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. 1994 May;38(5):986–990. doi: 10.1128/aac.38.5.986

Effect of 3'-azido-3'-deoxythymidine and 2',3'-dideoxyinosine on establishment of human immunodeficiency virus type 1 infection in cultured CD8+ lymphocytes.

L Mercure 1, B J Brenner 1, D Phaneuf 1, C Tsoukas 1, M A Wainberg 1
PMCID: PMC188138  PMID: 8067781

Abstract

Several groups have shown that peripheral CD8+ lymphocytes can be infected with human immunodeficiency virus type 1 (HIV-1), resulting in noncytopathic infection and persistent production of viral particles. We studied the ability of 3'-azido-3'-deoxythymidine (AZT) and 2',3'-dideoxyinosine (ddI) to inhibit the establishment of HIV-1 infection in CD8+ cells that were derived from cultures of peripheral blood lymphocytes exposed to both virus and drug. In situ infection of CD8+ cells was demonstrated by double flow cytometry analysis by using both anti-glycoprotein 120 (anti-gp120) and anti-CD8 monoclonal antibodies. At higher concentrations of drug (e.g., 0.4 microM AZT), the production of viral particles was inhibited for over 2 months, as assessed by p24 antigen levels in the culture medium. We also performed a time course experiment to determine whether HIV-1 infection of CD8+ cells would be affected by treatment of peripheral blood lymphocytes with AZT or ddI for different intervals following exposure to virus. Quantitative PCR revealed that 0.4 microM AZT, added as late as 24 h after infection, interfered with the formation of proviral DNA in CD8+ cells. Both HIV-1 load and the production of progeny virions by CD8+ cells, as monitored by reverse transcriptase activity in culture fluids, were inhibited by both AZT and ddI in a dose-dependent manner.

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Selected References

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  1. Adachi A., Koenig S., Gendelman H. E., Daugherty D., Gattoni-Celli S., Fauci A. S., Martin M. A. Productive, persistent infection of human colorectal cell lines with human immunodeficiency virus. J Virol. 1987 Jan;61(1):209–213. doi: 10.1128/jvi.61.1.209-213.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Brinchmann J. E., Gaudernack G., Vartdal F. CD8+ T cells inhibit HIV replication in naturally infected CD4+ T cells. Evidence for a soluble inhibitor. J Immunol. 1990 Apr 15;144(8):2961–2966. [PubMed] [Google Scholar]
  3. Cao Y. Z., Friedman-Kien A. E., Huang Y. X., Li X. L., Mirabile M., Moudgil T., Zucker-Franklin D., Ho D. D. CD4-independent, productive human immunodeficiency virus type 1 infection of hepatoma cell lines in vitro. J Virol. 1990 Jun;64(6):2553–2559. doi: 10.1128/jvi.64.6.2553-2559.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Cheynier R., Soulha M., Laure F., Vol J. C., Reveil B., Gallo R. C., Sarin P. S., Zagury D. HIV-1 expression by T8 lymphocytes after transfection. AIDS Res Hum Retroviruses. 1988 Feb;4(1):43–50. doi: 10.1089/aid.1988.4.43. [DOI] [PubMed] [Google Scholar]
  5. Dahl K., Martin K., Miller G. Differences among human immunodeficiency virus strains in their capacities to induce cytolysis or persistent infection of a lymphoblastoid cell line immortalized by Epstein-Barr virus. J Virol. 1987 May;61(5):1602–1608. doi: 10.1128/jvi.61.5.1602-1608.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. De Maria A., Pantaleo G., Schnittman S. M., Greenhouse J. J., Baseler M., Orenstein J. M., Fauci A. S. Infection of CD8+ T lymphocytes with HIV. Requirement for interaction with infected CD4+ cells and induction of infectious virus from chronically infected CD8+ cells. J Immunol. 1991 Apr 1;146(7):2220–2226. [PubMed] [Google Scholar]
  7. De Rossi A., Franchini G., Aldovini A., Del Mistro A., Chieco-Bianchi L., Gallo R. C., Wong-Staal F. Differential response to the cytopathic effects of human T-cell lymphotropic virus type III (HTLV-III) superinfection in T4+ (helper) and T8+ (suppressor) T-cell clones transformed by HTLV-I. Proc Natl Acad Sci U S A. 1986 Jun;83(12):4297–4301. doi: 10.1073/pnas.83.12.4297. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Folks T. M., Kessler S. W., Orenstein J. M., Justement J. S., Jaffe E. S., Fauci A. S. Infection and replication of HIV-1 in purified progenitor cells of normal human bone marrow. Science. 1988 Nov 11;242(4880):919–922. doi: 10.1126/science.2460922. [DOI] [PubMed] [Google Scholar]
  9. Freedman A. R., Gibson F. M., Fleming S. C., Spry C. J., Griffin G. E. Human immunodeficiency virus infection of eosinophils in human bone marrow cultures. J Exp Med. 1991 Dec 1;174(6):1661–1664. doi: 10.1084/jem.174.6.1661. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Gendelman H. E., Orenstein J. M., Baca L. M., Weiser B., Burger H., Kalter D. C., Meltzer M. S. The macrophage in the persistence and pathogenesis of HIV infection. AIDS. 1989 Aug;3(8):475–495. doi: 10.1097/00002030-198908000-00001. [DOI] [PubMed] [Google Scholar]
  11. Hatch W. C., Tanaka K. E., Calvelli T., Rashbaum W. K., Kress Y., Lyman W. D. Persistent productive HIV-1 infection of a CD4- human fetal thymocyte line. J Immunol. 1992 May 15;148(10):3055–3061. [PubMed] [Google Scholar]
  12. Langhoff E., Terwilliger E. F., Bos H. J., Kalland K. H., Poznansky M. C., Bacon O. M., Haseltine W. A. Replication of human immunodeficiency virus type 1 in primary dendritic cell cultures. Proc Natl Acad Sci U S A. 1991 Sep 15;88(18):7998–8002. doi: 10.1073/pnas.88.18.7998. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Li X. L., Moudgil T., Vinters H. V., Ho D. D. CD4-independent, productive infection of a neuronal cell line by human immunodeficiency virus type 1. J Virol. 1990 Mar;64(3):1383–1387. doi: 10.1128/jvi.64.3.1383-1387.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Mercure L., Phaneuf D., Wainberg M. A. Detection of unintegrated human immunodeficiency virus type 1 DNA in persistently infected CD8+ cells. J Gen Virol. 1993 Oct;74(Pt 10):2077–2083. doi: 10.1099/0022-1317-74-10-2077. [DOI] [PubMed] [Google Scholar]
  15. Monroe J. E., Calender A., Mulder C. Epstein-Barr virus-positive and -negative B-cell lines can be infected with human immunodeficiency virus types 1 and 2. J Virol. 1988 Sep;62(9):3497–3500. doi: 10.1128/jvi.62.9.3497-3500.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Nicholson J. K., Cross G. D., Callaway C. S., McDougal J. S. In vitro infection of human monocytes with human T lymphotropic virus type III/lymphadenopathy-associated virus (HTLV-III/LAV). J Immunol. 1986 Jul 1;137(1):323–329. [PubMed] [Google Scholar]
  17. Nixon D. F., McMichael A. J. Cytotoxic T-cell recognition of HIV proteins and peptides. AIDS. 1991 Sep;5(9):1049–1059. [PubMed] [Google Scholar]
  18. Ou C. Y., Kwok S., Mitchell S. W., Mack D. H., Sninsky J. J., Krebs J. W., Feorino P., Warfield D., Schochetman G. DNA amplification for direct detection of HIV-1 in DNA of peripheral blood mononuclear cells. Science. 1988 Jan 15;239(4837):295–297. doi: 10.1126/science.3336784. [DOI] [PubMed] [Google Scholar]
  19. Tsubota H., Ringler D. J., Kannagi M., King N. W., Solomon K. R., MacKey J. J., Walsh D. G., Letvin N. L. CD8+CD4- lymphocyte lines can harbor the AIDS virus in vitro. J Immunol. 1989 Aug 1;143(3):858–863. [PubMed] [Google Scholar]
  20. Walker B. D., Plata F. Cytotoxic T lymphocytes against HIV. AIDS. 1990 Mar;4(3):177–184. doi: 10.1097/00002030-199003000-00001. [DOI] [PubMed] [Google Scholar]
  21. Walker C. M., Moody D. J., Stites D. P., Levy J. A. CD8+ lymphocytes can control HIV infection in vitro by suppressing virus replication. Science. 1986 Dec 19;234(4783):1563–1566. doi: 10.1126/science.2431484. [DOI] [PubMed] [Google Scholar]
  22. Yarchoan R., Pluda J. M., Perno C. F., Mitsuya H., Broder S. Anti-retroviral therapy of human immunodeficiency virus infection: current strategies and challenges for the future. Blood. 1991 Aug 15;78(4):859–884. [PubMed] [Google Scholar]

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