Skip to main content
NCBI home page
Journal of Virology logoLink to Journal of Virology
. 1995 Jan;69(1):538–542. doi: 10.1128/jvi.69.1.538-542.1995

The highly conserved aspartic acid residue between hypervariable regions 1 and 2 of human immunodeficiency virus type 1 gp120 is important for early stages of virus replication.

W K Wang 1, M Essex 1, T H Lee 1
PMCID: PMC188606  PMID: 7983752

Abstract

Between hypervariable regions V1 and V2 of human immunodeficiency virus type 1 (HIV-1) gp120 lies a cluster of relatively conserved residues. The contribution of nine charged residues in this region to virus infectivity was evaluated by single-amino-acid substitutions in an infectious provirus clone. Three of the HIV-1 mutants studied had slower growth kinetics than the wild-type virus. The delay was most pronounced in a mutant with an alanine substituted for an aspartic acid residue at position 180. This aspartic acid is conserved by all HIV-1 isolates with known nucleotide sequences. Substitutions with three other residues at this position, including a negatively charged glutamic acid, all affected virus infectivity. The defect identified in these mutants suggests that this aspartic acid residue is involved in the early stages of HIV-1 replication.

Full Text

The Full Text of this article is available as a PDF (268.3 KB).

Selected References

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

  1. Andeweg A. C., Leeflang P., Osterhaus A. D., Bosch M. L. Both the V2 and V3 regions of the human immunodeficiency virus type 1 surface glycoprotein functionally interact with other envelope regions in syncytium formation. J Virol. 1993 Jun;67(6):3232–3239. doi: 10.1128/jvi.67.6.3232-3239.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Barré-Sinoussi F., Chermann J. C., Rey F., Nugeyre M. T., Chamaret S., Gruest J., Dauguet C., Axler-Blin C., Vézinet-Brun F., Rouzioux C. Isolation of a T-lymphotropic retrovirus from a patient at risk for acquired immune deficiency syndrome (AIDS). Science. 1983 May 20;220(4599):868–871. doi: 10.1126/science.6189183. [DOI] [PubMed] [Google Scholar]
  3. Benn S., Rutledge R., Folks T., Gold J., Baker L., McCormick J., Feorino P., Piot P., Quinn T., Martin M. Genomic heterogeneity of AIDS retroviral isolates from North America and Zaire. Science. 1985 Nov 22;230(4728):949–951. doi: 10.1126/science.2997922. [DOI] [PubMed] [Google Scholar]
  4. Cordonnier A., Montagnier L., Emerman M. Single amino-acid changes in HIV envelope affect viral tropism and receptor binding. Nature. 1989 Aug 17;340(6234):571–574. doi: 10.1038/340571a0. [DOI] [PubMed] [Google Scholar]
  5. Dalgleish A. G., Beverley P. C., Clapham P. R., Crawford D. H., Greaves M. F., Weiss R. A. The CD4 (T4) antigen is an essential component of the receptor for the AIDS retrovirus. Nature. 1984 Dec 20;312(5996):763–767. doi: 10.1038/312763a0. [DOI] [PubMed] [Google Scholar]
  6. Fisher A. G., Collalti E., Ratner L., Gallo R. C., Wong-Staal F. A molecular clone of HTLV-III with biological activity. Nature. 1985 Jul 18;316(6025):262–265. doi: 10.1038/316262a0. [DOI] [PubMed] [Google Scholar]
  7. Fung M. S., Sun C. R., Gordon W. L., Liou R. S., Chang T. W., Sun W. N., Daar E. S., Ho D. D. Identification and characterization of a neutralization site within the second variable region of human immunodeficiency virus type 1 gp120. J Virol. 1992 Feb;66(2):848–856. doi: 10.1128/jvi.66.2.848-856.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Gallo R. C., Salahuddin S. Z., Popovic M., Shearer G. M., Kaplan M., Haynes B. F., Palker T. J., Redfield R., Oleske J., Safai B. Frequent detection and isolation of cytopathic retroviruses (HTLV-III) from patients with AIDS and at risk for AIDS. Science. 1984 May 4;224(4648):500–503. doi: 10.1126/science.6200936. [DOI] [PubMed] [Google Scholar]
  9. Hahn B. H., Gonda M. A., Shaw G. M., Popovic M., Hoxie J. A., Gallo R. C., Wong-Staal F. Genomic diversity of the acquired immune deficiency syndrome virus HTLV-III: different viruses exhibit greatest divergence in their envelope genes. Proc Natl Acad Sci U S A. 1985 Jul;82(14):4813–4817. doi: 10.1073/pnas.82.14.4813. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Helseth E., Kowalski M., Gabuzda D., Olshevsky U., Haseltine W., Sodroski J. Rapid complementation assays measuring replicative potential of human immunodeficiency virus type 1 envelope glycoprotein mutants. J Virol. 1990 May;64(5):2416–2420. doi: 10.1128/jvi.64.5.2416-2420.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Ho D. D., Fung M. S., Cao Y. Z., Li X. L., Sun C., Chang T. W., Sun N. C. Another discontinuous epitope on glycoprotein gp120 that is important in human immunodeficiency virus type 1 neutralization is identified by a monoclonal antibody. Proc Natl Acad Sci U S A. 1991 Oct 15;88(20):8949–8952. doi: 10.1073/pnas.88.20.8949. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Kayman S. C., Wu Z., Revesz K., Chen H., Kopelman R., Pinter A. Presentation of native epitopes in the V1/V2 and V3 regions of human immunodeficiency virus type 1 gp120 by fusion glycoproteins containing isolated gp120 domains. J Virol. 1994 Jan;68(1):400–410. doi: 10.1128/jvi.68.1.400-410.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Klatzmann D., Champagne E., Chamaret S., Gruest J., Guetard D., Hercend T., Gluckman J. C., Montagnier L. T-lymphocyte T4 molecule behaves as the receptor for human retrovirus LAV. Nature. 1984 Dec 20;312(5996):767–768. doi: 10.1038/312767a0. [DOI] [PubMed] [Google Scholar]
  14. Kornfeld H., Riedel N., Viglianti G. A., Hirsch V., Mullins J. I. Cloning of HTLV-4 and its relation to simian and human immunodeficiency viruses. Nature. 1987 Apr 9;326(6113):610–613. doi: 10.1038/326610a0. [DOI] [PubMed] [Google Scholar]
  15. Kowalski M., Potz J., Basiripour L., Dorfman T., Goh W. C., Terwilliger E., Dayton A., Rosen C., Haseltine W., Sodroski J. Functional regions of the envelope glycoprotein of human immunodeficiency virus type 1. Science. 1987 Sep 11;237(4820):1351–1355. doi: 10.1126/science.3629244. [DOI] [PubMed] [Google Scholar]
  16. 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]
  17. Lasky L. A., Nakamura G., Smith D. H., Fennie C., Shimasaki C., Patzer E., Berman P., Gregory T., Capon D. J. Delineation of a region of the human immunodeficiency virus type 1 gp120 glycoprotein critical for interaction with the CD4 receptor. Cell. 1987 Sep 11;50(6):975–985. doi: 10.1016/0092-8674(87)90524-1. [DOI] [PubMed] [Google Scholar]
  18. Lee W. R., Yu X. F., Syu W. J., Essex M., Lee T. H. Mutational analysis of conserved N-linked glycosylation sites of human immunodeficiency virus type 1 gp41. J Virol. 1992 Mar;66(3):1799–1803. doi: 10.1128/jvi.66.3.1799-1803.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Leonard C. K., Spellman M. W., Riddle L., Harris R. J., Thomas J. N., Gregory T. J. Assignment of intrachain disulfide bonds and characterization of potential glycosylation sites of the type 1 recombinant human immunodeficiency virus envelope glycoprotein (gp120) expressed in Chinese hamster ovary cells. J Biol Chem. 1990 Jun 25;265(18):10373–10382. [PubMed] [Google Scholar]
  20. Linsley P. S., Ledbetter J. A., Kinney-Thomas E., Hu S. L. Effects of anti-gp120 monoclonal antibodies on CD4 receptor binding by the env protein of human immunodeficiency virus type 1. J Virol. 1988 Oct;62(10):3695–3702. doi: 10.1128/jvi.62.10.3695-3702.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. McDougal J. S., Kennedy M. S., Sligh J. M., Cort S. P., Mawle A., Nicholson J. K. Binding of HTLV-III/LAV to T4+ T cells by a complex of the 110K viral protein and the T4 molecule. Science. 1986 Jan 24;231(4736):382–385. doi: 10.1126/science.3001934. [DOI] [PubMed] [Google Scholar]
  22. McDougal J. S., Nicholson J. K., Cross G. D., Cort S. P., Kennedy M. S., Mawle A. C. Binding of the human retrovirus HTLV-III/LAV/ARV/HIV to the CD4 (T4) molecule: conformation dependence, epitope mapping, antibody inhibition, and potential for idiotypic mimicry. J Immunol. 1986 Nov 1;137(9):2937–2944. [PubMed] [Google Scholar]
  23. 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]
  24. Moore J. P., Sattentau Q. J., Yoshiyama H., Thali M., Charles M., Sullivan N., Poon S. W., Fung M. S., Traincard F., Pinkus M. Probing the structure of the V2 domain of human immunodeficiency virus type 1 surface glycoprotein gp120 with a panel of eight monoclonal antibodies: human immune response to the V1 and V2 domains. J Virol. 1993 Oct;67(10):6136–6151. doi: 10.1128/jvi.67.10.6136-6151.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Olshevsky U., Helseth E., Furman C., Li J., Haseltine W., Sodroski J. Identification of individual human immunodeficiency virus type 1 gp120 amino acids important for CD4 receptor binding. J Virol. 1990 Dec;64(12):5701–5707. doi: 10.1128/jvi.64.12.5701-5707.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Pollard S. R., Rosa M. D., Rosa J. J., Wiley D. C. Truncated variants of gp120 bind CD4 with high affinity and suggest a minimum CD4 binding region. EMBO J. 1992 Feb;11(2):585–591. doi: 10.1002/j.1460-2075.1992.tb05090.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Popovic M., Sarngadharan M. G., Read E., Gallo R. C. Detection, isolation, and continuous production of cytopathic retroviruses (HTLV-III) from patients with AIDS and pre-AIDS. Science. 1984 May 4;224(4648):497–500. doi: 10.1126/science.6200935. [DOI] [PubMed] [Google Scholar]
  28. Ratner L., Gallo R. C., Wong-Staal F. HTLV-III, LAV, ARV are variants of same AIDS virus. Nature. 1985 Feb 21;313(6004):636–637. doi: 10.1038/313636c0. [DOI] [PubMed] [Google Scholar]
  29. Sarngadharan M. G., Popovic M., Bruch L., Schüpbach J., Gallo R. C. Antibodies reactive with human T-lymphotropic retroviruses (HTLV-III) in the serum of patients with AIDS. Science. 1984 May 4;224(4648):506–508. doi: 10.1126/science.6324345. [DOI] [PubMed] [Google Scholar]
  30. Shaw G. M., Hahn B. H., Arya S. K., Groopman J. E., Gallo R. C., Wong-Staal F. Molecular characterization of human T-cell leukemia (lymphotropic) virus type III in the acquired immune deficiency syndrome. Science. 1984 Dec 7;226(4679):1165–1171. doi: 10.1126/science.6095449. [DOI] [PubMed] [Google Scholar]
  31. Sullivan N., Thali M., Furman C., Ho D. D., Sodroski J. Effect of amino acid changes in the V1/V2 region of the human immunodeficiency virus type 1 gp120 glycoprotein on subunit association, syncytium formation, and recognition by a neutralizing antibody. J Virol. 1993 Jun;67(6):3674–3679. doi: 10.1128/jvi.67.6.3674-3679.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Syu W. J., Huang J. H., Essex M., Lee T. H. The N-terminal region of the human immunodeficiency virus envelope glycoprotein gp120 contains potential binding sites for CD4. Proc Natl Acad Sci U S A. 1990 May;87(10):3695–3699. doi: 10.1073/pnas.87.10.3695. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Thali M., Furman C., Ho D. D., Robinson J., Tilley S., Pinter A., Sodroski J. Discontinuous, conserved neutralization epitopes overlapping the CD4-binding region of human immunodeficiency virus type 1 gp120 envelope glycoprotein. J Virol. 1992 Sep;66(9):5635–5641. doi: 10.1128/jvi.66.9.5635-5641.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Thali M., Olshevsky U., Furman C., Gabuzda D., Posner M., Sodroski J. Characterization of a discontinuous human immunodeficiency virus type 1 gp120 epitope recognized by a broadly reactive neutralizing human monoclonal antibody. J Virol. 1991 Nov;65(11):6188–6193. doi: 10.1128/jvi.65.11.6188-6193.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Wong-Staal F., Shaw G. M., Hahn B. H., Salahuddin S. Z., Popovic M., Markham P., Redfield R., Gallo R. C. Genomic diversity of human T-lymphotropic virus type III (HTLV-III). Science. 1985 Aug 23;229(4715):759–762. doi: 10.1126/science.2992084. [DOI] [PubMed] [Google Scholar]
  36. Wyatt R., Sullivan N., Thali M., Repke H., Ho D., Robinson J., Posner M., Sodroski J. Functional and immunologic characterization of human immunodeficiency virus type 1 envelope glycoproteins containing deletions of the major variable regions. J Virol. 1993 Aug;67(8):4557–4565. doi: 10.1128/jvi.67.8.4557-4565.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Yu X. F., Ito S., Essex M., Lee T. H. A naturally immunogenic virion-associated protein specific for HIV-2 and SIV. Nature. 1988 Sep 15;335(6187):262–265. doi: 10.1038/335262a0. [DOI] [PubMed] [Google Scholar]
  38. Yuan X., Yu X., Lee T. H., Essex M. Mutations in the N-terminal region of human immunodeficiency virus type 1 matrix protein block intracellular transport of the Gag precursor. J Virol. 1993 Nov;67(11):6387–6394. doi: 10.1128/jvi.67.11.6387-6394.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]

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

RESOURCES