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. 1995 Apr;69(4):2708–2715. doi: 10.1128/jvi.69.4.2708-2715.1995

Sequence diversity of V1 and V2 domains of gp120 from human immunodeficiency virus type 1: lack of correlation with viral phenotype.

N Wang 1, T Zhu 1, D D Ho 1
PMCID: PMC188961  PMID: 7884929

Abstract

We analyzed by PCR and direct sequencing 57 viral sequences from 47 individuals infected with human immunodeficiency virus type 1, focussing on the V1 and V2 regions of gp120. There was extensive length polymorphism in the V1 region, which rendered sequence alignment difficult. The V2 hypervariable locus also displayed considerable length variations, whereas flanking regions were relatively conserved. Two-thirds of the amino acid residues in these flanking regions were highly conserved (> 80%), presumably reflecting their critical contribution to V2 structure or function. We also characterized the syncytium-inducing properties of the isolates from which we derived sequence information. There was no correlation between V1 or V2 sequences and the viral phenotype, contrary to a previous report (M. Groenink, R. A. M. Fouchier, S. Broersen, C. H. Baker, M. Koot, A. B. van't Wout, H. G. Huisman, F. Miedema, M. Tersmette, and H. Schuitemaker, Science 260:1513-1516, 1993). The sequence heterogeneity described in this study provides information to suggest that it would be most difficult to exploit the V1 and V2 domains for vaccine development.

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Selected References

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  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. 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]
  3. Bernstein H. B., Tucker S. P., Hunter E., Schutzbach J. S., Compans R. W. Human immunodeficiency virus type 1 envelope glycoprotein is modified by O-linked oligosaccharides. J Virol. 1994 Jan;68(1):463–468. doi: 10.1128/jvi.68.1.463-468.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Boyd M. T., Simpson G. R., Cann A. J., Johnson M. A., Weiss R. A. A single amino acid substitution in the V1 loop of human immunodeficiency virus type 1 gp120 alters cellular tropism. J Virol. 1993 Jun;67(6):3649–3652. doi: 10.1128/jvi.67.6.3649-3652.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Cheng-Mayer C., Seto D., Tateno M., Levy J. A. Biologic features of HIV-1 that correlate with virulence in the host. Science. 1988 Apr 1;240(4848):80–82. doi: 10.1126/science.2832945. [DOI] [PubMed] [Google Scholar]
  6. Connor R. I., Ho D. D. Human immunodeficiency virus type 1 variants with increased replicative capacity develop during the asymptomatic stage before disease progression. J Virol. 1994 Jul;68(7):4400–4408. doi: 10.1128/jvi.68.7.4400-4408.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Connor R. I., Mohri H., Cao Y., Ho D. D. Increased viral burden and cytopathicity correlate temporally with CD4+ T-lymphocyte decline and clinical progression in human immunodeficiency virus type 1-infected individuals. J Virol. 1993 Apr;67(4):1772–1777. doi: 10.1128/jvi.67.4.1772-1777.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Fouchier R. A., Groenink M., Kootstra N. A., Tersmette M., Huisman H. G., Miedema F., Schuitemaker H. Phenotype-associated sequence variation in the third variable domain of the human immunodeficiency virus type 1 gp120 molecule. J Virol. 1992 May;66(5):3183–3187. doi: 10.1128/jvi.66.5.3183-3187.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Freed E. O., Martin M. A. Evidence for a functional interaction between the V1/V2 and C4 domains of human immunodeficiency virus type 1 envelope glycoprotein gp120. J Virol. 1994 Apr;68(4):2503–2512. doi: 10.1128/jvi.68.4.2503-2512.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. 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]
  11. Gorny M. K., Moore J. P., Conley A. J., Karwowska S., Sodroski J., Williams C., Burda S., Boots L. J., Zolla-Pazner S. Human anti-V2 monoclonal antibody that neutralizes primary but not laboratory isolates of human immunodeficiency virus type 1. J Virol. 1994 Dec;68(12):8312–8320. doi: 10.1128/jvi.68.12.8312-8320.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Groenink M., Fouchier R. A., Broersen S., Baker C. H., Koot M., van't Wout A. B., Huisman H. G., Miedema F., Tersmette M., Schuitemaker H. Relation of phenotype evolution of HIV-1 to envelope V2 configuration. Science. 1993 Jun 4;260(5113):1513–1516. doi: 10.1126/science.8502996. [DOI] [PubMed] [Google Scholar]
  13. Groenink M., Fouchier R. A., de Goede R. E., de Wolf F., Gruters R. A., Cuypers H. T., Huisman H. G., Tersmette M. Phenotypic heterogeneity in a panel of infectious molecular human immunodeficiency virus type 1 clones derived from a single individual. J Virol. 1991 Apr;65(4):1968–1975. doi: 10.1128/jvi.65.4.1968-1975.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. 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]
  15. Hahn B. H., Shaw G. M., Taylor M. E., Redfield R. R., Markham P. D., Salahuddin S. Z., Wong-Staal F., Gallo R. C., Parks E. S., Parks W. P. Genetic variation in HTLV-III/LAV over time in patients with AIDS or at risk for AIDS. Science. 1986 Jun 20;232(4757):1548–1553. doi: 10.1126/science.3012778. [DOI] [PubMed] [Google Scholar]
  16. Hansen J. E., Clausen H., Hu S. L., Nielsen J. O., Olofsson S. An O-linked carbohydrate neutralization epitope of HIV-1 gp 120 is expressed by HIV-1 env gene recombinant vaccinia virus. Arch Virol. 1992;126(1-4):11–20. doi: 10.1007/BF01309680. [DOI] [PubMed] [Google Scholar]
  17. 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]
  18. Holmes E. C., Zhang L. Q., Simmonds P., Ludlam C. A., Brown A. J. Convergent and divergent sequence evolution in the surface envelope glycoprotein of human immunodeficiency virus type 1 within a single infected patient. Proc Natl Acad Sci U S A. 1992 Jun 1;89(11):4835–4839. doi: 10.1073/pnas.89.11.4835. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Javaherian K., Langlois A. J., McDanal C., Ross K. L., Eckler L. I., Jellis C. L., Profy A. T., Rusche J. R., Bolognesi D. P., Putney S. D. Principal neutralizing domain of the human immunodeficiency virus type 1 envelope protein. Proc Natl Acad Sci U S A. 1989 Sep;86(17):6768–6772. doi: 10.1073/pnas.86.17.6768. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. 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]
  21. Koito A., Harrowe G., Levy J. A., Cheng-Mayer C. Functional role of the V1/V2 region of human immunodeficiency virus type 1 envelope glycoprotein gp120 in infection of primary macrophages and soluble CD4 neutralization. J Virol. 1994 Apr;68(4):2253–2259. doi: 10.1128/jvi.68.4.2253-2259.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Koot M., Vos A. H., Keet R. P., de Goede R. E., Dercksen M. W., Terpstra F. G., Coutinho R. A., Miedema F., Tersmette M. HIV-1 biological phenotype in long-term infected individuals evaluated with an MT-2 cocultivation assay. AIDS. 1992 Jan;6(1):49–54. doi: 10.1097/00002030-199201000-00006. [DOI] [PubMed] [Google Scholar]
  23. Kuiken C. L., de Jong J. J., Baan E., Keulen W., Tersmette M., Goudsmit J. Evolution of the V3 envelope domain in proviral sequences and isolates of human immunodeficiency virus type 1 during transition of the viral biological phenotype. J Virol. 1992 Jul;66(7):4622–4627. doi: 10.1128/jvi.66.7.4622-4627.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Kusumi K., Conway B., Cunningham S., Berson A., Evans C., Iversen A. K., Colvin D., Gallo M. V., Coutre S., Shpaer E. G. Human immunodeficiency virus type 1 envelope gene structure and diversity in vivo and after cocultivation in vitro. J Virol. 1992 Feb;66(2):875–885. doi: 10.1128/jvi.66.2.875-885.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Lamers S. L., Sleasman J. W., She J. X., Barrie K. A., Pomeroy S. M., Barrett D. J., Goodenow M. M. Independent variation and positive selection in env V1 and V2 domains within maternal-infant strains of human immunodeficiency virus type 1 in vivo. J Virol. 1993 Jul;67(7):3951–3960. doi: 10.1128/jvi.67.7.3951-3960.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. 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]
  27. Liu Z. Q., Wood C., Levy J. A., Cheng-Mayer C. The viral envelope gene is involved in macrophage tropism of a human immunodeficiency virus type 1 strain isolated from brain tissue. J Virol. 1990 Dec;64(12):6148–6153. doi: 10.1128/jvi.64.12.6148-6153.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Meyerhans A., Cheynier R., Albert J., Seth M., Kwok S., Sninsky J., Morfeldt-Månson L., Asjö B., Wain-Hobson S. Temporal fluctuations in HIV quasispecies in vivo are not reflected by sequential HIV isolations. Cell. 1989 Sep 8;58(5):901–910. doi: 10.1016/0092-8674(89)90942-2. [DOI] [PubMed] [Google Scholar]
  29. Milich L., Margolin B., Swanstrom R. V3 loop of the human immunodeficiency virus type 1 Env protein: interpreting sequence variability. J Virol. 1993 Sep;67(9):5623–5634. doi: 10.1128/jvi.67.9.5623-5634.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. 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]
  31. Moore J. P., McCutchan F. E., Poon S. W., Mascola J., Liu J., Cao Y., Ho D. D. Exploration of antigenic variation in gp120 from clades A through F of human immunodeficiency virus type 1 by using monoclonal antibodies. J Virol. 1994 Dec;68(12):8350–8364. doi: 10.1128/jvi.68.12.8350-8364.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. 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]
  33. O'Brien W. A., Koyanagi Y., Namazie A., Zhao J. Q., Diagne A., Idler K., Zack J. A., Chen I. S. HIV-1 tropism for mononuclear phagocytes can be determined by regions of gp120 outside the CD4-binding domain. Nature. 1990 Nov 1;348(6296):69–73. doi: 10.1038/348069a0. [DOI] [PubMed] [Google Scholar]
  34. Overbaugh J., Rudensey L. M. Alterations in potential sites for glycosylation predominate during evolution of the simian immunodeficiency virus envelope gene in macaques. J Virol. 1992 Oct;66(10):5937–5948. doi: 10.1128/jvi.66.10.5937-5948.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Pedroza Martins L., Chenciner N., Wain-Hobson S. Complex intrapatient sequence variation in the V1 and V2 hypervariable regions of the HIV-1 gp 120 envelope sequence. Virology. 1992 Dec;191(2):837–845. doi: 10.1016/0042-6822(92)90259-r. [DOI] [PubMed] [Google Scholar]
  36. Pincus S. H., Messer K. G., Nara P. L., Blattner W. A., Colclough G., Reitz M. Temporal analysis of the antibody response to HIV envelope protein in HIV-infected laboratory workers. J Clin Invest. 1994 Jun;93(6):2505–2513. doi: 10.1172/JCI117260. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Roos M. T., Lange J. M., de Goede R. E., Coutinho R. A., Schellekens P. T., Miedema F., Tersmette M. Viral phenotype and immune response in primary human immunodeficiency virus type 1 infection. J Infect Dis. 1992 Mar;165(3):427–432. doi: 10.1093/infdis/165.3.427. [DOI] [PubMed] [Google Scholar]
  38. Saag M. S., Hahn B. H., Gibbons J., Li Y., Parks E. S., Parks W. P., Shaw G. M. Extensive variation of human immunodeficiency virus type-1 in vivo. Nature. 1988 Aug 4;334(6181):440–444. doi: 10.1038/334440a0. [DOI] [PubMed] [Google Scholar]
  39. Schlienger K., Montefiori D. C., Mancini M., Rivière Y., Tiollais P., Michel M. L. Vaccine-induced neutralizing antibodies directed in part to the simian immunodeficiency virus (SIV) V2 domain were unable to protect rhesus monkeys from SIV experimental challenge. J Virol. 1994 Oct;68(10):6578–6588. doi: 10.1128/jvi.68.10.6578-6588.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Simmonds P., Zhang L. Q., McOmish F., Balfe P., Ludlam C. A., Brown A. J. Discontinuous sequence change of human immunodeficiency virus (HIV) type 1 env sequences in plasma viral and lymphocyte-associated proviral populations in vivo: implications for models of HIV pathogenesis. J Virol. 1991 Nov;65(11):6266–6276. doi: 10.1128/jvi.65.11.6266-6276.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. 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]
  42. 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]
  43. Tersmette M., Gruters R. A., de Wolf F., de Goede R. E., Lange J. M., Schellekens P. T., Goudsmit J., Huisman H. G., Miedema F. Evidence for a role of virulent human immunodeficiency virus (HIV) variants in the pathogenesis of acquired immunodeficiency syndrome: studies on sequential HIV isolates. J Virol. 1989 May;63(5):2118–2125. doi: 10.1128/jvi.63.5.2118-2125.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. Tersmette M., Lange J. M., de Goede R. E., de Wolf F., Eeftink-Schattenkerk J. K., Schellekens P. T., Coutinho R. A., Huisman J. G., Goudsmit J., Miedema F. Association between biological properties of human immunodeficiency virus variants and risk for AIDS and AIDS mortality. Lancet. 1989 May 6;1(8645):983–985. doi: 10.1016/s0140-6736(89)92628-7. [DOI] [PubMed] [Google Scholar]
  45. Tersmette M., de Goede R. E., Al B. J., Winkel I. N., Gruters R. A., Cuypers H. T., Huisman H. G., Miedema F. Differential syncytium-inducing capacity of human immunodeficiency virus isolates: frequent detection of syncytium-inducing isolates in patients with acquired immunodeficiency syndrome (AIDS) and AIDS-related complex. J Virol. 1988 Jun;62(6):2026–2032. doi: 10.1128/jvi.62.6.2026-2032.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  46. Warrier S. V., Pinter A., Honnen W. J., Girard M., Muchmore E., Tilley S. A. A novel, glycan-dependent epitope in the V2 domain of human immunodeficiency virus type 1 gp120 is recognized by a highly potent, neutralizing chimpanzee monoclonal antibody. J Virol. 1994 Jul;68(7):4636–4642. doi: 10.1128/jvi.68.7.4636-4642.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  47. Westervelt P., Trowbridge D. B., Epstein L. G., Blumberg B. M., Li Y., Hahn B. H., Shaw G. M., Price R. W., Ratner L. Macrophage tropism determinants of human immunodeficiency virus type 1 in vivo. J Virol. 1992 Apr;66(4):2577–2582. doi: 10.1128/jvi.66.4.2577-2582.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  48. Willey R. L., Rutledge R. A., Dias S., Folks T., Theodore T., Buckler C. E., Martin M. A. Identification of conserved and divergent domains within the envelope gene of the acquired immunodeficiency syndrome retrovirus. Proc Natl Acad Sci U S A. 1986 Jul;83(14):5038–5042. doi: 10.1073/pnas.83.14.5038. [DOI] [PMC free article] [PubMed] [Google Scholar]
  49. 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]
  50. Yoshiyama H., Mo H., Moore J. P., Ho D. D. Characterization of mutants of human immunodeficiency virus type 1 that have escaped neutralization by a monoclonal antibody to the gp120 V2 loop. J Virol. 1994 Feb;68(2):974–978. doi: 10.1128/jvi.68.2.974-978.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  51. Zhu T., Mo H., Wang N., Nam D. S., Cao Y., Koup R. A., Ho D. D. Genotypic and phenotypic characterization of HIV-1 patients with primary infection. Science. 1993 Aug 27;261(5125):1179–1181. doi: 10.1126/science.8356453. [DOI] [PubMed] [Google Scholar]
  52. Zhu T., Wang N., Carr A., Wolinsky S., Ho D. D. Evidence for coinfection by multiple strains of human immunodeficiency virus type 1 subtype B in an acute seroconvertor. J Virol. 1995 Feb;69(2):1324–1327. doi: 10.1128/jvi.69.2.1324-1327.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]

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