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. Design: The effect of RA and nuclear factor (NF)-kappa B on HIV-1 promoter activit y was investigated using HIV-1 long terminal repeat (LTR)-based report er constructs. Methods: The activity of wild type and mutant LTR seque nces was compared in a variety of stably and transiently transfected h uman cell lines. Results: It was shown that RA treatment inhibits both the basal activity of the HIV-1 LTR and its stimulation by phorbol es ter treatment. This inhibition is observed in both HeLa cells (in the presence of exogenously supplied RA receptors) and the naturally RA-re sponsive U937 monocyte cell line. RA can also inhibit the stimulation of the HIV-1 LTR by overexpression of NF-KB subunits, while linkage of the NF-KB sites in the HIV promoter to a heterologous promoter result s in its inhibition by RA. Conclusions: The data presented clearly dem onstrate a negative effect of RA on HIV-1 LTR activity that may contri bute to its effect on viral replication.