Suppression of HIV-1 replication by microRNA effectors.
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.
Chable-Bessia
Christine
C
Institut de Génétique Humaine CNRS UPR1142, Laboratoire de Virologie Moléculaire, Montpellier, France. christine.chable-bessia@igh.cnrs.fr
Meziane
Oussama
O
Latreille
Daniel
D
Triboulet
Robinson
R
Zamborlini
Alessia
A
Wagschal
Alexandre
A
Jacquet
Jean-Marc
JM
Reynes
Jacques
J
Levy
Yves
Y
Saib
Ali
A
Bennasser
Yamina
Y
Benkirane
Monsef
M
D060565:Argonaute Proteins; D002460:Cell Line; D002478:Cells, Cultured; D053487:DEAD-box RNA Helicases / Q000235:genetics / Q000378:metabolism; D015852:Eukaryotic Initiation Factor-2 / Q000378:metabolism; D015967:Gene Expression Regulation, Viral; D055785:Gene Knockdown Techniques; D015497:HIV-1 / Q000502:physiology*; D006367:HeLa Cells; D006801:Humans; D035683:MicroRNAs / Q000378:metabolism*; D011132:Polyribosomes / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D034622:RNA Interference / Q000502:physiology; D012367:RNA, Viral / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D017735:Virus Latency / Q000502:physiology; D014779:Virus Replication / Q000502:physiology*
C466422:AGO2 protein, human; D060565:Argonaute Proteins; D015852:Eukaryotic Initiation Factor-2; C464824:LSM1 protein, human; D035683:MicroRNAs; D011518:Proto-Oncogene Proteins; D012367:RNA, Viral; D016601:RNA-Binding Proteins; C094683:DDX6 protein, human; D053487:DEAD-box RNA Helicases