The human immunodeficiency virus type 1 Tat antagonist, Ro 5-3335, predominantly inhibits transcription initiation from the viral promoter.
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.
Cupelli
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Roche Research Center, Hoffmann-La Roche, Inc., Nutley, New Jersey 07110.
Hsu
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D000998:Antiviral Agents / Q000494:pharmacology*; D001570:Benzodiazepinones / Q000494:pharmacology*; D015500:Chloramphenicol O-Acetyltransferase / Q000235:genetics; D015696:Gene Products, tat / Q000037:antagonists & inhibitors*; D016325:HIV Long Terminal Repeat; D015497:HIV-1 / Q000235:genetics* / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D011401:Promoter Regions, Genetic; D011758:Pyrroles / Q000494:pharmacology*; D014158:Transcription, Genetic / Q000187:drug effects*; D054322:tat Gene Products, Human Immunodeficiency Virus
D000998:Antiviral Agents; D001570:Benzodiazepinones; D015696:Gene Products, tat; D011758:Pyrroles; D054322:tat Gene Products, Human Immunodeficiency Virus; C072173:Ro 5-3335; D015500:Chloramphenicol O-Acetyltransferase