Dual and Opposite Effects of hRAD51 Chemical Modulation on HIV-1 Integration.
PASQUET, Jean-Max
INSERM U1035, Université de Bordeaux, UFR Sciences de la Vie et de la Santé, 33000 Bordeaux
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INSERM U1035, Université de Bordeaux, UFR Sciences de la Vie et de la Santé, 33000 Bordeaux
Language
EN
Article de revue
This item was published in
Journal of Chemical Biology. 2015-06-18, vol. 22, n° 6, p. 712-23
English 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 ...Read more >
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.Read less <
English Keywords
4
4'-Diisothiocyanostilbene-2
2'-Disulfonic Acid
Aptamers
Nucleotide
Benzamides
DNA
DNA Repair
Gene Expression
HEK293 Cells
HIV-1
Humans
Morpholines
Protein Binding
Pyrroles
Rad51 Recombinase
Stilbenes
Sulfonamides
Virus Internalization
Virus Replication