Home LiteratureArticle Details
PMID: 2413459 Published · ppublish English Journal Article

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.

Mitsuya H, Weinhold KJ, Furman PA, St Clair MH, Lehrman SN, Gallo RC, Bolognesi D, Barry DW, Broder S

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.

MeSH Terms
Acquired Immunodeficiency Syndrome/microbiology Antiviral Agents/pharmacology Deltaretrovirus/drug effects,genetics,pathogenicity Gene Products, gag Humans RNA-Directed DNA Polymerase/metabolism Retroviridae Proteins/genetics Thymidine/analogs & derivatives,pharmacology Transcription, Genetic/drug effects Zidovudine
Chemicals
Antiviral Agents Gene Products, gag Retroviridae Proteins Zidovudine RNA-Directed DNA Polymerase Thymidine
Authors & Affiliations
9 authors, click to expand affiliations / ORCID
Mitsuya H
Weinhold K J
Furman P A
St Clair M H
Lehrman S N
Gallo R C
Bolognesi D
Barry D W
Broder S
References (28)
28 references, click to expand
  1. Frequent detection and isolation of cytopathic retroviruses (HTLV-III) from patients with AIDS and at risk for AIDS.
    Science. 1984 May 4;224(4648):500-3 PMID: 6200936
  2. 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 PMID: 6200935
  3. Antibodies reactive with human T-lymphotropic retroviruses (HTLV-III) in the serum of patients with AIDS.
    Science. 1984 May 4;224(4648):506-8 PMID: 6324345
  4. Selective tropism of lymphadenopathy associated virus (LAV) for helper-inducer T lymphocytes.
    Science. 1984 Jul 6;225(4657):59-63 PMID: 6328660
  5. Functional properties of antigen-specific T cells infected by human T-cell leukemia-lymphoma virus (HTLV-I).
    Science. 1984 Sep 28;225(4669):1484-6 PMID: 6206569
  6. Suramin protection of T cells in vitro against infectivity and cytopathic effect of HTLV-III.
    Science. 1984 Oct 12;226(4671):172-4 PMID: 6091268
  7. A pathogenic retrovirus (HTLV-III) linked to AIDS.
    N Engl J Med. 1984 Nov 15;311(20):1292-7 PMID: 6208484
  8. Prevalence of antibodies to lymphadenopathy-associated retrovirus in African patients with AIDS.
    Science. 1984 Oct 26;226(4673):453-6 PMID: 6238406
  9. Ribavirin suppresses replication of lymphadenopathy-associated virus in cultures of human adult T lymphocytes.
    Lancet. 1984 Dec 15;2(8416):1367-9 PMID: 6150368
  10. HTLV-III infection in brains of children and adults with AIDS encephalopathy.
    Science. 1985 Jan 11;227(4683):177-82 PMID: 2981429
  11. Antimoniotungstate (HPA 23) treatment of three patients with AIDS and one with prodrome.
    Lancet. 1985 Feb 23;1(8426):450-1 PMID: 2857819
  12. Recombinant human interferon alfa-A suppresses HTLV-III replication in vitro.
    Lancet. 1985 Mar 16;1(8429):602-4 PMID: 2857946
  13. Transfusion-associated acquired immunodeficiency syndrome. Evidence for persistent infection in blood donors.
    N Engl J Med. 1985 May 16;312(20):1293-6 PMID: 2985992
  14. Inhibition of human T-cell lymphotropic virus type III in vitro by phosphonoformate.
    Lancet. 1985 Jun 29;1(8444):1480-2 PMID: 2409414
  15. Pharmacological inhibition of infectivity of HTLV-III in vitro.
    Cancer Res. 1985 Sep;45(9 Suppl):4583s-4587s PMID: 2990689
  16. 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):4813-7 PMID: 2991896
  17. 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):5199-202 PMID: 2991911
  18. Synthesis and biological activity of several amino analogues of thymidine.
    J Med Chem. 1978 Jan;21(1):109-12 PMID: 563460
  19. Suramin: a potent inhibitor of the reverse transcriptase of RNA tumor viruses.
    Cancer Lett. 1979 Nov;8(1):9-22 PMID: 92362
  20. 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):311-5 PMID: 6263975
  21. 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):1425-31 PMID: 6272109
  22. An outbreak of community-acquired Pneumocystis carinii pneumonia: initial manifestation of cellular immune dysfunction.
    N Engl J Med. 1981 Dec 10;305(24):1431-8 PMID: 6975437
  23. Severe acquired immunodeficiency in male homosexuals, manifested by chronic perianal ulcerative herpes simplex lesions.
    N Engl J Med. 1981 Dec 10;305(24):1439-44 PMID: 6272110
  24. Limiting dilution analysis of Epstein-Barr virus-induced immunoglobulin production by human B cells.
    J Exp Med. 1983 Jan 1;157(1):1-14 PMID: 6294212
  25. Isolation and transmission of human retrovirus (human t-cell leukemia virus).
    Science. 1983 Feb 18;219(4586):856-9 PMID: 6600519
  26. Isolation of a T-lymphotropic retrovirus from a patient at risk for acquired immune deficiency syndrome (AIDS).
    Science. 1983 May 20;220(4599):868-71 PMID: 6189183
  27. Epidemic acquired immune deficiency syndrome: epidemiologic evidence for a transmissible agent.
    J Natl Cancer Inst. 1983 Jul;71(1):1-4 PMID: 6575197
  28. Serological analysis of a subgroup of human T-lymphotropic retroviruses (HTLV-III) associated with AIDS.
    Science. 1984 May 4;224(4648):503-5 PMID: 6200937
Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
Published
1985-10-00
Pages
7096-100
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC391317
Subset
IM
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: product@genelibs.com