TY - JOUR
T1 - Dual and Opposite Effects of hRAD51 Chemical Modulation on HIV-1 Integration
AU - Thierry, Sylvain
AU - Benleulmi, Mohamed Salah
AU - Sinzelle, Ludivine
AU - Thierry, Eloise
AU - Calmels, Christina
AU - Chaignepain, Stephane
AU - Waffo-Teguo, Pierre
AU - Merillon, Jean Michel
AU - Budke, Brian
AU - Pasquet, Jean Max
AU - Litvak, Simon
AU - Ciuffi, Angela
AU - Sung, Patrick
AU - Connell, Philip
AU - Hauber, Ilona
AU - Hauber, Joachim
AU - Andreola, Marie Line
AU - Delelis, Olivier
AU - Parissi, Vincent
N1 - Publisher Copyright:
© 2015 Elsevier Ltd. All rights reserved.
PY - 2015/6/18
Y1 - 2015/6/18
N2 - 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.
AB - 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.
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U2 - 10.1016/j.chembiol.2015.04.020
DO - 10.1016/j.chembiol.2015.04.020
M3 - Article
C2 - 26051216
AN - SCOPUS:84931573115
VL - 22
SP - 712
EP - 723
JO - Cell Chemical Biology
JF - Cell Chemical Biology
SN - 2451-9448
IS - 6
ER -