Activation of HIV-1 LTR by Rad51 in microglial cells

Abstract

Infection with HIV-1 induces a variety of biological alterations to the host that are beneficial to the life cycle of the virus but may have adverse effects on the host cell. Here we demonstrate that expression of Rad51, a major component of the homologous recombination-directed DNA repair (HRR) pathway, is induced upon HIV-1 infection of microglial cells. Activation of Rad51 expression positively impacts on HIV-1 LTR transcription through a region of the viral promoter known for binding the inducible transcription factor NF-κB. Rad51 showed the ability to form a complex with the p65 subunit of NF-κB and regulate the level of p65 interaction with LTR DNA encompassing the κB motif. This study provides evidence for reciprocal interaction of HIV-1 and a host DNA repair protein that impacts on expression of the viral genome. These results also point to the ability of HIV-1 to recruit proteins involved in DNA repair that are necessary for retroviral DNA integration, efficient replication and prevention of viral-induced cell death.