• We are sorry, but NCBI web applications do not support your browser and may not function properly. More information
Logo of pnasPNASInfo for AuthorsSubscriptionsAboutThis Article
Proc Natl Acad Sci U S A. Oct 1985; 82(20): 7096–7100.
PMCID: PMC391317

3'-Azido-3'-deoxythymidine (BW A509U): an antiviral agent that inhibits the infectivity and cytopathic effect of human T-lymphotropic virus type III/lymphadenopathy-associated virus in vitro.


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

Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (991K), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References.

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Gottlieb MS, Schroff R, Schanker HM, Weisman JD, Fan PT, Wolf RA, 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. [PubMed]
  • Masur H, Michelis MA, Greene JB, Onorato I, Stouwe RA, Holzman RS, Wormser G, Brettman L, Lange M, Murray HW, et al. 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. [PubMed]
  • Siegal FP, Lopez C, Hammer GS, Brown AE, Kornfeld SJ, Gold J, Hassett J, Hirschman SZ, Cunningham-Rundles C, Adelsberg BR, et al. 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. [PubMed]
  • Francis DP, Curran JW, Essex M. Epidemic acquired immune deficiency syndrome: epidemiologic evidence for a transmissible agent. J Natl Cancer Inst. 1983 Jul;71(1):1–4. [PubMed]
  • Broder S, Gallo RC. A pathogenic retrovirus (HTLV-III) linked to AIDS. N Engl J Med. 1984 Nov 15;311(20):1292–1297. [PubMed]
  • Shaw GM, Harper ME, Hahn BH, Epstein LG, Gajdusek DC, Price RW, Navia BA, Petito CK, O'Hara CJ, Groopman JE, et al. HTLV-III infection in brains of children and adults with AIDS encephalopathy. Science. 1985 Jan 11;227(4683):177–182. [PubMed]
  • Feorino PM, Jaffe HW, Palmer E, Peterman TA, Francis DP, Kalyanaraman VS, Weinstein RA, Stoneburner RL, Alexander WJ, Raevsky C, et al. Transfusion-associated acquired immunodeficiency syndrome. Evidence for persistent infection in blood donors. N Engl J Med. 1985 May 16;312(20):1293–1296. [PubMed]
  • Popovic M, Sarngadharan MG, Read E, Gallo RC. 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. [PubMed]
  • Gallo RC, Salahuddin SZ, Popovic M, Shearer GM, Kaplan M, Haynes BF, Palker TJ, Redfield R, Oleske J, Safai B, et al. 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. [PubMed]
  • Schüpbach J, Popovic M, Gilden RV, Gonda MA, Sarngadharan MG, Gallo RC. Serological analysis of a subgroup of human T-lymphotropic retroviruses (HTLV-III) associated with AIDS. Science. 1984 May 4;224(4648):503–505. [PubMed]
  • Sarngadharan MG, Popovic M, Bruch L, Schüpbach J, Gallo RC. Antibodies reactive with human T-lymphotropic retroviruses (HTLV-III) in the serum of patients with AIDS. Science. 1984 May 4;224(4648):506–508. [PubMed]
  • Barré-Sinoussi F, Chermann JC, Rey F, Nugeyre MT, Chamaret S, Gruest J, Dauguet C, Axler-Blin C, Vézinet-Brun F, Rouzioux C, et al. 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. [PubMed]
  • Klatzmann D, Barré-Sinoussi F, Nugeyre MT, Danquet C, Vilmer E, Griscelli C, Brun-Veziret F, Rouzioux C, Gluckman JC, Chermann JC, et al. Selective tropism of lymphadenopathy associated virus (LAV) for helper-inducer T lymphocytes. Science. 1984 Jul 6;225(4657):59–63. [PubMed]
  • Brun-Vézinet F, Rouzioux C, Montagnier L, Chamaret S, Gruest J, Barré-Sinoussi F, Geroldi D, Chermann JC, McCormick J, Mitchell S, et al. Prevalence of antibodies to lymphadenopathy-associated retrovirus in African patients with AIDS. Science. 1984 Oct 26;226(4673):453–456. [PubMed]
  • De Clercq E. Suramin: a potent inhibitor of the reverse transcriptase of RNA tumor viruses. Cancer Lett. 1979 Nov;8(1):9–22. [PubMed]
  • Mitsuya H, Popovic M, Yarchoan R, Matsushita S, Gallo RC, 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. [PubMed]
  • Mitsuya H, Matsushita S, Harper ME, Broder S. Pharmacological inhibition of infectivity of HTLV-III in vitro. Cancer Res. 1985 Sep;45(9 Suppl):4583s–4587s. [PubMed]
  • Rozenbaum W, Dormont D, Spire B, Vilmer E, Gentilini M, Griscelli C, Montagnier L, Barre-Sinoussi F, Chermann JC. Antimoniotungstate (HPA 23) treatment of three patients with AIDS and one with prodrome. Lancet. 1985 Feb 23;1(8426):450–451. [PubMed]
  • McCormick JB, Getchell JP, Mitchell SW, Hicks DR. Ribavirin suppresses replication of lymphadenopathy-associated virus in cultures of human adult T lymphocytes. Lancet. 1984 Dec 15;2(8416):1367–1369. [PubMed]
  • Ho DD, Hartshorn KL, Rota TR, Andrews CA, Kaplan JC, Schooley RT, Hirsch MS. Recombinant human interferon alfa-A suppresses HTLV-III replication in vitro. Lancet. 1985 Mar 16;1(8429):602–604. [PubMed]
  • Sandstrom EG, Kaplan JC, Byington RE, Hirsch MS. Inhibition of human T-cell lymphotropic virus type III in vitro by phosphonoformate. Lancet. 1985 Jun 29;1(8444):1480–1482. [PubMed]
  • Hahn BH, Gonda MA, Shaw GM, Popovic M, Hoxie JA, Gallo RC, 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. [PMC free article] [PubMed]
  • Lin TS, Prusoff WH. Synthesis and biological activity of several amino analogues of thymidine. J Med Chem. 1978 Jan;21(1):109–112. [PubMed]
  • Mitsuya H, Guo HG, Cossman J, Megson M, Reitz MS, 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. [PubMed]
  • Popovic M, Sarin PS, Robert-Gurroff M, Kalyanaraman VS, Mann D, Minowada J, Gallo RC. Isolation and transmission of human retrovirus (human t-cell leukemia virus). Science. 1983 Feb 18;219(4586):856–859. [PubMed]
  • di Marzo Veronese F, Sarngadharan MG, Rahman R, Markham PD, Popovic M, Bodner AJ, Gallo RC. 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. [PMC free article] [PubMed]
  • 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]
  • Yarchoan R, Tosato G, Blaese RM, Simon RM, Nelson DL. Limiting dilution analysis of Epstein-Barr virus-induced immunoglobulin production by human B cells. J Exp Med. 1983 Jan 1;157(1):1–14. [PMC free article] [PubMed]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences


Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...


  • Cited in Books
    Cited in Books
    PubMed Central articles cited in books
  • Compound
    PubChem Compound links
  • MedGen
    Related information in MedGen
  • PubMed
    PubMed citations for these articles
  • Substance
    PubChem Substance links

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...