title: Suppression of HIV-1 replication by microRNA effectors.
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.
authors.affiliation: Institut de Génétique Humaine CNRS UPR1142, Laboratoire de Virologie Moléculaire, Montpellier, France. christine.chable-bessia@igh.cnrs.fr
authors.forename: Christine
authors.initials: C
authors.lastname: Chable-Bessia
authors.forename: Oussama
authors.initials: O
authors.lastname: Meziane
authors.forename: Daniel
authors.initials: D
authors.lastname: Latreille
authors.forename: Robinson
authors.initials: R
authors.lastname: Triboulet
authors.forename: Alessia
authors.initials: A
authors.lastname: Zamborlini
authors.forename: Alexandre
authors.initials: A
authors.lastname: Wagschal
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Jacquet
authors.forename: Jacques
authors.initials: J
authors.lastname: Reynes
authors.forename: Yves
authors.initials: Y
authors.lastname: Levy
authors.forename: Ali
authors.initials: A
authors.lastname: Saib
authors.forename: Yamina
authors.initials: Y
authors.lastname: Bennasser
authors.forename: Monsef
authors.initials: M
authors.lastname: Benkirane
mesh_terms: 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*
chemical_list: 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