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. 1996 Aug;70(8):5213–5220. doi: 10.1128/jvi.70.8.5213-5220.1996

Inhibition of human immunodeficiency virus type 1 production in infected peripheral blood mononuclear cells by human leukocyte antigen class I-specific antibodies: evidence for a novel antiviral mechanism.

L Briant 1, M Benkirane 1, M Girard 1, M Hirn 1, C Iosef 1, C Devaux 1
PMCID: PMC190477  PMID: 8764030

Abstract

A well-characterized mechanism by which anti-HLA class I monoclonal antibodies (MAb) inhibit human immunodeficiency virus type 1 (HIV-1) propagation in in vitro cell cultures is the neutralization of the virus through interactions with HLA molecules associated with the virion envelope. Yet, the possibility that another mechanism of inhibition might affect a postbinding stage of the virus life cycle has been strongly suggested by our previous investigations. To demonstrate that the interaction of MAb B1-1G6 with the light chain of cell surface-expressed HLA class I molecules inhibits a postbinding step of the HIV-1 life cycle, peripheral blood mononuclear cells (PBMCs) were exposed to viruses grown in HLA class I-negative, CD4-positive cells (these viruses, which did not carry HLA class I molecules, cannot be neutralized by anti-HLA MAb during the first round of infection), and PCR was used at various times postexposure to search for the different forms of HIV-1 DNA and RNA in virus-exposed PBMCs cultured in either the presence or [correction of] absence of MAb B1-1G6. Although viral DNA was found in MAb B1-1G6-treated cells, spliced HIV-1 mRNA could not be detected in those cells. In contrast, HIV-1 gene expression was found in HIV-1-infected PBMCs treated with B9-12-1, another HLA class I-specific MAb which prevents infection of cells by cell-free viruses but which fails to inhibit cell-to-cell transmission of HIV-1. These results highlight a second antiviral mechanism by which anti-HLA MAb inhibit in vitro HIV-1 propagation.

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Selected References

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  1. Arthur L. O., Bess J. W., Jr, Sowder R. C., 2nd, Benveniste R. E., Mann D. L., Chermann J. C., Henderson L. E. Cellular proteins bound to immunodeficiency viruses: implications for pathogenesis and vaccines. Science. 1992 Dec 18;258(5090):1935–1938. doi: 10.1126/science.1470916. [DOI] [PubMed] [Google Scholar]
  2. Beckman I., Xiaoning X., Bradley J. Specific inhibition of OKT3-driven T-cell mitogenesis by an anti HLA-class I monoclonal antibody. Immunology. 1988 Nov;65(3):373–378. [PMC free article] [PubMed] [Google Scholar]
  3. Benkirane M., Blanc-Zouaoui D., Hirn M., Devaux C. Involvement of human leukocyte antigen class I molecules in human immunodeficiency virus infection of CD4-positive cells. J Virol. 1994 Oct;68(10):6332–6339. doi: 10.1128/jvi.68.10.6332-6339.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Benkirane M., Corbeau P., Housset V., Devaux C. An antibody that binds the immunoglobulin CDR3-like region of the CD4 molecule inhibits provirus transcription in HIV-infected T cells. EMBO J. 1993 Dec 15;12(13):4909–4921. doi: 10.1002/j.1460-2075.1993.tb06185.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Benkirane M., Hirn M., Carrière D., Devaux C. Functional epitope analysis of the human CD4 molecule: antibodies that inhibit human immunodeficiency virus type 1 gene expression bind to the immunoglobulin CDR3-like region of CD4. J Virol. 1995 Nov;69(11):6898–6903. doi: 10.1128/jvi.69.11.6898-6903.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Benkirane M., Jeang K. T., Devaux C. The cytoplasmic domain of CD4 plays a critical role during the early stages of HIV infection in T-cells. EMBO J. 1994 Dec 1;13(23):5559–5569. doi: 10.1002/j.1460-2075.1994.tb06893.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Benkirane M., Schmid-Antomarchi H., Littman D. R., Hirn M., Rossi B., Devaux C. The cytoplasmic tail of CD4 is required for inhibition of human immunodeficiency virus type 1 replication by antibodies that bind to the immunoglobulin CDR3-like region in domain 1 of CD4. J Virol. 1995 Nov;69(11):6904–6910. doi: 10.1128/jvi.69.11.6904-6910.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Chomczynski P., Sacchi N. Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem. 1987 Apr;162(1):156–159. doi: 10.1006/abio.1987.9999. [DOI] [PubMed] [Google Scholar]
  9. Clapham P. R., Blanc D., Weiss R. A. Specific cell surface requirements for the infection of CD4-positive cells by human immunodeficiency virus types 1 and 2 and by Simian immunodeficiency virus. Virology. 1991 Apr;181(2):703–715. doi: 10.1016/0042-6822(91)90904-P. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Corbeau P., Benkirane M., Weil R., David C., Emiliani S., Olive D., Mawas C., Serre A., Devaux C. Ig CDR3-like region of the CD4 molecule is involved in HIV-induced syncytia formation but not in viral entry. J Immunol. 1993 Jan 1;150(1):290–301. [PubMed] [Google Scholar]
  11. Corbeau P., Devaux C., Kourilsky F., Chermann J. C. An early postinfection signal mediated by monoclonal anti-beta 2 microglobulin antibody is responsible for delayed production of human immunodeficiency virus type 1 in peripheral blood mononuclear cells. J Virol. 1990 Apr;64(4):1459–1464. doi: 10.1128/jvi.64.4.1459-1464.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Corbeau P., Olive D., Devaux C. Anti-HLA antigen class I heavy chain monoclonal antibodies inhibit human immunodeficiency virus production by peripheral blood mononuclear cells. Eur J Immunol. 1991 Apr;21(4):865–871. doi: 10.1002/eji.1830210402. [DOI] [PubMed] [Google Scholar]
  13. Dalgleish A. G., Beverley P. C., Clapham P. R., Crawford D. H., Greaves M. F., Weiss R. A. The CD4 (T4) antigen is an essential component of the receptor for the AIDS retrovirus. Nature. 1984 Dec 20;312(5996):763–767. doi: 10.1038/312763a0. [DOI] [PubMed] [Google Scholar]
  14. Dasgupta J. D., Cemach K., Dubey D. P., Yunis E. J., Amos D. B. The role of class I histocompatibility antigens in the regulation of T-cell activation. Proc Natl Acad Sci U S A. 1987 Feb;84(4):1094–1098. doi: 10.1073/pnas.84.4.1094. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Devaux C., Boucraut J., Poirier G., Corbeau P., Rey F., Benkirane M., Perarnau B., Kourilsky F., Chermann J. C. Anti-beta 2-microglobulin monoclonal antibodies mediate a delay in HIV1 cytopathic effect on MT4 cells. Res Immunol. 1990 May-Jun;141(4-5):357–372. doi: 10.1016/0923-2494(90)90026-u. [DOI] [PubMed] [Google Scholar]
  16. Dimitrov D. S., Broder C. C., Berger E. A., Blumenthal R. Calcium ions are required for cell fusion mediated by the CD4-human immunodeficiency virus type 1 envelope glycoprotein interaction. J Virol. 1993 Mar;67(3):1647–1652. doi: 10.1128/jvi.67.3.1647-1652.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Dimitrov D. S., Willey R. L., Sato H., Chang L. J., Blumenthal R., Martin M. A. Quantitation of human immunodeficiency virus type 1 infection kinetics. J Virol. 1993 Apr;67(4):2182–2190. doi: 10.1128/jvi.67.4.2182-2190.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Geppert T. D., Wacholtz M. C., Patel S. S., Lightfoot E., Lipsky P. E. Activation of human T cell clones and Jurkat cells by cross-linking class I MHC molecules. J Immunol. 1989 Jun 1;142(11):3763–3772. [PubMed] [Google Scholar]
  19. Gomez M. B., Hildreth J. E. Antibody to adhesion molecule LFA-1 enhances plasma neutralization of human immunodeficiency virus type 1. J Virol. 1995 Aug;69(8):4628–4632. doi: 10.1128/jvi.69.8.4628-4632.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Grassi F., Meneveri R., Gullberg M., Lopalco L., Rossi G. B., Lanza P., De Santis C., Brattsand G., Buttò S., Ginelli E. Human immunodeficiency virus type 1 gp120 mimics a hidden monomorphic epitope borne by class I major histocompatibility complex heavy chains. J Exp Med. 1991 Jul 1;174(1):53–62. doi: 10.1084/jem.174.1.53. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Hildreth J. E., Orentas R. J. Involvement of a leukocyte adhesion receptor (LFA-1) in HIV-induced syncytium formation. Science. 1989 Jun 2;244(4908):1075–1078. doi: 10.1126/science.2543075. [DOI] [PubMed] [Google Scholar]
  22. Hu W. S., Temin H. M. Retroviral recombination and reverse transcription. Science. 1990 Nov 30;250(4985):1227–1233. doi: 10.1126/science.1700865. [DOI] [PubMed] [Google Scholar]
  23. Huet S., Boumsell L., Raynal B., Degos L., Dausset J., Bernard A. Role in T-cell activation for HLA class I molecules from accessory cells: further distinction between activation signals delivered to T cells via CD2 and CD3 molecules. Proc Natl Acad Sci U S A. 1987 Oct;84(20):7222–7226. doi: 10.1073/pnas.84.20.7222. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Klatzmann D., Barré-Sinoussi F., Nugeyre M. T., Danquet C., Vilmer E., Griscelli C., Brun-Veziret F., Rouzioux C., Gluckman J. C., Chermann J. C. Selective tropism of lymphadenopathy associated virus (LAV) for helper-inducer T lymphocytes. Science. 1984 Jul 6;225(4657):59–63. doi: 10.1126/science.6328660. [DOI] [PubMed] [Google Scholar]
  25. Lemasson I., Briant L., Hague B., Coudronnière N., Heron L., David C., Rebouissou C., Kindt T., Devaux C. An antibody that binds domain 1 of CD4 inhibits replication of HIV-1, but not HTLV-I, in a CD4-positive/p56lck-negative HTLV-I-transformed cell line. J Immunol. 1996 Jan 15;156(2):859–865. [PubMed] [Google Scholar]
  26. Markovitz D. M., Smith M. J., Hilfinger J., Hannibal M. C., Petryniak B., Nabel G. J. Activation of the human immunodeficiency virus type 2 enhancer is dependent on purine box and kappa B regulatory elements. J Virol. 1992 Sep;66(9):5479–5484. doi: 10.1128/jvi.66.9.5479-5484.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. McDougal J. S., Nicholson J. K., Cross G. D., Cort S. P., Kennedy M. S., Mawle A. C. Binding of the human retrovirus HTLV-III/LAV/ARV/HIV to the CD4 (T4) molecule: conformation dependence, epitope mapping, antibody inhibition, and potential for idiotypic mimicry. J Immunol. 1986 Nov 1;137(9):2937–2944. [PubMed] [Google Scholar]
  28. 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]
  29. Rudd C. E., Trevillyan J. M., Dasgupta J. D., Wong L. L., Schlossman S. F. The CD4 receptor is complexed in detergent lysates to a protein-tyrosine kinase (pp58) from human T lymphocytes. Proc Natl Acad Sci U S A. 1988 Jul;85(14):5190–5194. doi: 10.1073/pnas.85.14.5190. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Sato A. I., Balamuth F. B., Ugen K. E., Williams W. V., Weiner D. B. Identification of CD7 glycoprotein as an accessory molecule in HIV-1-mediated syncytium formation and cellfree infection. J Immunol. 1994 May 15;152(10):5142–5152. [PubMed] [Google Scholar]
  31. Sommerfelt M. A., Asjö B. Intercellular adhesion molecule 3, a candidate human immunodeficiency virus type 1 co-receptor on lymphoid and monocytoid cells. J Gen Virol. 1995 Jun;76(Pt 6):1345–1352. doi: 10.1099/0022-1317-76-6-1345. [DOI] [PubMed] [Google Scholar]
  32. Sterkers G., Henin Y., Kalil J., Bagot M., Levy J. P. Influence of HLA class I- and class II-specific monoclonal antibodies on DR-restricted lymphoproliferative responses. I. Unseparated populations of effector cells. J Immunol. 1983 Dec;131(6):2735–2740. [PubMed] [Google Scholar]
  33. Stevenson M., Haggerty S., Lamonica C. A., Meier C. M., Welch S. K., Wasiak A. J. Integration is not necessary for expression of human immunodeficiency virus type 1 protein products. J Virol. 1990 May;64(5):2421–2425. doi: 10.1128/jvi.64.5.2421-2425.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Stevenson M., Stanwick T. L., Dempsey M. P., Lamonica C. A. HIV-1 replication is controlled at the level of T cell activation and proviral integration. EMBO J. 1990 May;9(5):1551–1560. doi: 10.1002/j.1460-2075.1990.tb08274.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Turco M. C., De Felice M., Corbo L., Morrone G., Mertelsmann R., Ferrone S., Venuta S. Regulatory role of a monomorphic determinant of HLA Class I antigens in T cell proliferation. J Immunol. 1985 Oct;135(4):2268–2273. [PubMed] [Google Scholar]
  36. Valentin A., Lundin K., Patarroyo M., Asjö B. The leukocyte adhesion glycoprotein CD18 participates in HIV-1-induced syncytia formation in monocytoid and T cells. J Immunol. 1990 Feb 1;144(3):934–937. [PubMed] [Google Scholar]
  37. Zack J. A., Arrigo S. J., Weitsman S. R., Go A. S., Haislip A., Chen I. S. HIV-1 entry into quiescent primary lymphocytes: molecular analysis reveals a labile, latent viral structure. Cell. 1990 Apr 20;61(2):213–222. doi: 10.1016/0092-8674(90)90802-l. [DOI] [PubMed] [Google Scholar]
  38. Zack J. A., Haislip A. M., Krogstad P., Chen I. S. Incompletely reverse-transcribed human immunodeficiency virus type 1 genomes in quiescent cells can function as intermediates in the retroviral life cycle. J Virol. 1992 Mar;66(3):1717–1725. doi: 10.1128/jvi.66.3.1717-1725.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]

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