All-Trans Retinoic Acid Can Reduce Proviral DNA of Human T-Cell Leukemia Virus as a Reverse Transcriptase Inhibitor.

We previously reported that all-trans retinoic acid (ATRA) inhibits growth in HTLV-1-positive T-cell lines and fresh cells from patients with adult T-cell leukemia. However, the mechanism of this inhibition is not clear. In the present study, we observed the NF-κB transcriptional activity as well as cell growth in HTLV-1-positive T-cell lines decreased significantly in these cells in the presence of ATRA. However, no significant growth inhibition was observed after treatment with IFN-γ, TNF-α, and TGF-β of growth inhibitory cytokines induced by ATRA. Thereafter, we observed that ATRA reduced HTLV-1 proviral DNA, gag and tax mRNA load using a real time quantitative polymerase chain reaction and soluble IL-2 receptor in the culture supernatant using ELISA in HTLV-1-positive T-cell lines. Interestingly, ATRA significantly inhibited reverse transcriptase activity similar to azidothymidine in HTLV-1-positive T-cell lines. These results suggested that ATRA could inhibit reverse transcriptase activity in the growth inhibition of ATL cells. Additionally, an effect of ATRA on replication of the human immunodeficiency virus (HIV) was also observed. ATRA significantly reduced the HIV proviral DNA load of both a HIV-1-positive cell line and HIV-1-infected patients. These results indicated that ATRA may be useful for HIV treatment in a clinical setting.