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

Proc Natl Acad Sci U S A. 1985 Oct;82(20):7096-100. doi: 10.1073/pnas.82.20.7096.

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*
  • Deltaretrovirus / genetics
  • Deltaretrovirus / pathogenicity
  • Gene Products, gag
  • Humans
  • RNA-Directed DNA Polymerase / metabolism
  • Retroviridae Proteins / genetics
  • Thymidine / analogs & derivatives*
  • Thymidine / pharmacology
  • Transcription, Genetic / drug effects
  • Zidovudine

Substances

  • Antiviral Agents
  • Gene Products, gag
  • Retroviridae Proteins
  • Zidovudine
  • RNA-Directed DNA Polymerase
  • Thymidine