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Journal of Virology logoLink to Journal of Virology
. 1993 Oct;67(10):6136–6151. doi: 10.1128/jvi.67.10.6136-6151.1993

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 P Moore 1, Q J Sattentau 1, H Yoshiyama 1, M Thali 1, M Charles 1, N Sullivan 1, S W Poon 1, M S Fung 1, F Traincard 1, M Pinkus 1, et al.
PMCID: PMC238036  PMID: 7690418

Abstract

We have analyzed a panel of eight murine monoclonal antibodies (MAbs) that depend on the V2 domain for binding to human immunodeficiency virus type 1 (HIV-1) gp120. Each MAb is sensitive to amino acid changes within V2, and some are affected by substitutions elsewhere. With one exception, the MAbs were not reactive with peptides from the V2 region, or only poorly so. Hence their ability to bind recombinant strain IIIB gp120 depended on the preservation of native structure. Three MAbs cross-reacted with strain RF gp120, but only one cross-reacted with MN gp120, and none bound SF-2 gp120. Four MAbs neutralized HIV-1 IIIB with various potencies, and the one able to bind MN gp120 neutralized that virus. Peptide serology indicated that antibodies cross-reactive with the HxB2 V1 and V2 regions are rarely present in HIV-1-positive sera, but the relatively conserved segment between the V1 and V2 loops was recognized by antibodies in a significant fraction of sera. Antibodies able to block the binding of V2 MAbs to IIIB or MN gp120 rarely exist in sera from HIV-1-infected humans; more common in these sera are antibodies that enhance the binding of V2 MAbs to gp120. This enhancement effect of HIV-1-positive sera can be mimicked by several human MAbs to different discontinuous gp120 epitopes. Soluble CD4 enhanced binding of one V2 MAb to oligomeric gp120 but not to monomeric gp120, perhaps by inducing conformational changes in the oligomer.

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Selected References

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  1. Benichou S., Legrand R., Nakagawa N., Faure T., Traincard F., Vogt G., Dormont D., Tiollais P., Kieny M. P., Madaule P. Identification of a neutralizing domain in the external envelope glycoprotein of simian immunodeficiency virus. AIDS Res Hum Retroviruses. 1992 Jun;8(6):1165–1170. doi: 10.1089/aid.1992.8.1165. [DOI] [PubMed] [Google Scholar]
  2. 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]
  3. Clements G. J., Price-Jones M. J., Stephens P. E., Sutton C., Schulz T. F., Clapham P. R., McKeating J. A., McClure M. O., Thomson S., Marsh M. The V3 loops of the HIV-1 and HIV-2 surface glycoproteins contain proteolytic cleavage sites: a possible function in viral fusion? AIDS Res Hum Retroviruses. 1991 Jan;7(1):3–16. doi: 10.1089/aid.1991.7.3. [DOI] [PubMed] [Google Scholar]
  4. Coffin J. M. Genetic variation in AIDS viruses. Cell. 1986 Jul 4;46(1):1–4. doi: 10.1016/0092-8674(86)90851-2. [DOI] [PubMed] [Google Scholar]
  5. D'Souza M. P., Kent K. A., Thiriart C., Collignon C., Milman G. International collaboration comparing neutralization and binding assays for monoclonal antibodies to simian immunodeficiency virus. AIDS Res Hum Retroviruses. 1993 May;9(5):415–422. doi: 10.1089/aid.1993.9.415. [DOI] [PubMed] [Google Scholar]
  6. Fisher R. A., Bertonis J. M., Meier W., Johnson V. A., Costopoulos D. S., Liu T., Tizard R., Walker B. D., Hirsch M. S., Schooley R. T. HIV infection is blocked in vitro by recombinant soluble CD4. Nature. 1988 Jan 7;331(6151):76–78. doi: 10.1038/331076a0. [DOI] [PubMed] [Google Scholar]
  7. Freed E. O., Myers D. J., Risser R. Identification of the principal neutralizing determinant of human immunodeficiency virus type 1 as a fusion domain. J Virol. 1991 Jan;65(1):190–194. doi: 10.1128/jvi.65.1.190-194.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Gorny M. K., Conley A. J., Karwowska S., Buchbinder A., Xu J. Y., Emini E. A., Koenig S., Zolla-Pazner S. Neutralization of diverse human immunodeficiency virus type 1 variants by an anti-V3 human monoclonal antibody. J Virol. 1992 Dec;66(12):7538–7542. doi: 10.1128/jvi.66.12.7538-7542.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Haigwood N. L., Shuster J. R., Moore G. K., Lee H., Skiles P. V., Higgins K. W., Barr P. J., George-Nascimento C., Steimer K. S. Importance of hypervariable regions of HIV-1 gp120 in the generation of virus neutralizing antibodies. AIDS Res Hum Retroviruses. 1990 Jul;6(7):855–869. doi: 10.1089/aid.1990.6.855. [DOI] [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. 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]
  12. 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]
  13. Ho D. D., McKeating J. A., Li X. L., Moudgil T., Daar E. S., Sun N. C., Robinson J. E. Conformational epitope on gp120 important in CD4 binding and human immunodeficiency virus type 1 neutralization identified by a human monoclonal antibody. J Virol. 1991 Jan;65(1):489–493. doi: 10.1128/jvi.65.1.489-493.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Ivanoff L. A., Looney D. J., McDanal C., Morris J. F., Wong-Staal F., Langlois A. J., Petteway S. R., Jr, Matthews T. J. Alteration of HIV-1 infectivity and neutralization by a single amino acid replacement in the V3 loop domain. AIDS Res Hum Retroviruses. 1991 Jul;7(7):595–603. doi: 10.1089/aid.1991.7.595. [DOI] [PubMed] [Google Scholar]
  15. Javaherian K., Langlois A. J., Schmidt S., Kaufmann M., Cates N., Langedijk J. P., Meloen R. H., Desrosiers R. C., Burns D. P., Bolognesi D. P. The principal neutralization determinant of simian immunodeficiency virus differs from that of human immunodeficiency virus type 1. Proc Natl Acad Sci U S A. 1992 Feb 15;89(4):1418–1422. doi: 10.1073/pnas.89.4.1418. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Katz R. A., Skalka A. M. Generation of diversity in retroviruses. Annu Rev Genet. 1990;24:409–445. doi: 10.1146/annurev.ge.24.120190.002205. [DOI] [PubMed] [Google Scholar]
  17. Kent K. A., Rud E., Corcoran T., Powell C., Thiriart C., Collignon C., Stott E. J. Identification of two neutralizing and 8 non-neutralizing epitopes on simian immunodeficiency virus envelope using monoclonal antibodies. AIDS Res Hum Retroviruses. 1992 Jun;8(6):1147–1151. doi: 10.1089/aid.1992.8.1147. [DOI] [PubMed] [Google Scholar]
  18. 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]
  19. LaRosa G. J., Davide J. P., Weinhold K., Waterbury J. A., Profy A. T., Lewis J. A., Langlois A. J., Dreesman G. R., Boswell R. N., Shadduck P. Conserved sequence and structural elements in the HIV-1 principal neutralizing determinant. Science. 1990 Aug 24;249(4971):932–935. doi: 10.1126/science.2392685. [DOI] [PubMed] [Google Scholar]
  20. 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]
  21. 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]
  22. McKeating J. A., Shotton C., Cordell J., Graham S., Balfe P., Sullivan N., Charles M., Page M., Bolmstedt A., Olofsson S. Characterization of neutralizing monoclonal antibodies to linear and conformation-dependent epitopes within the first and second variable domains of human immunodeficiency virus type 1 gp120. J Virol. 1993 Aug;67(8):4932–4944. doi: 10.1128/jvi.67.8.4932-4944.1993. [DOI] [PMC free article] [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., Ho D. D. Antibodies to discontinuous or conformationally sensitive epitopes on the gp120 glycoprotein of human immunodeficiency virus type 1 are highly prevalent in sera of infected humans. J Virol. 1993 Feb;67(2):863–875. doi: 10.1128/jvi.67.2.863-875.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Moore J. P., McKeating J. A., Jones I. M., Stephens P. E., Clements G., Thomson S., Weiss R. A. Characterization of recombinant gp120 and gp160 from HIV-1: binding to monoclonal antibodies and soluble CD4. AIDS. 1990 Apr;4(4):307–315. doi: 10.1097/00002030-199004000-00004. [DOI] [PubMed] [Google Scholar]
  26. Moore J. P., Nara P. L. The role of the V3 loop of gp120 in HIV infection. AIDS. 1991;5 (Suppl 2):S21–S33. doi: 10.1097/00002030-199101001-00004. [DOI] [PubMed] [Google Scholar]
  27. Moore J. P., Sattentau Q. J., Klasse P. J., Burkly L. C. A monoclonal antibody to CD4 domain 2 blocks soluble CD4-induced conformational changes in the envelope glycoproteins of human immunodeficiency virus type 1 (HIV-1) and HIV-1 infection of CD4+ cells. J Virol. 1992 Aug;66(8):4784–4793. doi: 10.1128/jvi.66.8.4784-4793.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Moore J. P. Simple methods for monitoring HIV-1 and HIV-2 gp120 binding to soluble CD4 by enzyme-linked immunosorbent assay: HIV-2 has a 25-fold lower affinity than HIV-1 for soluble CD4. AIDS. 1990 Apr;4(4):297–305. doi: 10.1097/00002030-199004000-00003. [DOI] [PubMed] [Google Scholar]
  29. Moore J. P., Thali M., Jameson B. A., Vignaux F., Lewis G. K., Poon S. W., Charles M., Fung M. S., Sun B., Durda P. J. Immunochemical analysis of the gp120 surface glycoprotein of human immunodeficiency virus type 1: probing the structure of the C4 and V4 domains and the interaction of the C4 domain with the V3 loop. J Virol. 1993 Aug;67(8):4785–4796. doi: 10.1128/jvi.67.8.4785-4796.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Moore J. P. The reactivities of HIV-1+ human sera with solid-phase V3 loop peptides can be poor predictors of their reactivities with V3 loops on native gp120 molecules. AIDS Res Hum Retroviruses. 1993 Mar;9(3):209–219. doi: 10.1089/aid.1993.9.209. [DOI] [PubMed] [Google Scholar]
  31. 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]
  32. 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]
  33. Overbaugh J., Rudensey L. M., Papenhausen M. D., Benveniste R. E., Morton W. R. Variation in simian immunodeficiency virus env is confined to V1 and V4 during progression to simian AIDS. J Virol. 1991 Dec;65(12):7025–7031. doi: 10.1128/jvi.65.12.7025-7031.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. 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]
  35. 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]
  36. Sakai H., Sakuragi S., Sakuragi J., Kawamura M., Shibata R., Adachi A. Sequences responsible for efficient replication of simian immunodeficiency virus SIVMND in cells of the monocyte/macrophage lineage. J Gen Virol. 1992 Nov;73(Pt 11):2989–2993. doi: 10.1099/0022-1317-73-11-2989. [DOI] [PubMed] [Google Scholar]
  37. Sattentau Q. J., Moore J. P. Conformational changes induced in the human immunodeficiency virus envelope glycoprotein by soluble CD4 binding. J Exp Med. 1991 Aug 1;174(2):407–415. doi: 10.1084/jem.174.2.407. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. 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]
  39. Steimer K. S., Scandella C. J., Skiles P. V., Haigwood N. L. Neutralization of divergent HIV-1 isolates by conformation-dependent human antibodies to Gp120. Science. 1991 Oct 4;254(5028):105–108. doi: 10.1126/science.1718036. [DOI] [PubMed] [Google Scholar]
  40. 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]
  41. Sun N. C., Ho D. D., Sun C. R., Liou R. S., Gordon W., Fung M. S., Li X. L., Ting R. C., Lee T. H., Chang N. T. Generation and characterization of monoclonal antibodies to the putative CD4-binding domain of human immunodeficiency virus type 1 gp120. J Virol. 1989 Sep;63(9):3579–3585. doi: 10.1128/jvi.63.9.3579-3585.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. 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]
  43. Thali M., Moore J. P., Furman C., Charles M., Ho D. D., Robinson J., Sodroski J. Characterization of conserved human immunodeficiency virus type 1 gp120 neutralization epitopes exposed upon gp120-CD4 binding. J Virol. 1993 Jul;67(7):3978–3988. doi: 10.1128/jvi.67.7.3978-3988.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. 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]
  45. Thomas E. K., Weber J. N., McClure J., Clapham P. R., Singhal M. C., Shriver M. K., Weiss R. A. Neutralizing monoclonal antibodies to the AIDS virus. AIDS. 1988 Feb;2(1):25–29. doi: 10.1097/00002030-198802000-00004. [DOI] [PubMed] [Google Scholar]
  46. Tilley S. A., Honnen W. J., Racho M. E., Chou T. C., Pinter A. Synergistic neutralization of HIV-1 by human monoclonal antibodies against the V3 loop and the CD4-binding site of gp120. AIDS Res Hum Retroviruses. 1992 Apr;8(4):461–467. doi: 10.1089/aid.1992.8.461. [DOI] [PubMed] [Google Scholar]
  47. Weiss S. H., Goedert J. J., Gartner S., Popovic M., Waters D., Markham P., di Marzo Veronese F., Gail M. H., Barkley W. E., Gibbons J. Risk of human immunodeficiency virus (HIV-1) infection among laboratory workers. Science. 1988 Jan 1;239(4835):68–71. doi: 10.1126/science.3336776. [DOI] [PubMed] [Google Scholar]
  48. Westervelt P., Gendelman H. E., Ratner L. Identification of a determinant within the human immunodeficiency virus 1 surface envelope glycoprotein critical for productive infection of primary monocytes. Proc Natl Acad Sci U S A. 1991 Apr 15;88(8):3097–3101. doi: 10.1073/pnas.88.8.3097. [DOI] [PMC free article] [PubMed] [Google Scholar]
  49. Wyatt R., Thali M., Tilley S., Pinter A., Posner M., Ho D., Robinson J., Sodroski J. Relationship of the human immunodeficiency virus type 1 gp120 third variable loop to a component of the CD4 binding site in the fourth conserved region. J Virol. 1992 Dec;66(12):6997–7004. doi: 10.1128/jvi.66.12.6997-7004.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  50. Yoshiyama H., Nakashima H., Kobayashi S., Yamamoto N. Differential neutralizing capacity to different human immunodeficiency virus (HIV) isolates by a rabbit antiserum against LAV: sensitive assays with HTLV-I-positive MT-4 cells. AIDS Res Hum Retroviruses. 1988 Apr;4(2):91–98. doi: 10.1089/aid.1988.4.91. [DOI] [PubMed] [Google Scholar]
  51. Zolla-Pazner S., Gorny M. K. Passive immunization for the prevention and treatment of HIV infection. AIDS. 1992 Nov;6(11):1235–1247. doi: 10.1097/00002030-199211000-00001. [DOI] [PubMed] [Google Scholar]

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