BRCA1-RAD51 homologous DNA repair pathway promotes HIV-1 reverse transcription.

Abstract

HIV-1 infection triggers multiple cellular pathways that modulate viral replication and may promote latency. Central to this process is the reverse transcription of the viral RNA into DNA and its integration into host chromatin, both processes being regulated by the cell. Emerging evidence suggests that homologous recombination (HR) proteins, especially RAD51, may influence both pre- and post-integration stages. In this study, we show that HIV-1 induces the rapid formation of RAD51 nuclear foci in a BRCA1/2-dependent manner, with RAD51 loading onto viral DNA immediately during reverse transcription. Using ChIP, imaging, and biochemical assays, we demonstrate that this process enhances viral infectivity and reverse transcription efficiency. Our findings reveal a previously unidentified cellular response that recruits repair factors to viral DNA, regulating reverse transcription and influencing viral DNA fate. This work uncovers a previously unknown role for RAD51 in modulating early HIV-1 replication, providing insights into host-virus interactions and potential therapeutic strategies.