Abstract
The acquired immune deficiency syndrome (AIDS) is thought to result from infection of T cells by a pathogenic human retrovirus, human T-lymphotropic virus type III (HTLV-III) or lymphadenopathy-associated virus (LAV). In this report, we describe the antiviral effects of a thymidine analogue,3'-azido-3'-deoxythymidine (BW A509U), which, as a triphosphate, inhibits the reverse transcriptase of HTLV-III/LAV. This agent blocks the expression of the p24 gag protein of HTLV-III/LAV in H9 cells following exposure to virus. The drug also inhibits the cytopathic effect of HTLV-IIIB (a virus derived from a pool of American patients) and HTLV-III/RF-II (an isolate obtained from a Haitian patient that differs by about 20% in the amino acid sequence of the envelope gene from several isolates of HTLV-III/LAV, including HTLV-IIIB, analyzed so far). 3'-Azido-3'-deoxythymidine also completely blocks viral replication as assessed by reverse transcriptase production in normal human peripheral blood mononuclear cells exposed to HTLV-IIIB. Finally, at concentrations of 3'-azido-3'-deoxythymidine that block the in vitro infectivity and cytopathic effect of HTLV-IIIB, the in vitro immune functions of normal T cells remain basically intact.
Full text
PDF




Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- 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]
- Broder S., Gallo R. C. A pathogenic retrovirus (HTLV-III) linked to AIDS. N Engl J Med. 1984 Nov 15;311(20):1292–1297. doi: 10.1056/NEJM198411153112006. [DOI] [PubMed] [Google Scholar]
- Brun-Vézinet F., Rouzioux C., Montagnier L., Chamaret S., Gruest J., Barré-Sinoussi F., Geroldi D., Chermann J. C., McCormick J., Mitchell S. Prevalence of antibodies to lymphadenopathy-associated retrovirus in African patients with AIDS. Science. 1984 Oct 26;226(4673):453–456. doi: 10.1126/science.6238406. [DOI] [PubMed] [Google Scholar]
- De Clercq E. Suramin: a potent inhibitor of the reverse transcriptase of RNA tumor viruses. Cancer Lett. 1979 Nov;8(1):9–22. doi: 10.1016/0304-3835(79)90017-x. [DOI] [PubMed] [Google Scholar]
- Feorino P. M., Jaffe H. W., Palmer E., Peterman T. A., Francis D. P., Kalyanaraman V. S., Weinstein R. A., Stoneburner R. L., Alexander W. J., Raevsky C. Transfusion-associated acquired immunodeficiency syndrome. Evidence for persistent infection in blood donors. N Engl J Med. 1985 May 16;312(20):1293–1296. doi: 10.1056/NEJM198505163122005. [DOI] [PubMed] [Google Scholar]
- Francis D. P., Curran J. W., Essex M. Epidemic acquired immune deficiency syndrome: epidemiologic evidence for a transmissible agent. J Natl Cancer Inst. 1983 Jul;71(1):1–4. [PubMed] [Google Scholar]
- Gallo R. C., Salahuddin S. Z., Popovic M., Shearer G. M., Kaplan M., Haynes B. F., Palker T. J., Redfield R., Oleske J., Safai B. Frequent detection and isolation of cytopathic retroviruses (HTLV-III) from patients with AIDS and at risk for AIDS. Science. 1984 May 4;224(4648):500–503. doi: 10.1126/science.6200936. [DOI] [PubMed] [Google Scholar]
- Gottlieb M. S., Schroff R., Schanker H. M., Weisman J. D., Fan P. T., Wolf R. A., Saxon A. Pneumocystis carinii pneumonia and mucosal candidiasis in previously healthy homosexual men: evidence of a new acquired cellular immunodeficiency. N Engl J Med. 1981 Dec 10;305(24):1425–1431. doi: 10.1056/NEJM198112103052401. [DOI] [PubMed] [Google Scholar]
- Hahn B. H., Gonda M. A., Shaw G. M., Popovic M., Hoxie J. A., Gallo R. C., Wong-Staal F. Genomic diversity of the acquired immune deficiency syndrome virus HTLV-III: different viruses exhibit greatest divergence in their envelope genes. Proc Natl Acad Sci U S A. 1985 Jul;82(14):4813–4817. doi: 10.1073/pnas.82.14.4813. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ho D. D., Hartshorn K. L., Rota T. R., Andrews C. A., Kaplan J. C., Schooley R. T., Hirsch M. S. Recombinant human interferon alfa-A suppresses HTLV-III replication in vitro. Lancet. 1985 Mar 16;1(8429):602–604. doi: 10.1016/s0140-6736(85)92144-0. [DOI] [PubMed] [Google Scholar]
- 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]
- Lin T. S., Prusoff W. H. Synthesis and biological activity of several amino analogues of thymidine. J Med Chem. 1978 Jan;21(1):109–112. [PubMed] [Google Scholar]
- Masur H., Michelis M. A., Greene J. B., Onorato I., Stouwe R. A., Holzman R. S., Wormser G., Brettman L., Lange M., Murray H. W. An outbreak of community-acquired Pneumocystis carinii pneumonia: initial manifestation of cellular immune dysfunction. N Engl J Med. 1981 Dec 10;305(24):1431–1438. doi: 10.1056/NEJM198112103052402. [DOI] [PubMed] [Google Scholar]
- McCormick J. B., Getchell J. P., Mitchell S. W., Hicks D. R. Ribavirin suppresses replication of lymphadenopathy-associated virus in cultures of human adult T lymphocytes. Lancet. 1984 Dec 15;2(8416):1367–1369. doi: 10.1016/s0140-6736(84)92060-9. [DOI] [PubMed] [Google Scholar]
- Mitsuya H., Guo H. G., Cossman J., Megson M., Reitz M. S., Jr, Broder S. Functional properties of antigen-specific T cells infected by human T-cell leukemia-lymphoma virus (HTLV-I). Science. 1984 Sep 28;225(4669):1484–1486. doi: 10.1126/science.6206569. [DOI] [PubMed] [Google Scholar]
- Mitsuya H., Matsushita S., Harper M. E., Broder S. Pharmacological inhibition of infectivity of HTLV-III in vitro. Cancer Res. 1985 Sep;45(9 Suppl):4583s–4587s. [PubMed] [Google Scholar]
- Mitsuya H., Osaki K., Tomino S., Katsuki T., Kishimoto S. Pathophysiologic analysis of peripheral blood lymphocytes from patients with primary immunodeficiency. I. Ig synthesis by peripheral blood lymphocytes stimulated with either pokeweed mitogen or Epstein-Barr virus in vitro. J Immunol. 1981 Jul;127(1):311–315. [PubMed] [Google Scholar]
- Mitsuya H., Popovic M., Yarchoan R., Matsushita S., Gallo R. C., Broder S. Suramin protection of T cells in vitro against infectivity and cytopathic effect of HTLV-III. Science. 1984 Oct 12;226(4671):172–174. doi: 10.1126/science.6091268. [DOI] [PubMed] [Google Scholar]
- Popovic M., Sarin P. S., Robert-Gurroff M., Kalyanaraman V. S., Mann D., Minowada J., Gallo R. C. Isolation and transmission of human retrovirus (human t-cell leukemia virus). Science. 1983 Feb 18;219(4586):856–859. doi: 10.1126/science.6600519. [DOI] [PubMed] [Google Scholar]
- Popovic M., Sarngadharan M. G., Read E., Gallo R. C. Detection, isolation, and continuous production of cytopathic retroviruses (HTLV-III) from patients with AIDS and pre-AIDS. Science. 1984 May 4;224(4648):497–500. doi: 10.1126/science.6200935. [DOI] [PubMed] [Google Scholar]
- Rozenbaum W., Dormont D., Spire B., Vilmer E., Gentilini M., Griscelli C., Montagnier L., Barre-Sinoussi F., Chermann J. C. Antimoniotungstate (HPA 23) treatment of three patients with AIDS and one with prodrome. Lancet. 1985 Feb 23;1(8426):450–451. doi: 10.1016/s0140-6736(85)91162-6. [DOI] [PubMed] [Google Scholar]
- Sandstrom E. G., Kaplan J. C., Byington R. E., Hirsch M. S. Inhibition of human T-cell lymphotropic virus type III in vitro by phosphonoformate. Lancet. 1985 Jun 29;1(8444):1480–1482. doi: 10.1016/s0140-6736(85)92255-x. [DOI] [PubMed] [Google Scholar]
- Sarngadharan M. G., Popovic M., Bruch L., Schüpbach J., Gallo R. C. Antibodies reactive with human T-lymphotropic retroviruses (HTLV-III) in the serum of patients with AIDS. Science. 1984 May 4;224(4648):506–508. doi: 10.1126/science.6324345. [DOI] [PubMed] [Google Scholar]
- Schüpbach J., Popovic M., Gilden R. V., Gonda M. A., Sarngadharan M. G., Gallo R. C. Serological analysis of a subgroup of human T-lymphotropic retroviruses (HTLV-III) associated with AIDS. Science. 1984 May 4;224(4648):503–505. doi: 10.1126/science.6200937. [DOI] [PubMed] [Google Scholar]
- Shaw G. M., Harper M. E., Hahn B. H., Epstein L. G., Gajdusek D. C., Price R. W., Navia B. A., Petito C. K., O'Hara C. J., Groopman J. E. HTLV-III infection in brains of children and adults with AIDS encephalopathy. Science. 1985 Jan 11;227(4683):177–182. doi: 10.1126/science.2981429. [DOI] [PubMed] [Google Scholar]
- Siegal F. P., Lopez C., Hammer G. S., Brown A. E., Kornfeld S. J., Gold J., Hassett J., Hirschman S. Z., Cunningham-Rundles C., Adelsberg B. R. Severe acquired immunodeficiency in male homosexuals, manifested by chronic perianal ulcerative herpes simplex lesions. N Engl J Med. 1981 Dec 10;305(24):1439–1444. doi: 10.1056/NEJM198112103052403. [DOI] [PubMed] [Google Scholar]
- Yarchoan R., Tosato G., Blaese R. M., Simon R. M., Nelson D. L. Limiting dilution analysis of Epstein-Barr virus-induced immunoglobulin production by human B cells. J Exp Med. 1983 Jan 1;157(1):1–14. doi: 10.1084/jem.157.1.1. [DOI] [PMC free article] [PubMed] [Google Scholar]
- di Marzo Veronese F., Sarngadharan M. G., Rahman R., Markham P. D., Popovic M., Bodner A. J., Gallo R. C. Monoclonal antibodies specific for p24, the major core protein of human T-cell leukemia virus type III. Proc Natl Acad Sci U S A. 1985 Aug;82(15):5199–5202. doi: 10.1073/pnas.82.15.5199. [DOI] [PMC free article] [PubMed] [Google Scholar]