Dual and Opposite Effects of hRAD51 Chemical Modulation on HIV-1 Integration

Sylvain Thierry, Mohamed Salah Benleulmi, Ludivine Sinzelle, Eloise Thierry, Christina Calmels, Stephane Chaignepain, Pierre Waffo-Teguo, Jean Michel Merillon, Brian Budke, Jean Max Pasquet, Simon Litvak, Angela Ciuffi, Patrick Sung, Philip Connell, Ilona Hauber, Joachim Hauber, Marie Line Andreola, Olivier Delelis, Vincent Parissi

Research output: Contribution to journalArticle

3 Scopus citations

Abstract

Summary 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.

Original languageEnglish (US)
Pages (from-to)712-723
Number of pages12
JournalChemistry and Biology
Volume22
Issue number6
DOIs
StatePublished - Jun 18 2015
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmacology
  • Drug Discovery
  • Clinical Biochemistry

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    Thierry, S., Benleulmi, M. S., Sinzelle, L., Thierry, E., Calmels, C., Chaignepain, S., Waffo-Teguo, P., Merillon, J. M., Budke, B., Pasquet, J. M., Litvak, S., Ciuffi, A., Sung, P., Connell, P., Hauber, I., Hauber, J., Andreola, M. L., Delelis, O., & Parissi, V. (2015). Dual and Opposite Effects of hRAD51 Chemical Modulation on HIV-1 Integration. Chemistry and Biology, 22(6), 712-723. https://doi.org/10.1016/j.chembiol.2015.04.020