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

Details

Ressource 1Download: 26051216 (1).pdf (1898.69 [Ko])
State: Public
Version: Final published version
Serval ID
serval:BIB_20D5436CB5FF
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Dual and Opposite Effects of hRAD51 Chemical Modulation on HIV-1 Integration.
Journal
Chemistry and Biology
Author(s)
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.
ISSN
1879-1301 (Electronic)
ISSN-L
1074-5521
Publication state
Published
Issued date
2015
Peer-reviewed
Oui
Volume
22
Number
6
Pages
712-723
Language
english
Notes
Publication types: Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
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.
Keywords
4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid/chemistry, 4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid/metabolism, Aptamers, Nucleotide/chemistry, Aptamers, Nucleotide/metabolism, Benzamides/chemistry, Benzamides/metabolism, DNA/chemistry, DNA/metabolism, DNA Repair, Gene Expression/drug effects, HEK293 Cells, HIV-1/physiology, Humans, Morpholines/chemistry, Morpholines/metabolism, Protein Binding, Pyrroles/chemistry, Pyrroles/metabolism, Rad51 Recombinase/chemistry, Rad51 Recombinase/genetics, Stilbenes/chemistry, Stilbenes/metabolism, Sulfonamides/chemistry, Sulfonamides/metabolism, Virus Internalization/drug effects, Virus Replication/drug effects
Pubmed
Web of science
Open Access
Yes
Create date
27/08/2015 9:52
Last modification date
20/08/2019 12:57
Usage data