Suppression of HIV-1 replication by microRNA effectors

被引:93
作者
Chable-Bessia, Christine [1 ]
Meziane, Oussama [1 ]
Latreille, Daniel [1 ]
Triboulet, Robinson [1 ]
Zamborlini, Alessia [2 ]
Wagschal, Alexandre [1 ]
Jacquet, Jean-Marc [3 ]
Reynes, Jacques
Levy, Yves [4 ]
Saib, Ali [2 ]
Bennasser, Yamina [1 ]
Benkirane, Monsef [1 ]
机构
[1] Inst Genet Humaine CNRS, Mol Virol Lab, UPR1142, Montpellier, France
[2] CNRS, UMR7151, Paris, France
[3] Ctr Hosp Univ Montpellier, Serv Malad Infect & Trop, F-34059 Montpellier, France
[4] Univ Paris 12, INSERM, AP HP, Unite U841,Fac Med,Grp Henri Mondor Albert Chenev, F-94010 Creteil, France
来源
RETROVIROLOGY | 2009年 / 6卷
关键词
MEDIATED TRANSLATIONAL REPRESSION; SMALL INTERFERING RNAS; CD4(+) T-LYMPHOCYTES; SMALL NONCODING RNAS; GENE-EXPRESSION; MESSENGER-RNA; RIBONUCLEOPROTEIN COMPLEXES; CELLULAR MICRORNAS; STRESS GRANULES; HUMAN-CELLS;
D O I
10.1186/1742-4690-6-26
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
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.
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页数:11
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