A Tat antagonist inhibits HIV-1 induction in naturally infected and experimentally infected T cells.
Ro 5-3335, a novel antagonist of human immunodeficiency virus type 1 (HIV-1) Tat activity, inhibits acute and chronic HIV-1 infection in T lymphocytes. Here we describe the effects of Ro 5-3335 on the accumulation of viral DNA during primary infection, the induction of virus from a latently infected cell line, and the expression of virus upon activation of naturally infected T cells. Ro 5-3335 permitted initial DNA synthesis during primary infection, but inhibited the subsequent increase in viral DNA copy number. The induction of HIV-1, as determined by the synthesis of p24 core antigen, was inhibited by 99% by Ro 5-3335 in both the model cell line and naturally infected T cells.
Potash
M J
MJ
Molecular Virology Laboratory, St. Lukes/Roosevelt Hospital Center, Columbia University, New York, New York.
Bentsman
G
G
McKinley
G
G
Volsky
D J
DJ
D000163:Acquired Immunodeficiency Syndrome / Q000276:immunology / Q000382:microbiology*; D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology*; D001570:Benzodiazepinones / Q000494:pharmacology*; D002460:Cell Line; D003001:Cloning, Molecular; D004279:DNA, Viral / Q000096:biosynthesis* / Q000235:genetics / Q000302:isolation & purification; D015696:Gene Products, tat / Q000037:antagonists & inhibitors*; D016655:HIV Core Protein p24 / Q000032:analysis / Q000096:biosynthesis; D015497:HIV-1 / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D011758:Pyrroles / Q000494:pharmacology*; D051381:Rats; D013601:T-Lymphocytes / Q000382:microbiology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D054322:tat Gene Products, Human Immunodeficiency Virus
D000998:Antiviral Agents; D001570:Benzodiazepinones; D004279:DNA, Viral; D015696:Gene Products, tat; D016655:HIV Core Protein p24; D011758:Pyrroles; D054322:tat Gene Products, Human Immunodeficiency Virus; C072173:Ro 5-3335; D013755:Tetradecanoylphorbol Acetate