Research
Suppression of HIV-1 replication by microRNA effectors
-
* Corresponding authors: Yamina Bennasser yamina.bennasser@igh.cnrs.fr - Monsef Benkirane monsef.benkirane@igh.cnrs.fr
- † Equal contributors
1 Institut de Génétique Humaine CNRS UPR1142, Laboratoire de Virologie Moléculaire, Montpellier, France
2 CNRS UMR7151 et Conservatoire National des Arts et Métiers, Paris, France
3 Service des Maladies Infectieuses et Tropicales, Centre hospitalier universitaire Montpellier, France
4 INSERM, Unite U841, Université Paris 12, Faculté de Médecine, AP-HP, Groupe Henri-Mondor Albert-Chenevier, Immunologie clinique, Créteil, F-94010, France
Retrovirology 2009, 6:26 doi:10.1186/1742-4690-6-26
Published: 9 March 2009Abstract
The rate of HIV-1 gene expression is a key step that determines the kinetics of virus spread and AIDS progression. Viral entry and gene expression were described to be the key determinants for cell permissiveness to HIV. Recent reports highlighted the involvement of miRNA in regulating HIV-1 replication post-transcriptionally. In this study we explored the role of cellular factors required for miRNA-mediated mRNA translational inhibition in regulating HIV-1 gene expression. Here we show that HIV-1 mRNAs associate and co-localize with components of the RNA Induced Silencing Complex (RISC), and we characterize some of the proteins required for miRNA-mediated silencing (miRNA effectors). RCK/p54, GW182, LSm-1 and XRN1 negatively regulate HIV-1 gene expression by preventing viral mRNA association with polysomes. Interestingly, knockdown of RCK/p54 or DGCR8 resulted in virus reactivation in PBMCs isolated from HIV infected patients treated with suppressive HAART.