Reactivation Of Latent Hiv-1 Via Aid/Apobec

The eradication of HIV by current anti-retroviral therapies in infected individuals is not accomplished due to the establishment of viral latency during early stages of infection. HIV establishes long-lived latent infection in resting memory T lymphocytes and other non-dividing cells. Multiple mechanisms contribute to the maintenance of HIV latency, including epigenetic silencing.Here we are reporting the HIV-1 latency reactivation in J-Lat cells, throughout AID transfection alone or together Mbd4 and Gadd45α.Our results indicated HIV reactivation levels in J-lat 6.3 and 8.4 (1.6% and 2.5%) with AID transfected alone. Cells co-transfected with AID, Mbd4 and Gadd45α, presented highest levels of HIV-1 latency reactivation. The interaction between AID/APOBEC, Mbd4, and Gadd45α has already been reported in zebrafish. In the proposed mechanism, CpG demethylation iniciates with AID action in promoter regions and consequent gene activation, while Mbd4 is responsible for breakdown of the glycosidic bond and consequent removal of the generated thymine. Gadd45α would be one of the enzymes involved in the base excision repair, besides being responsible for the stabilization of the enzymatic complex formed. According to the data presented here, a similar mechanism could be occurring in HIV-1 latency reactivation. Further experiments are needed to elucidate this reactivation pathway, however, this is the first report of the action of the AID-APOBEC protein on reactivation of latent HIV-1 and the investigation of these data can generate an important step for the HIV cure.