Skip to main content
NCBI home page
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1990 Apr;87(8):3185–3189. doi: 10.1073/pnas.87.8.3185

Human monoclonal antibodies to the human immunodeficiency virus type 1 (HIV-1) transmembrane glycoprotein gp41 enhance HIV-1 infection in vitro.

W E Robinson Jr 1, T Kawamura 1, M K Gorny 1, D Lake 1, J Y Xu 1, Y Matsumoto 1, T Sugano 1, Y Masuho 1, W M Mitchell 1, E Hersh 1, et al.
PMCID: PMC53860  PMID: 2326277

Abstract

Three of 16 human monoclonal antibodies (hu-mAbs) enhanced human immunodeficiency virus type 1 (HIV-1) infection of MT-2 target cells by means of a mechanism that is dependent on complement. Enhanced infections are characterized by an increase in cytopathic effects and antigen synthesis as well as an increase in the production of progeny virus as detected by release of reverse transcriptase activity and infectious virus into the culture medium. Analyses by radioimmunoprecipitation, Western blot, and ELISA using the pENV9 envelope fragment localize the antigenic specificities of these three hu-mAbs to the N-terminal two-thirds of the transmembrane protein gp41. Competitive binding experiments indicate that the hu-mAbs are reactive with immunodominant epitopes of gp41 recognized by sera from essentially all HIV-1-infected subjects. Combination dose-effect experiments demonstrate that these hu-mAbs can act synergistically in vitro to enhance HIV-1 infection. These data demonstrate that hu-mAbs directed against the HIV-1 transmembrane glycoprotein gp41 can enhance HIV-1 infection in vitro. The availability of these reagents allows for the mapping of enhancing epitopes on HIV-1 and provides a means for studying whether deletion of such enhancing epitopes from candidate HIV-1 vaccines might improve the protective immune response to HIV-1 in immunized humans and chimpanzees.

Full text

PDF
3185

Images in this article

3188Image
on p.3188

Selected References

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

  1. Antibody-dependent enhancement of HIV infection. Lancet. 1988 Jun 4;1(8597):1285–1286. [PubMed] [Google Scholar]
  2. Antibody-dependent enhancement of HIV infection. Lancet. 1988 Jun 4;1(8597):1285–1286. [PubMed] [Google Scholar]
  3. Barrett A. D., Gould E. A. Antibody-mediated early death in vivo after infection with yellow fever virus. J Gen Virol. 1986 Nov;67(Pt 11):2539–2542. doi: 10.1099/0022-1317-67-11-2539. [DOI] [PubMed] [Google Scholar]
  4. 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]
  5. Berman P. W., Groopman J. E., Gregory T., Clapham P. R., Weiss R. A., Ferriani R., Riddle L., Shimasaki C., Lucas C., Lasky L. A. Human immunodeficiency virus type 1 challenge of chimpanzees immunized with recombinant envelope glycoprotein gp120. Proc Natl Acad Sci U S A. 1988 Jul;85(14):5200–5204. doi: 10.1073/pnas.85.14.5200. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Cardosa M. J., Porterfield J. S., Gordon S. Complement receptor mediates enhanced flavivirus replication in macrophages. J Exp Med. 1983 Jul 1;158(1):258–263. doi: 10.1084/jem.158.1.258. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. 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]
  8. 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]
  9. Gallo R. C., Sarin P. S., Gelmann E. P., Robert-Guroff M., Richardson E., Kalyanaraman V. S., Mann D., Sidhu G. D., Stahl R. E., Zolla-Pazner S. Isolation of human T-cell leukemia virus in acquired immune deficiency syndrome (AIDS). Science. 1983 May 20;220(4599):865–867. doi: 10.1126/science.6601823. [DOI] [PubMed] [Google Scholar]
  10. 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]
  11. Halstead S. B. In vivo enhancement of dengue virus infection in rhesus monkeys by passively transferred antibody. J Infect Dis. 1979 Oct;140(4):527–533. doi: 10.1093/infdis/140.4.527. [DOI] [PubMed] [Google Scholar]
  12. Homsy J., Meyer M., Tateno M., Clarkson S., Levy J. A. The Fc and not CD4 receptor mediates antibody enhancement of HIV infection in human cells. Science. 1989 Jun 16;244(4910):1357–1360. doi: 10.1126/science.2786647. [DOI] [PubMed] [Google Scholar]
  13. Hu S. L., Fultz P. N., McClure H. M., Eichberg J. W., Thomas E. K., Zarling J., Singhal M. C., Kosowski S. G., Swenson R. B., Anderson D. C. Effect of immunization with a vaccinia-HIV env recombinant on HIV infection of chimpanzees. Nature. 1987 Aug 20;328(6132):721–723. doi: 10.1038/328721a0. [DOI] [PubMed] [Google Scholar]
  14. Jouault T., Chapuis F., Olivier R., Parravicini C., Bahraoui E., Gluckman J. C. HIV infection of monocytic cells: rôle of antibody-mediated virus binding to Fc-gamma receptors. AIDS. 1989 Mar;3(3):125–133. [PubMed] [Google Scholar]
  15. Kliks S. C., Nisalak A., Brandt W. E., Wahl L., Burke D. S. Antibody-dependent enhancement of dengue virus growth in human monocytes as a risk factor for dengue hemorrhagic fever. Am J Trop Med Hyg. 1989 Apr;40(4):444–451. doi: 10.4269/ajtmh.1989.40.444. [DOI] [PubMed] [Google Scholar]
  16. Liu Y. S., Green A. A monoclonal-antibody enzyme immunoassay for detection of hepatitis B surface antigen with use of a biotin-avidin system. Clin Chem. 1985 Feb;31(2):202–205. [PubMed] [Google Scholar]
  17. Montefiori D. C., Mitchell W. M. Persistent coinfection of T lymphocytes with HTLV-II and HIV and the role of syncytium formation in HIV-induced cytopathic effect. Virology. 1987 Oct;160(2):372–378. doi: 10.1016/0042-6822(87)90008-0. [DOI] [PubMed] [Google Scholar]
  18. 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]
  19. Montefiori D. C., Robinson W. E., Jr, Mitchell W. M. In vitro evaluation of mismatched double-stranded RNA (ampligen) for combination therapy in the treatment of acquired immunodeficiency syndrome. AIDS Res Hum Retroviruses. 1989 Apr;5(2):193–203. doi: 10.1089/aid.1989.5.193. [DOI] [PubMed] [Google Scholar]
  20. 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]
  21. 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]
  22. 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]
  23. Poiesz B. J., Ruscetti F. W., Gazdar A. F., Bunn P. A., Minna J. D., Gallo R. C. Detection and isolation of type C retrovirus particles from fresh and cultured lymphocytes of a patient with cutaneous T-cell lymphoma. Proc Natl Acad Sci U S A. 1980 Dec;77(12):7415–7419. doi: 10.1073/pnas.77.12.7415. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Prince A. M., Horowitz B., Baker L., Shulman R. W., Ralph H., Valinsky J., Cundell A., Brotman B., Boehle W., Rey F. Failure of a human immunodeficiency virus (HIV) immune globulin to protect chimpanzees against experimental challenge with HIV. Proc Natl Acad Sci U S A. 1988 Sep;85(18):6944–6948. doi: 10.1073/pnas.85.18.6944. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Putney S. D., Matthews T. J., Robey W. G., Lynn D. L., Robert-Guroff M., Mueller W. T., Langlois A. J., Ghrayeb J., Petteway S. R., Jr, Weinhold K. J. HTLV-III/LAV-neutralizing antibodies to an E. coli-produced fragment of the virus envelope. Science. 1986 Dec 12;234(4782):1392–1395. doi: 10.1126/science.2431482. [DOI] [PubMed] [Google Scholar]
  26. 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]
  27. Robinson W. E., Jr, Montefiori D. C., Mitchell W. M. A human immunodeficiency virus type 1 (HIV-1) infection-enhancing factor in seropositive sera. Biochem Biophys Res Commun. 1987 Dec 16;149(2):693–699. doi: 10.1016/0006-291x(87)90423-2. [DOI] [PubMed] [Google Scholar]
  28. 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]
  29. Robinson W. E., Jr, Montefiori D. C., Mitchell W. M., Prince A. M., Alter H. J., Dreesman G. R., Eichberg J. W. Antibody-dependent enhancement of human immunodeficiency virus type 1 (HIV-1) infection in vitro by serum from HIV-1-infected and passively immunized chimpanzees. Proc Natl Acad Sci U S A. 1989 Jun;86(12):4710–4714. doi: 10.1073/pnas.86.12.4710. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. 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]
  31. 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]
  32. Takeda A., Tuazon C. U., Ennis F. A. Antibody-enhanced infection by HIV-1 via Fc receptor-mediated entry. Science. 1988 Oct 28;242(4878):580–583. doi: 10.1126/science.2972065. [DOI] [PubMed] [Google Scholar]
  33. Weiss R. A., Clapham P. R., Cheingsong-Popov R., Dalgleish A. G., Carne C. A., Weller I. V., Tedder R. S. Neutralization of human T-lymphotropic virus type III by sera of AIDS and AIDS-risk patients. Nature. 1985 Jul 4;316(6023):69–72. doi: 10.1038/316069a0. [DOI] [PubMed] [Google Scholar]
  34. Weiss R. A., Clapham P. R., Weber J. N., Dalgleish A. G., Lasky L. A., Berman P. W. Variable and conserved neutralization antigens of human immunodeficiency virus. Nature. 1986 Dec 11;324(6097):572–575. doi: 10.1038/324572a0. [DOI] [PubMed] [Google Scholar]
  35. 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 Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES