| Literature DB >> 26051216 |
Sylvain Thierry1, Mohamed Salah Benleulmi2, Ludivine Sinzelle2, Eloise Thierry1, Christina Calmels2, Stephane Chaignepain3, Pierre Waffo-Teguo4, Jean-Michel Merillon4, Brian Budke5, Jean-Max Pasquet6, Simon Litvak2, Angela Ciuffi7, Patrick Sung8, Philip Connell5, Ilona Hauber9, Joachim Hauber9, Marie-Line Andreola2, Olivier Delelis1, Vincent Parissi10.
Abstract
The cellular DNA repair hRAD51 protein has been shown to restrict HIV-1 integration both in vitro and in vivo. To investigate its regulatory functions, we performed a pharmacological analysis of the retroviral integration modulation by hRAD51. We found that, in vitro, chemical activation of hRAD51 stimulates its integration inhibitory properties, whereas inhibition of hRAD51 decreases the integration restriction, indicating that the modulation of HIV-1 integration depends on the hRAD51 recombinase activity. Cellular analyses demonstrated that cells exhibiting high hRAD51 levels prior to de novo infection are more resistant to integration. On the other hand, when hRAD51 was activated during integration, cells were more permissive. Altogether, these data establish the functional link between hRAD51 activity and HIV-1 integration. Our results highlight the multiple and opposite effects of the recombinase during integration and provide new insights into the cellular regulation of HIV-1 replication.Entities:
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Year: 2015 PMID： 26051216 PMCID： PMC4889029 DOI： 10.1016/j.chembiol.2015.04.020
Source DB: PubMed Journal: Chem Biol ISSN： 1074-5521