spectroscopy. J Virol. 1991 Apr;65(4):1727–1734. doi: 10.1128/jvi.65.4.1727-1734.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Osborne R., Rigby M., Siebelink K., Neil J. C., Jarrett O. Virus neutralization reveals antigenic variation among feline immunodeficiency virus isolates. J Gen Virol. 1994 Dec;75(Pt 12):3641–3645. doi: 10.1099/0022-1317-75-12-3641. [DOI] [PubMed] [Google Scholar]
  26. Pancino G., Chappey C., Saurin W., Sonigo P. B epitopes and selection pressures in feline immunodeficiency virus envelope glycoproteins. J Virol. 1993 Feb;67(2):664–672. doi: 10.1128/jvi.67.2.664-672.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Pancino G., Ellerbrok H., Sitbon M., Sonigo P. Conserved framework of envelope glycoproteins among lentiviruses. Curr Top Microbiol Immunol. 1994;188:77–105. doi: 10.1007/978-3-642-78536-8_5. [DOI] [PubMed] [Google Scholar]
  28. Pancino G., Fossati I., Chappey C., Castelot S., Hurtrel B., Moraillon A., Klatzmann D., Sonigo P. Structure and variations of feline immunodeficiency virus envelope glycoproteins. Virology. 1993 Feb;192(2):659–662. doi: 10.1006/viro.1993.1083. [DOI] [PubMed] [Google Scholar]
  29. Robinson W. E., Jr, Kawamura T., Lake D., Masuho Y., Mitchell W. M., Hersh E. M. Antibodies to the primary immunodominant domain of human immunodeficiency virus type 1 (HIV-1) glycoprotein gp41 enhance HIV-1 infection in vitro. J Virol. 1990 Nov;64(11):5301–5305. doi: 10.1128/jvi.64.11.5301-5305.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. 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]
  31. 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]
  32. Schulz T. F., Jameson B. A., Lopalco L., Siccardi A. G., Weiss R. A., Moore J. P. Conserved structural features in the interaction between retroviral surface and transmembrane glycoproteins? AIDS Res Hum Retroviruses. 1992 Sep;8(9):1571–1580. doi: 10.1089/aid.1992.8.1571. [DOI] [PubMed] [Google Scholar]
  33. 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]
  34. Stephens E. B., Monck E., Reppas K., Butfiloski E. J. Processing of the glycoprotein of feline immunodeficiency virus: effect of inhibitors of glycosylation. J Virol. 1991 Mar;65(3):1114–1123. doi: 10.1128/jvi.65.3.1114-1123.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Syu W. J., Lee W. R., Du B., Yu Q. C., Essex M., Lee T. H. Role of conserved gp41 cysteine residues in the processing of human immunodeficiency virus envelope precursor and viral infectivity. J Virol. 1991 Nov;65(11):6349–6352. doi: 10.1128/jvi.65.11.6349-6352.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. 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]
  37. Thomas E., Overbaugh J. Delayed cytopathicity of a feline leukemia virus variant is due to four mutations in the transmembrane protein gene. J Virol. 1993 Oct;67(10):5724–5732. doi: 10.1128/jvi.67.10.5724-5732.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Verschoor E. J., Hulskotte E. G., Ederveen J., Koolen M. J., Horzinek M. C., Rottier P. J. Post-translational processing of the feline immunodeficiency virus envelope precursor protein. Virology. 1993 Mar;193(1):433–438. doi: 10.1006/viro.1993.1140. [DOI] [PubMed] [Google Scholar]
  39. Willey R. L., Klimkait T., Frucht D. M., Bonifacino J. S., Martin M. A. Mutations within the human immunodeficiency virus type 1 gp160 envelope glycoprotein alter its intracellular transport and processing. Virology. 1991 Sep;184(1):319–329. doi: 10.1016/0042-6822(91)90848-6. [DOI] [PubMed] [Google Scholar]

Articles from Journal of Virology are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES