Antibody cross-competition analysis of the human immunodeficiency virus type 1 gp120 exterior envelope glycoprotein (original) (raw)

Abstract

Forty-six monoclonal antibodies (MAbs) able to bind to the native, monomeric gp120 glycoprotein of the human immunodeficiency virus type 1 (HIV-1) LAI (HXBc2) strain were used to generate a competition matrix. The data suggest the existence of two faces of the gp120 glycoprotein. The binding sites for the viral receptor, CD4, and neutralizing MAbs appear to cluster on one face, which is presumably exposed on the assembled, oligomeric envelope glycoprotein complex. A second gp120 face, which is presumably inaccessible on the envelope glycoprotein complex, contains a number of epitopes for nonneutralizing antibodies. This analysis should be useful for understanding both the interaction of antibodies with the HIV-1 gp120 glycoprotein and neutralization of HIV-1.

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Selected References

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  1. Allaway G. P., Ryder A. M., Beaudry G. A., Maddon P. J. Synergistic inhibition of HIV-1 envelope-mediated cell fusion by CD4-based molecules in combination with antibodies to gp120 or gp41. AIDS Res Hum Retroviruses. 1993 Jul;9(7):581–587. doi: 10.1089/aid.1993.9.581. [DOI] [PubMed] [Google Scholar]
  2. 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]
  3. Buchacher A., Predl R., Strutzenberger K., Steinfellner W., Trkola A., Purtscher M., Gruber G., Tauer C., Steindl F., Jungbauer A. Generation of human monoclonal antibodies against HIV-1 proteins; electrofusion and Epstein-Barr virus transformation for peripheral blood lymphocyte immortalization. AIDS Res Hum Retroviruses. 1994 Apr;10(4):359–369. doi: 10.1089/aid.1994.10.359. [DOI] [PubMed] [Google Scholar]
  4. Buchbinder A., Karwowska S., Gorny M. K., Burda S. T., Zolla-Pazner S. Synergy between human monoclonal antibodies to HIV extends their effective biologic activity against homologous and divergent strains. AIDS Res Hum Retroviruses. 1992 Apr;8(4):425–427. doi: 10.1089/aid.1992.8.425. [DOI] [PubMed] [Google Scholar]
  5. Burton D. R., Pyati J., Koduri R., Sharp S. J., Thornton G. B., Parren P. W., Sawyer L. S., Hendry R. M., Dunlop N., Nara P. L. Efficient neutralization of primary isolates of HIV-1 by a recombinant human monoclonal antibody. Science. 1994 Nov 11;266(5187):1024–1027. doi: 10.1126/science.7973652. [DOI] [PubMed] [Google Scholar]
  6. Capon D. J., Chamow S. M., Mordenti J., Marsters S. A., Gregory T., Mitsuya H., Byrn R. A., Lucas C., Wurm F. M., Groopman J. E. Designing CD4 immunoadhesins for AIDS therapy. Nature. 1989 Feb 9;337(6207):525–531. doi: 10.1038/337525a0. [DOI] [PubMed] [Google Scholar]
  7. Choe H. R., Sodroski J. Adaptation of human immunodeficiency virus type 1 to cells expressing a binding-deficient CD4 mutant (lysine 46 to aspartic acid). J Virol. 1995 May;69(5):2801–2810. doi: 10.1128/jvi.69.5.2801-2810.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Decroly E., Cornet B., Martin I., Ruysschaert J. M., Vandenbranden M. Secondary structure of gp160 and gp120 envelope glycoproteins of human immunodeficiency virus type 1: a Fourier transform infrared spectroscopic study. J Virol. 1993 Jun;67(6):3552–3560. doi: 10.1128/jvi.67.6.3552-3560.1993. [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. Gallaher W. R., Ball J. M., Garry R. F., Martin-Amedee A. M., Montelaro R. C. A general model for the surface glycoproteins of HIV and other retroviruses. AIDS Res Hum Retroviruses. 1995 Feb;11(2):191–202. doi: 10.1089/aid.1995.11.191. [DOI] [PubMed] [Google Scholar]
  12. 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]
  13. 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]
  14. 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]
  15. 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]
  16. Kang C. Y., Hariharan K., Nara P. L., Sodroski J., Moore J. P. Immunization with a soluble CD4-gp120 complex preferentially induces neutralizing anti-human immunodeficiency virus type 1 antibodies directed to conformation-dependent epitopes of gp120. J Virol. 1994 Sep;68(9):5854–5862. doi: 10.1128/jvi.68.9.5854-5862.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Koito A., Stamatatos L., Cheng-Mayer C. Small amino acid sequence changes within the V2 domain can affect the function of a T-cell line-tropic human immunodeficiency virus type 1 envelope gp120. Virology. 1995 Feb 1;206(2):878–884. doi: 10.1006/viro.1995.1010. [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. Langedijk J. P., Back N. K., Kinney-Thomas E., Bruck C., Francotte M., Goudsmit J., Meloen R. H. Comparison and fine mapping of both high and low neutralizing monoclonal antibodies against the principal neutralization domain of HIV-1. Arch Virol. 1992;126(1-4):129–146. doi: 10.1007/BF01309690. [DOI] [PubMed] [Google Scholar]
  20. 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]
  21. McKeating J. A., Cordell J., Dean C. J., Balfe P. Synergistic interaction between ligands binding to the CD4 binding site and V3 domain of human immunodeficiency virus type I gp120. Virology. 1992 Dec;191(2):732–742. doi: 10.1016/0042-6822(92)90249-o. [DOI] [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., Sattentau Q. J., Wyatt R., Sodroski J. Probing the structure of the human immunodeficiency virus surface glycoprotein gp120 with a panel of monoclonal antibodies. J Virol. 1994 Jan;68(1):469–484. doi: 10.1128/jvi.68.1.469-484.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. 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]
  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., Willey R. L., Lewis G. K., Robinson J., Sodroski J. Immunological evidence for interactions between the first, second, and fifth conserved domains of the gp120 surface glycoprotein of human immunodeficiency virus type 1. J Virol. 1994 Nov;68(11):6836–6847. doi: 10.1128/jvi.68.11.6836-6847.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Niedrig M., Harthus H. P., Hinkula J., Bröker M., Bickhard H., Pauli G., Gelderblom H. R., Wahren B. Inhibition of viral replication by monoclonal antibodies directed against human immunodeficiency virus gp120. J Gen Virol. 1992 Sep;73(Pt 9):2451–2455. doi: 10.1099/0022-1317-73-9-2451. [DOI] [PubMed] [Google Scholar]
  32. 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]
  33. Potts B. J., Field K. G., Wu Y., Posner M., Cavacini L., White-Scharf M. Synergistic inhibition of HIV-1 by CD4 binding domain reagents and V3-directed monoclonal antibodies. Virology. 1993 Nov;197(1):415–419. doi: 10.1006/viro.1993.1604. [DOI] [PubMed] [Google Scholar]
  34. Roben P., Moore J. P., Thali M., Sodroski J., Barbas C. F., 3rd, Burton D. R. Recognition properties of a panel of human recombinant Fab fragments to the CD4 binding site of gp120 that show differing abilities to neutralize human immunodeficiency virus type 1. J Virol. 1994 Aug;68(8):4821–4828. doi: 10.1128/jvi.68.8.4821-4828.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. 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]
  36. Sattentau Q. J., Moore J. P., Vignaux F., Traincard F., Poignard P. Conformational changes induced in the envelope glycoproteins of the human and simian immunodeficiency viruses by soluble receptor binding. J Virol. 1993 Dec;67(12):7383–7393. doi: 10.1128/jvi.67.12.7383-7393.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Schutten M., Andeweg A. C., Bosch M. L., Osterhaus A. D. Enhancement of infectivity of a non-syncytium inducing HIV-1 by sCD4 and by human antibodies that neutralize syncytium inducing HIV-1. Scand J Immunol. 1995 Jan;41(1):18–22. doi: 10.1111/j.1365-3083.1995.tb03528.x. [DOI] [PubMed] [Google Scholar]
  38. Shotton C., Arnold C., Sattentau Q., Sodroski J., McKeating J. A. Identification and characterization of monoclonal antibodies specific for polymorphic antigenic determinants within the V2 region of the human immunodeficiency virus type 1 envelope glycoprotein. J Virol. 1995 Jan;69(1):222–230. doi: 10.1128/jvi.69.1.222-230.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Skinner M. A., Ting R., Langlois A. J., Weinhold K. J., Lyerly H. K., Javaherian K., Matthews T. J. Characteristics of a neutralizing monoclonal antibody to the HIV envelope glycoprotein. AIDS Res Hum Retroviruses. 1988 Jun;4(3):187–197. doi: 10.1089/aid.1988.4.187. [DOI] [PubMed] [Google Scholar]
  40. Stamatatos L., Cheng-Mayer C. Evidence that the structural conformation of envelope gp120 affects human immunodeficiency virus type 1 infectivity, host range, and syncytium-forming ability. J Virol. 1993 Sep;67(9):5635–5639. doi: 10.1128/jvi.67.9.5635-5639.1993. [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. 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]
  43. Sullivan N., Sun Y., Li J., Hofmann W., Sodroski J. Replicative function and neutralization sensitivity of envelope glycoproteins from primary and T-cell line-passaged human immunodeficiency virus type 1 isolates. J Virol. 1995 Jul;69(7):4413–4422. doi: 10.1128/jvi.69.7.4413-4422.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. 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]
  45. 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]
  46. 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]
  47. Thali M., Furman C., Wahren B., Posner M., Ho D. D., Robinson J., Sodroski J. Cooperativity of neutralizing antibodies directed against the V3 and CD4 binding regions of the human immunodeficiency virus gp120 envelope glycoprotein. J Acquir Immune Defic Syndr. 1992;5(6):591–599. [PubMed] [Google Scholar]
  48. 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]
  49. 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]
  50. 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]
  51. 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]
  52. Trkola A., Purtscher M., Muster T., Ballaun C., Buchacher A., Sullivan N., Srinivasan K., Sodroski J., Moore J. P., Katinger H. Human monoclonal antibody 2G12 defines a distinctive neutralization epitope on the gp120 glycoprotein of human immunodeficiency virus type 1. J Virol. 1996 Feb;70(2):1100–1108. doi: 10.1128/jvi.70.2.1100-1108.1996. [DOI] [PMC free article] [PubMed] [Google Scholar]
  53. Willey R. L., Ross E. K., Buckler-White A. J., Theodore T. S., Martin M. A. Functional interaction of constant and variable domains of human immunodeficiency virus type 1 gp120. J Virol. 1989 Sep;63(9):3595–3600. doi: 10.1128/jvi.63.9.3595-3600.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  54. Willey R. L., Smith D. H., Lasky L. A., Theodore T. S., Earl P. L., Moss B., Capon D. J., Martin M. A. In vitro mutagenesis identifies a region within the envelope gene of the human immunodeficiency virus that is critical for infectivity. J Virol. 1988 Jan;62(1):139–147. doi: 10.1128/jvi.62.1.139-147.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  55. Wyatt R., Moore J., Accola M., Desjardin E., Robinson J., Sodroski J. Involvement of the V1/V2 variable loop structure in the exposure of human immunodeficiency virus type 1 gp120 epitopes induced by receptor binding. J Virol. 1995 Sep;69(9):5723–5733. doi: 10.1128/jvi.69.9.5723-5733.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  56. 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]
  57. 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]
  58. di Marzo Veronese F., Rahman R., Pal R., Boyer C., Romano J., Kalyanaraman V. S., Nair B. C., Gallo R. C., Sarngadharan M. G. Delineation of immunoreactive, conserved regions in the external glycoprotein of the human immunodeficiency virus type 1. AIDS Res Hum Retroviruses. 1992 Jun;8(6):1125–1132. doi: 10.1089/aid.1992.8.1125. [DOI] [PubMed] [Google Scholar]