Restoration of cell surface CD4 expression in human immunodeficiency virus type 1-infected cells by treatment with a Tat antagonist.
Productive infection of T lymphocytes with human immunodeficiency virus type 1 (HIV-1) is accompanied by a diminution of surface CD4 receptors. Treatment of chronically HIV-1-infected CD4-negative T cells in vitro with the Tat antagonist Ro 5-3335 resulted in a drug dose-dependent decrease in virus protein production and a reciprocal increase in surface CD4 display. The drug-treated cells remained viable, showed significantly reduced levels of the full-length and spliced HIV-1 mRNAs as detected by Northern (RNA) blot hybridization, and maintained integrated HIV-1 DNA. In immunoprecipitation studies with drug-treated cells, the levels of free 55-kDa CD4 protein increased and gp160 complexed with CD4 decreased in amount. These results show for the first time that certain cytopathogenic effects of chronic HIV-1 infection can be reversed by suppressing virus expression.
Shahabuddin
M
M
Molecular Virology Laboratory, St. Luke's/Roosevelt Hospital Center, New York, New York.
Volsky
B
B
Hsu
M C
MC
Volsky
D J
DJ
D000998:Antiviral Agents / Q000494:pharmacology; D001570:Benzodiazepinones / Q000494:pharmacology*; D015704:CD4 Antigens / Q000096:biosynthesis* / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D015686:Gene Products, env / Q000096:biosynthesis; D015696:Gene Products, tat / Q000378:metabolism*; D019302:HIV Envelope Protein gp160; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D011498:Protein Precursors / Q000096:biosynthesis; D011758:Pyrroles / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D013601:T-Lymphocytes / Q000187:drug effects / Q000378:metabolism; D014779:Virus Replication / Q000187:drug effects; D054322:tat Gene Products, Human Immunodeficiency Virus
D000998:Antiviral Agents; D001570:Benzodiazepinones; D015704:CD4 Antigens; D015686:Gene Products, env; D015696:Gene Products, tat; D019302:HIV Envelope Protein gp160; D011498:Protein Precursors; D011758:Pyrroles; D012333:RNA, Messenger; D054322:tat Gene Products, Human Immunodeficiency Virus; C072173:Ro 5-3335