Retroviral integration site selection: a running Gag?

The ability of retroviruses to integrate their genomes into host chromatin is a key step for the completion of their replication cycle. Selection of a suitable chromosomal integration site has been described as a hierarchical mechanism involving both cellular and viral proteins but the exact molecular determinants are still unclear. We recently showed that the spumaretrovirus prototype foamy virus (PFV) Gag protein is acting as a chromatin tether by interacting with the nucleosome acidic patch (Lesbats et al. PNAS 114(21)). Disruption of the nucleosome binding leads to a dramatic delocalization of both the viral particles and the integration sites accompanied with a reduction of integrated genes expression. These data show for the first time a direct interaction between retroviral structural proteins with the host chromosomes, and highlight their importance in the integration sites selection.