The human immunodeficiency virus type 1 Tat antagonist, Ro 5-3335, predominantly inhibits transcription initiation from the viral promoter

J Virol. 1995 Apr;69(4):2640-3. doi: 10.1128/JVI.69.4.2640-2643.1995.

Abstract

Tat, the transcriptional transactivator protein of the human immunodeficiency virus type 1 (HIV-1), is required for viral replication in vitro. The Tat antagonist, Ro 5-3335, and its analog, Ro 24-7429, have been shown to inhibit replication of HIV-1 and to reduce steady-state viral RNA in infected cells (M.-C. Hsu et al., Science 254:1799-1802, 1991, and M.-C. Hsu et al., Proc. Natl. Acad. Sci. USA 90:6395-6399, 1993). Analysis of HIV-1 long terminal repeat-driven reporter gene transcription in a recombinant adenovirus by nuclear run-on assay indicated that the drug predominantly inhibits Tat-dependent initiation and also exerts a measurable effect on elongation. This result may imply a common mechanism for Tat-mediated transcription initiation and elongation.

MeSH terms

  • Antiviral Agents / pharmacology*
  • Benzodiazepinones / pharmacology*
  • Chloramphenicol O-Acetyltransferase / genetics
  • Gene Products, tat / antagonists & inhibitors*
  • HIV Long Terminal Repeat
  • HIV-1 / genetics*
  • HIV-1 / metabolism
  • HeLa Cells
  • Humans
  • Promoter Regions, Genetic*
  • Pyrroles / pharmacology*
  • Transcription, Genetic / drug effects*
  • tat Gene Products, Human Immunodeficiency Virus

Substances

  • Antiviral Agents
  • Benzodiazepinones
  • Gene Products, tat
  • Pyrroles
  • tat Gene Products, Human Immunodeficiency Virus
  • Ro 5-3335
  • Chloramphenicol O-Acetyltransferase