Suppression of HIV-1 replication by microRNA effectors

doi:10.1186/1742-4690-6-26

Retrovirology

Volume 6

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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

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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
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Suppression of HIV-1 replication by microRNA effectors

Christine Chable-Bessia¹^* , Oussama Meziane¹^* , Daniel Latreille¹^* , Robinson Triboulet¹ , Alessia Zamborlini² , Alexandre Wagschal¹ , Jean-Marc Jacquet³ , Jacques Reynes³ , Yves Levy⁴ , Ali Saib² , Yamina Bennasser¹ and Monsef Benkirane¹

¹Institut de Génétique Humaine CNRS UPR1142, Laboratoire de Virologie Moléculaire, Montpellier, France

²CNRS UMR7151 et Conservatoire National des Arts et Métiers, Paris, France

³Service des Maladies Infectieuses et Tropicales, Centre hospitalier universitaire Montpellier, France

⁴INSERM, Unite U841, Université Paris 12, Faculté de Médecine, AP-HP, Groupe Henri-Mondor Albert-Chenevier, Immunologie clinique, Créteil, F-94010, France

author email corresponding author email* Contributed equally

Retrovirology 2009, 6:26doi:10.1186/1742-4690-6-26


Published:	9 March 2009

Abstract

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.