Suppression of HIV-1 replication by microRNA effectors

Archive ouverte

Chable-Bessia, C. | Meziane, O. | Latreille, D. | Triboulet, R. | Zamborlini, A. | Wagschal, A. | Jacquet, Jm | Reynes, J. | Levy, Y. | Saib, A. | Bennasser, Y. | Benkirane, M.

Edité par CCSD ; BioMed Central -

International audience. The rate of HIV-1 gene expression is a key step that determines the kinetics of virus spread andAIDS progression. Viral entry and gene expression were described to be the key determinants forcell permissiveness to HIV. Recent reports highlighted the involvement of miRNA in regulatingHIV-1 replication post-transcriptionally. In this study we explored the role of cellular factorsrequired 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 InducedSilencing Complex (RISC), and we characterize some of the proteins required for miRNA-mediatedsilencing (miRNA effectors). RCK/p54, GW182, LSm-1 and XRN1 negatively regulate HIV-1 geneexpression by preventing viral mRNA association with polysomes. Interestingly, knockdown ofRCK/p54 or DGCR8 resulted in virus reactivation in PBMCs isolated from HIV infected patientstreated with suppressive HAART.

• Description
• Sujet/Public
• Outil
• Outil d'anticipation
• Mémoire et thèse
• Gestion