003 UVB dose and cell cycle conditions influence the outcome of UVB‐induced HIV activation

Having reported previously that suberythmogenic doses of UVB activate HIV in human skin as shown by a 6–10 fold rise in HIV-1 gag, gene by RT-PCR and similar increments in HIV+ lymphocytes and dendritic cells by RT-PCR-ISH, we dissected the mechanisms underlying these events. Thus, we examined effects of UVB (0–200 J/m2) on HIV transcription, cell cycle distribution, and apoptosis on two Jurkat cell lines (1G5 and DC10). 1G5 and DC10 lines are identical in bearing the HIV-LTR-driven luciferase (Luc) gene, but with the latter also carrying the tat gene. Whereas lower doses of UVB (up to 50 J/m2 induced Luc expression in a UVB dose-dependent manner in DC10 cells and G2/M arrest of these cells, it produced only minimal Luc expression in 1G5 cells with no cell cycle arrest noted. By contrast. higher doses of UVB (100–200 J/m2) led to reduced Luc expression and to apoptosis in DC10 cells, but not in 1G5 cells. Our results are consistent with the concept that activation of the HIV promoter by UVB is dependent on tat. The G2/M arrest induced by lower-dose UVB may allow accumulation of HIV in activated lvmphoeytes; DNA repair may complete the cell cycle leading to proliferation of HIV+ cells. Apoptosis induced by higher-dose UVB reduced HIV transcription, but may also release viral particles from dying cells. These findings indicate that even small increments within a subelythmogenic UVB dose range can have a dramatic impact on HIV transcription, that in turn may be related to altered cell cycle programs. Thus, the precise UVB dose and other inter-current skin conditions affecting cell cycles (e.g., medications, diseases and infections other than HIV) at the time of UVB exposure may influence the net outcome of HIV activation in skin.