Induction of dormant HIV-1 by sodium butyrate: involvement of the TATA box in the activation of the HIV-1 promoter.
Reactivation of latent HIV-1 is believed to play a major role in the pathogenesis of AIDS. Here we show that sodium butyrate (NaB), which can cause gene induction or cell differentiation, reactivates dormant HIV-1 in vitro in chronically infected cells of T-lymphoid and monocytoid origin. The effect of NaB on HIV-1 expression in T-lymphoid cells was apparent 3 h after addition of drug and peaked at 24 h. During this time the proportion of HIV-1 antigen expressing cells increased from less than 0.5 to greater than 90%, and virus production increased by three orders of magnitude. The virus released by the NaB-induced cells was infectious. The extent and kinetics of NaB effects were similar to effects of phorbol 12-myristate 13-acetate in T cells, but not monocytes. Transient expression assays using an indicator gene under the control of the HIV-1 long terminal repeat revealed that mutations which altered the nucleotide sequence in the TATA box significantly reduced the NaB effect. These data show that NaB is a potent inducer of dormant HIV-1 and suggest that the TATA motif is required for this activity.
Golub
E I
EI
Molecular Virology Laboratory, St. Luke's/Roosevelt Hospital Center, New York, NY.
Li
G R
GR
Volsky
D J
DJ
D002087:Butyrates / Q000494:pharmacology*; D020148:Butyric Acid; D002461:Cell Line, Transformed; D004252:DNA Mutational Analysis; D016322:HIV Enhancer / Q000187:drug effects; D016325:HIV Long Terminal Repeat / Q000187:drug effects*; D015497:HIV-1 / Q000187:drug effects*; D007700:Kinetics; D009000:Monocytes / Q000382:microbiology; D013601:T-Lymphocytes / Q000382:microbiology; D016385:TATA Box / Q000187:drug effects*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014775:Virus Activation / Q000187:drug effects*
D002087:Butyrates; D020148:Butyric Acid; D013755:Tetradecanoylphorbol Acetate