title: Integrase mutants defective for interaction with LEDGF/p75 are impaired in chromosome tethering and HIV-1 replication.
abstract: The insertion of a DNA copy of its RNA genome into a chromosome of the host cell is mediated by the viral integrase with the help of mostly uncharacterized cellular cofactors. We have recently described that the transcriptional co-activator LEDGF/p75 strongly interacts with HIV-1 integrase. Here we show that interaction of HIV-1 integrase with LEDGF/p75 is important for viral replication. Using multiple approaches including two-hybrid interaction studies, random and directed mutagenesis, we could demonstrate that HIV-1 virus harboring a single mutation that disrupts integrase-LEDGF/p75 interaction, resulted in defective HIV-1 replication. Furthermore, we found that LEDGF/p75 tethers HIV-1 integrase to chromosomes and that this interaction may be important for the integration process and the replication of HIV-1.
authors.affiliation: Institut Cochin, U567 INSERM, UPR8104 CNRS, Université Paris VI et VII, Tour 43, 2e étage, couloir 43-44, 2 place Jussieu, F-75251 Paris cedex 05, France.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Emiliani
authors.forename: Aurélie
authors.initials: A
authors.lastname: Mousnier
authors.forename: Katrien
authors.initials: K
authors.lastname: Busschots
authors.forename: Marlène
authors.initials: M
authors.lastname: Maroun
authors.forename: Bénédicte
authors.initials: B
authors.lastname: Van Maele
authors.forename: Denis
authors.initials: D
authors.lastname: Tempé
authors.forename: Linos
authors.initials: L
authors.lastname: Vandekerckhove
authors.forename: Fanny
authors.initials: F
authors.lastname: Moisant
authors.forename: Lilia
authors.initials: L
authors.lastname: Ben-Slama
authors.forename: Myriam
authors.initials: M
authors.lastname: Witvrouw
authors.forename: Frauke
authors.initials: F
authors.lastname: Christ
authors.forename: Jean-Christophe
authors.initials: JC
authors.lastname: Rain
authors.forename: Catherine
authors.initials: C
authors.lastname: Dargemont
authors.forename: Zeger
authors.initials: Z
authors.lastname: Debyser
authors.forename: Richard
authors.initials: R
authors.lastname: Benarous
mesh_terms: D002877:Chromosomes, Human / Q000821:virology; D005973:Glutamine / Q000378:metabolism; D015658:HIV Infections / Q000235:genetics / Q000378:metabolism / Q000821:virology*; D019427:HIV Integrase / Q000235:genetics* / Q000378:metabolism*; D015497:HIV-1 / Q000235:genetics / Q000254:growth & development*; D006367:HeLa Cells; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism*; D016662:Virus Integration / Q000502:physiology; D014779:Virus Replication / Q000502:physiology
chemical_list: D036341:Intercellular Signaling Peptides and Proteins; C119380:lens epithelium-derived growth factor; D005973:Glutamine; D019427:HIV Integrase