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
-
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
-
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
-
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
-
Selective tropism of lymphadenopathy associated virus (LAV) for helper-inducer T lymphocytes.
Science. 1984 Jul 6;225(4657):59-63
PMID: 6328660
-
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
-
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
-
A pathogenic retrovirus (HTLV-III) linked to AIDS.
N Engl J Med. 1984 Nov 15;311(20):1292-7
PMID: 6208484
-
Prevalence of antibodies to lymphadenopathy-associated retrovirus in African patients with AIDS.
Science. 1984 Oct 26;226(4673):453-6
PMID: 6238406
-
Ribavirin suppresses replication of lymphadenopathy-associated virus in cultures of human adult T lymphocytes.
Lancet. 1984 Dec 15;2(8416):1367-9
PMID: 6150368
-
HTLV-III infection in brains of children and adults with AIDS encephalopathy.
Science. 1985 Jan 11;227(4683):177-82
PMID: 2981429
-
Antimoniotungstate (HPA 23) treatment of three patients with AIDS and one with prodrome.
Lancet. 1985 Feb 23;1(8426):450-1
PMID: 2857819
-
Recombinant human interferon alfa-A suppresses HTLV-III replication in vitro.
Lancet. 1985 Mar 16;1(8429):602-4
PMID: 2857946
-
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
-
Inhibition of human T-cell lymphotropic virus type III in vitro by phosphonoformate.
Lancet. 1985 Jun 29;1(8444):1480-2
PMID: 2409414
-
Pharmacological inhibition of infectivity of HTLV-III in vitro.
Cancer Res. 1985 Sep;45(9 Suppl):4583s-4587s
PMID: 2990689
-
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
-
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
-
Synthesis and biological activity of several amino analogues of thymidine.
J Med Chem. 1978 Jan;21(1):109-12
PMID: 563460
-
Suramin: a potent inhibitor of the reverse transcriptase of RNA tumor viruses.
Cancer Lett. 1979 Nov;8(1):9-22
PMID: 92362
-
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
-
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
-
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
-
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
-
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
-
Isolation and transmission of human retrovirus (human t-cell leukemia virus).
Science. 1983 Feb 18;219(4586):856-9
PMID: 6600519
-
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
-
Epidemic acquired immune deficiency syndrome: epidemiologic evidence for a transmissible agent.
J Natl Cancer Inst. 1983 Jul;71(1):1-4
PMID: 6575197
-
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