Skip to main content
NCBI home page
Journal of Virology logoLink to Journal of Virology
. 1991 Aug;65(8):4169–4176. doi: 10.1128/jvi.65.8.4169-4176.1991

Two immunodominant domains of gp41 bind antibodies which enhance human immunodeficiency virus type 1 infection in vitro.

W E Robinson Jr 1, M K Gorny 1, J Y Xu 1, W M Mitchell 1, S Zolla-Pazner 1
PMCID: PMC248851  PMID: 2072448

Abstract

Four of eight human monoclonal antibodies (huMAbs) to gp41 were identified which could enhance human immunodeficiency virus type 1 (HIV-1) infection in vitro by complement-mediated antibody-dependent enhancement (C'-ADE). These enhancing huMAbs were mapped to two distinct domains on the HIV-1 gp41 transmembrane glycoprotein by using synthetic peptides. The first domain, amino acids 579 to 613 (peptide AA579-613), was recognized by three of the four enhancing huMAbs. The AA579-613 peptide blocked C'-ADE of HIV-1 infection in vitro whether it was mediated by these three huMAbs or by human polyclonal anti-HIV serum. The second domain, amino acids 644 to 663, bound the remaining enhancing huMAb. This peptide weakly blocked C'-ADE mediated by the huMAb and by an HIV immune globulin fraction but did not block C'-ADE mediated by a patient's serum. The patient's serum did react with the peptide in an enzyme immunoassay. The huMAbs to the two domains could interact in vitro to enhance HIV-1 infection in a synergistic manner. These two domains, which bind enhancing antibodies, are conserved between HIV-1 isolates as well as between HIV-2 and simian immunodeficiency virus isolates. These data demonstrate the existence of two conserved regions within the HIV-1 gp41 which bind enhancing antibodies; these two domains, amino acids 579 to 613 and 644 to 663, may prove important in HIV-1 vaccine development and in immunopathogenesis of HIV-1 infection.

Full text

PDF
4169

Selected References

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

  1. Banapour B., Rosenthal K., Rabin L., Sharma V., Young L., Fernandez J., Engleman E., McGrath M., Reyes G., Lifson J. Characterization and epitope mapping of a human monoclonal antibody reactive with the envelope glycoprotein of human immunodeficiency virus. J Immunol. 1987 Dec 15;139(12):4027–4033. [PubMed] [Google Scholar]
  2. Berman P. W., Gregory T. J., Riddle L., Nakamura G. R., Champe M. A., Porter J. P., Wurm F. M., Hershberg R. D., Cobb E. K., Eichberg J. W. Protection of chimpanzees from infection by HIV-1 after vaccination with recombinant glycoprotein gp120 but not gp160. Nature. 1990 Jun 14;345(6276):622–625. doi: 10.1038/345622a0. [DOI] [PubMed] [Google Scholar]
  3. Broliden P. A., Ljunggren K., Hinkula J., Norrby E., Akerblom L., Wahren B. A monoclonal antibody to human immunodeficiency virus type 1 which mediates cellular cytotoxicity and neutralization. J Virol. 1990 Feb;64(2):936–940. doi: 10.1128/jvi.64.2.936-940.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Chanh T. C., Dreesman G. R., Kanda P., Linette G. P., Sparrow J. T., Ho D. D., Kennedy R. C. Induction of anti-HIV neutralizing antibodies by synthetic peptides. EMBO J. 1986 Nov;5(11):3065–3071. doi: 10.1002/j.1460-2075.1986.tb04607.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Chiodi F., von Gegerfeldt A., Albert J., Fenyö E. M., Gaines H., von Sydow M., Biberfeld G., Parks E., Norrby E. Site-directed ELISA with synthetic peptides representing the HIV transmembrane glycoprotein. J Med Virol. 1987 Sep;23(1):1–9. doi: 10.1002/jmv.1890230102. [DOI] [PubMed] [Google Scholar]
  6. Chou T. C., Talalay P. Quantitative analysis of dose-effect relationships: the combined effects of multiple drugs or enzyme inhibitors. Adv Enzyme Regul. 1984;22:27–55. doi: 10.1016/0065-2571(84)90007-4. [DOI] [PubMed] [Google Scholar]
  7. Dalgleish A. G., Chanh T. C., Kennedy R. C., Kanda P., Clapham P. R., Weiss R. A. Neutralization of diverse HIV-1 strains by monoclonal antibodies raised against a gp41 synthetic peptide. Virology. 1988 Jul;165(1):209–215. doi: 10.1016/0042-6822(88)90674-5. [DOI] [PubMed] [Google Scholar]
  8. Desgranges C., Boyer V., Souche S., Sprecher S., Burney A., Gallo R. C., Bernard J., Reveil B., Zagury D. Monoclonal antibodies to HIV in a non-infected, immunised volunteer. Lancet. 1988 Apr 23;1(8591):935–936. doi: 10.1016/s0140-6736(88)91737-0. [DOI] [PubMed] [Google Scholar]
  9. Desrosiers R. C., Wyand M. S., Kodama T., Ringler D. J., Arthur L. O., Sehgal P. K., Letvin N. L., King N. W., Daniel M. D. Vaccine protection against simian immunodeficiency virus infection. Proc Natl Acad Sci U S A. 1989 Aug;86(16):6353–6357. doi: 10.1073/pnas.86.16.6353. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Durda P. J., Leece B., Jenoski A., Rabin H., Fisher A., Wong-Staal F. Characterization of murine monoclonal antibodies to HIV-1 induced by synthetic peptides. AIDS Res Hum Retroviruses. 1988 Oct;4(5):331–342. doi: 10.1089/aid.1988.4.331. [DOI] [PubMed] [Google Scholar]
  11. Evans L. A., Homsy J. M., Morrow W. J., Gaston I., Sooy C. D., Levy J. A. Human monoclonal antibody directed against gag gene products of the human immunodeficiency virus. J Immunol. 1988 Feb 1;140(3):941–943. [PubMed] [Google Scholar]
  12. Ferns R. B., Partridge J. C., Spence R. P., Hunt N., Tedder R. S. Epitope location of 13 anti-gag HIV-1 monoclonal antibodies using oligopeptides and their cross reactivity with HIV-2. AIDS. 1989 Dec;3(12):829–834. doi: 10.1097/00002030-198912000-00008. [DOI] [PubMed] [Google Scholar]
  13. 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]
  14. Gorny M. K., Gianakakos V., Sharpe S., Zolla-Pazner S. Generation of human monoclonal antibodies to human immunodeficiency virus. Proc Natl Acad Sci U S A. 1989 Mar;86(5):1624–1628. doi: 10.1073/pnas.86.5.1624. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Gorny M. K., Xu J. Y., Gianakakos V., Karwowska S., Williams C., Sheppard H. W., Hanson C. V., Zolla-Pazner S. Production of site-selected neutralizing human monoclonal antibodies against the third variable domain of the human immunodeficiency virus type 1 envelope glycoprotein. Proc Natl Acad Sci U S A. 1991 Apr 15;88(8):3238–3242. doi: 10.1073/pnas.88.8.3238. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Grunow R., Jahn S., Porstmann T., Kiessig S. S., Steinkellner H., Steindl F., Mattanovich D., Gürtler L., Deinhardt F., Katinger H. The high efficiency, human B cell immortalizing heteromyeloma CB-F7. Production of human monoclonal antibodies to human immunodeficiency virus. J Immunol Methods. 1988 Feb 10;106(2):257–265. doi: 10.1016/0022-1759(88)90206-2. [DOI] [PubMed] [Google Scholar]
  17. Homsy J., Meyer M., Levy J. A. Serum enhancement of human immunodeficiency virus (HIV) infection correlates with disease in HIV-infected individuals. J Virol. 1990 Apr;64(4):1437–1440. doi: 10.1128/jvi.64.4.1437-1440.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Klasse P. J., Pipkorn R., Blomberg J. Presence of antibodies to a putatively immunosuppressive part of human immunodeficiency virus (HIV) envelope glycoprotein gp41 is strongly associated with health among HIV-positive subjects. Proc Natl Acad Sci U S A. 1988 Jul;85(14):5225–5229. doi: 10.1073/pnas.85.14.5225. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Kodama T., Ohta Y., Masuda T., Ishikawa K., Tsujimoto H., Isahakia M., Hayami M. Production and characterization of monoclonal antibodies specific for the transmembrane protein of simian immunodeficiency virus from the African green monkey. J Virol. 1988 Dec;62(12):4782–4785. doi: 10.1128/jvi.62.12.4782-4785.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Matsushita S., Robert-Guroff M., Rusche J., Koito A., Hattori T., Hoshino H., Javaherian K., Takatsuki K., Putney S. Characterization of a human immunodeficiency virus neutralizing monoclonal antibody and mapping of the neutralizing epitope. J Virol. 1988 Jun;62(6):2107–2114. doi: 10.1128/jvi.62.6.2107-2114.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Montefiori D. C., Robinson W. E., Jr, Hirsch V. M., Modliszewski A., Mitchell W. M., Johnson P. R. Antibody-dependent enhancement of simian immunodeficiency virus (SIV) infection in vitro by plasma from SIV-infected rhesus macaques. J Virol. 1990 Jan;64(1):113–119. doi: 10.1128/jvi.64.1.113-119.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Montefiori D. C., Robinson W. E., Jr, Schuffman S. S., Mitchell W. M. Evaluation of antiviral drugs and neutralizing antibodies to human immunodeficiency virus by a rapid and sensitive microtiter infection assay. J Clin Microbiol. 1988 Feb;26(2):231–235. doi: 10.1128/jcm.26.2.231-235.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Murphey-Corb M., Martin L. N., Davison-Fairburn B., Montelaro R. C., Miller M., West M., Ohkawa S., Baskin G. B., Zhang J. Y., Putney S. D. A formalin-inactivated whole SIV vaccine confers protection in macaques. Science. 1989 Dec 8;246(4935):1293–1297. doi: 10.1126/science.2555923. [DOI] [PubMed] [Google Scholar]
  24. Papsidero L. D., Sheu M., Ruscetti F. W. Human immunodeficiency virus type 1-neutralizing monoclonal antibodies which react with p17 core protein: characterization and epitope mapping. J Virol. 1989 Jan;63(1):267–272. doi: 10.1128/jvi.63.1.267-272.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Pinter A., Honnen W. J., Tilley S. A., Bona C., Zaghouani H., Gorny M. K., Zolla-Pazner S. Oligomeric structure of gp41, the transmembrane protein of human immunodeficiency virus type 1. J Virol. 1989 Jun;63(6):2674–2679. doi: 10.1128/jvi.63.6.2674-2679.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Robinson W. E., Jr, Kawamura T., Gorny M. K., Lake D., Xu J. Y., Matsumoto Y., Sugano T., Masuho Y., Mitchell W. M., Hersh E. Human monoclonal antibodies to the human immunodeficiency virus type 1 (HIV-1) transmembrane glycoprotein gp41 enhance HIV-1 infection in vitro. Proc Natl Acad Sci U S A. 1990 Apr;87(8):3185–3189. doi: 10.1073/pnas.87.8.3185. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. 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]
  28. Robinson W. E., Jr, Montefiori D. C., Gillespie D. H., Mitchell W. M. Complement-mediated, antibody-dependent enhancement of HIV-1 infection in vitro is characterized by increased protein and RNA syntheses and infectious virus release. J Acquir Immune Defic Syndr. 1989;2(1):33–42. [PubMed] [Google Scholar]
  29. Robinson W. E., Jr, Montefiori D. C., Mitchell W. M. Antibody-dependent enhancement of human immunodeficiency virus type 1 infection. Lancet. 1988 Apr 9;1(8589):790–794. doi: 10.1016/s0140-6736(88)91657-1. [DOI] [PubMed] [Google Scholar]
  30. Robinson W. E., Jr, Montefiori D. C., Mitchell W. M. Complement-mediated antibody-dependent enhancement of HIV-1 infection requires CD4 and complement receptors. Virology. 1990 Apr;175(2):600–604. doi: 10.1016/0042-6822(90)90449-2. [DOI] [PubMed] [Google Scholar]
  31. Robinson W. E., Jr, Montefiori D. C., Mitchell W. M. Will antibody-dependent enhancement of HIV-1 infection be a problem with AIDS vaccines? Lancet. 1988 Apr 9;1(8589):830–831. doi: 10.1016/s0140-6736(88)91695-9. [DOI] [PubMed] [Google Scholar]
  32. Schrier R. D., Gnann J. W., Jr, Langlois A. J., Shriver K., Nelson J. A., Oldstone M. B. B- and T-lymphocyte responses to an immunodominant epitope of human immunodeficiency virus. J Virol. 1988 Aug;62(8):2531–2536. doi: 10.1128/jvi.62.8.2531-2536.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. 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]
  34. Smith R. S., Naso R. B., Rosen J., Whalley A., Hom Y. L., Hoey K., Kennedy C. J., McCutchan J. A., Spector S. A., Richman D. D. Antibody to a synthetic oligopeptide in subjects at risk for human immunodeficiency virus infection. J Clin Microbiol. 1987 Aug;25(8):1498–1504. doi: 10.1128/jcm.25.8.1498-1504.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Sugano T., Masuho Y., Matsumoto Y., Lake D., Gschwind C., Petersen E. A., Hersh E. M. Human monoclonal antibody against glycoproteins of human immunodeficiency virus. Biochem Biophys Res Commun. 1988 Sep 30;155(3):1105–1112. doi: 10.1016/s0006-291x(88)81254-3. [DOI] [PubMed] [Google Scholar]
  36. Sutjipto S., Pedersen N. C., Miller C. J., Gardner M. B., Hanson C. V., Gettie A., Jennings M., Higgins J., Marx P. A. Inactivated simian immunodeficiency virus vaccine failed to protect rhesus macaques from intravenous or genital mucosal infection but delayed disease in intravenously exposed animals. J Virol. 1990 May;64(5):2290–2297. doi: 10.1128/jvi.64.5.2290-2297.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Teng N. N., Lam K. S., Calvo Riera F., Kaplan H. S. Construction and testing of mouse--human heteromyelomas for human monoclonal antibody production. Proc Natl Acad Sci U S A. 1983 Dec;80(23):7308–7312. doi: 10.1073/pnas.80.23.7308. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. 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]
  39. Tyler D. S., Stanley S. D., Zolla-Pazner S., Gorny M. K., Shadduck P. P., Langlois A. J., Matthews T. J., Bolognesi D. P., Palker T. J., Weinhold K. J. Identification of sites within gp41 that serve as targets for antibody-dependent cellular cytotoxicity by using human monoclonal antibodies. J Immunol. 1990 Nov 15;145(10):3276–3282. [PubMed] [Google Scholar]
  40. Zolla-Pazner S., Gorny M. K., Honnen W. J., Pinter A. Reinterpretation of human immunodeficiency virus western blot patterns. N Engl J Med. 1989 May 11;320(19):1280–1281. doi: 10.1056/NEJM198905113201914. [DOI] [PubMed] [Google Scholar]

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

RESOURCES