Mobility of retroviral genomes triggers cellular responses that participate in the establishment of stable integration of the virus into the Host chromatin. Viral genome insertion requires the delivery of the integration complex (intasome) to the chromosomal insertion locus followed by the catalysis of integration and post-integrative events. These events include the integration complex disassembly, DNA repair of the insertion site and viral gene transcription. We have previously shown that the DNA homologous repair (HR) processes can modulate both the HIV-1 pre-integrative and post-integrative stages (1–3).

We report here that nuclear foci of the HR RAD51 recombinase are triggered during the early phases of the retroviral infection by a mechanism dependent on the BRCA1/BRCA2 repair pathway. CHiP and imaging approaches indicate that RAD51 is loaded onto the incoming viral DNA as soon as it is synthesized during reverse transcription and before integration into chromatin. Inhibition of this process leads to a decrease in viral infectivity and integration associated with inhibition of reverse transcription and increased persistence of unintegrated viral DNA forms.

Our results thus reveal a new mechanism of cellular response to incoming retroviral genomes participating in regulating the early reverse transcription process, the fate of the different populations of viral DNA and possibly the establishment of persistent and/or latent HIV-1 virus reservoirs.

1. Cosnefroy,O et al., J Virol,2012

2. Thierry,S. et al., Chem Biol 2015

3. Matysiak,J., et al., Retrovirology 2017

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