Effect of retinoic acid on the replication of human immunodeficiency virus in HTLV-I-positive MT-4 cells.

The inhibitory effect of all-trans-retinoic acid (RA) on human immunodeficiency virus (HIV) replication upon infection was studied quantitatively using a novel bioassay system with a HTLV-I-carrying human T-cell line, MT-4. The results can be summarized as follows. The appearance of HIV antigen was significantly reduced when the cells were treated with more than 1 microgram/ml of the chemical after infection. When HIV specific plaque assay was performed to titrate the virus from the supernatant of culture treated with 10 micrograms/ml of RA no plaques were observed. When RA was applied directly in the plaque assay, significant decrease of the number of plaques was discerned showing 68, 66, 47 and 16, at doses of 0.1, 1, 5, and 10 micrograms/ml of RA, while 102 plaques were formed in the control dish. The appearance of cytopathic effects of MT-4 cells by HIV was more delayed in RA-treated cultures than in untreated cultures. Concomitant treatment of the cells with 5 micrograms/ml of RA and various concentrations of suramin resulted in the more effective inhibition of HIV replication than suramin alone. RA did not inhibit the reverse transcriptase activity (RT) of HIV directly. These data suggest that RA inhibits HIV replication by inducing an antiviral state in the cells.