Retinoic acid inhibits both the basal activity and phorbol ester-mediated activation of the HIV long terminal repeat promoter.
OBJECTIVE
To establish whether the steroid hormone retinoic acid (RA) was able to modulate the activity of the HIV-1 promoter.


METHODS
The effect of RA and nuclear factor (NF)-kappa B on HIV-1 promoter activity was investigated using HIV-1 long terminal repeat (LTR)-based reporter constructs.


METHODS
The activity of wild type and mutant LTR sequences was compared in a variety of stably and transiently transfected human cell lines.


RESULTS
It was shown that RA treatment inhibits both the basal activity of the HIV-1 LTR and its stimulation by phorbol ester treatment. This inhibition is observed in both HeLa cells (in the presence of exogenously supplied RA receptors) and the naturally RA-responsive U937 monocyte cell line. RA can also inhibit the stimulation of the HIV-1 LTR by overexpression of NF-kappa B subunits, while linkage of the NF-kappa B sites in the HIV promoter to a heterologous promoter results in its inhibition by RA.


CONCLUSIONS
The data presented clearly demonstrate a negative effect of RA on HIV-1 LTR activity that may contribute to its effect on viral replication.
Towers
G
G
Chester Beatty Laboratories, Institute of Cancer Research, London, UK.
Harris
J
J
Lang
G
G
Collins
M K
MK
Latchman
D S
DS
D001483:Base Sequence; D005786:Gene Expression Regulation; D018014:Gene Transfer Techniques; D016325:HIV Long Terminal Repeat / Q000235:genetics*; D006367:HeLa Cells; D006801:Humans; D008969:Molecular Sequence Data; D009000:Monocytes / Q000378:metabolism / Q000821:virology; D010957:Plasmids; D011401:Promoter Regions, Genetic; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D014158:Transcription, Genetic; D014212:Tretinoin / Q000494:pharmacology*
D014212:Tretinoin; D013755:Tetradecanoylphorbol Acetate