title: The integrase cofactor LEDGF/p75 associates with Iws1 and Spt6 for postintegration silencing of HIV-1 gene expression in latently infected cells.
abstract: The persistence of a latent reservoir containing transcriptionally silent, but replication-competent, integrated provirus is a serious challenge to HIV eradication. HIV integration is under the control of LEDGF/p75, the cellular cofactor of viral integrase. Investigating possible postintegration roles for LEDGF/p75, we find that LEDGF/p75 represses HIV expression in latently infected cells. LEDGF/p75 associated with two proteins involved in the control of gene expression and chromatin structure, Spt6 and Iws1, to form a stable complex. Iws1 plays a role in the establishment of latent infection, whereas Spt6 functions to recruit Iws1 and LEDGF/p75 to the silenced provirus and maintains histone occupancy at the HIV promoter. In latently infected cells, depletion of the complex results in reactivation of HIV expression Altogether, our results indicate that a complex containing LEDGF/p75, Iws1, and Spt6 participates in regulating postintegration steps of HIV latency.
authors.affiliation: Inserm, U1016, Institut Cochin, 75014 Paris, France; CNRS, UMR8104, 75014 Paris, France; Université Paris Descartes, 75014 Paris, France. Electronic address: anabel.gerard@gmail.com.
authors.forename: Annabelle
authors.initials: A
authors.lastname: Gérard
authors.affiliation: Inserm, U1016, Institut Cochin, 75014 Paris, France; CNRS, UMR8104, 75014 Paris, France; Université Paris Descartes, 75014 Paris, France.
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Ségéral
authors.affiliation: Inserm, U1016, Institut Cochin, 75014 Paris, France; CNRS, UMR8104, 75014 Paris, France; Université Paris Descartes, 75014 Paris, France.
authors.forename: Monica
authors.initials: M
authors.lastname: Naughtin
authors.affiliation: Inserm, U1016, Institut Cochin, 75014 Paris, France; CNRS, UMR8104, 75014 Paris, France; Université Paris Descartes, 75014 Paris, France.
authors.forename: Ahmed
authors.initials: A
authors.lastname: Abdouni
authors.affiliation: Inserm, U1016, Institut Cochin, 75014 Paris, France; CNRS, UMR8104, 75014 Paris, France; Université Paris Descartes, 75014 Paris, France.
authors.forename: Bénédicte
authors.initials: B
authors.lastname: Charmeteau
authors.affiliation: Inserm, U1016, Institut Cochin, 75014 Paris, France; CNRS, UMR8104, 75014 Paris, France; Université Paris Descartes, 75014 Paris, France.
authors.forename: Rémi
authors.initials: R
authors.lastname: Cheynier
authors.affiliation: Hybrigenics, SA, Paris, 75014 France.
authors.forename: Jean-Christophe
authors.initials: JC
authors.lastname: Rain
authors.affiliation: Inserm, U1016, Institut Cochin, 75014 Paris, France; CNRS, UMR8104, 75014 Paris, France; Université Paris Descartes, 75014 Paris, France. Electronic address: stephane.emiliani@inserm.fr.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Emiliani
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D002460:Cell Line; D015967:Gene Expression Regulation, Viral; D015497:HIV-1 / Q000502:physiology*; D054884:Host-Pathogen Interactions; D006801:Humans; D011506:Proteins / Q000378:metabolism*; D011533:Proviruses / Q000502:physiology; D016601:RNA-Binding Proteins; D014157:Transcription Factors / Q000378:metabolism*; D016662:Virus Integration; D017735:Virus Latency
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C510636:Iws1 protein, human; C504649:PSIP1 protein, human; D011506:Proteins; D016601:RNA-Binding Proteins; C100927:SUPT6H protein, human; D014157:Transcription Factors