title: Host factors for retroviral integration site selection.
abstract: To achieve productive infection, retroviruses such as HIV stably integrate their reverse transcribed RNA genome into a host chromosome. Each retroviral family preferentially integrates near a unique subset of genomic features. HIV integrase (IN) is targeted to the body of active transcription units through interaction with lens epithelium-derived growth factor (LEDGF/p75). We describe the successful effort to develop inhibitors of the interaction between IN and LEDGF/p75, referred to as LEDGINs. Gammaretroviruses display a distinct integration pattern. Recently, BET (bromo- and extraterminal domain) proteins were identified as the LEDGF/p75 counterparts that target the integration of gammaretroviruses. The identification of the chromatin-readers LEDGF/p75 and BET as cellular cofactors that orchestrate lentiviral or gammaretroviral integration opens new avenues to developing safer viral vectors for gene therapy.
authors.affiliation: Laboratory for Molecular Virology and Gene Therapy, KU Leuven, Leuven 3000, Flanders, Belgium. Electronic address: zeger.debyser@med.kuleuven.be.
authors.forename: Zeger
authors.initials: Z
authors.lastname: Debyser
authors.affiliation: Laboratory for Molecular Virology and Gene Therapy, KU Leuven, Leuven 3000, Flanders, Belgium.
authors.forename: Frauke
authors.initials: F
authors.lastname: Christ
authors.affiliation: Laboratory for Molecular Virology and Gene Therapy, KU Leuven, Leuven 3000, Flanders, Belgium.
authors.forename: Jan
authors.initials: J
authors.lastname: De Rijck
authors.affiliation: Laboratory for Molecular Virology and Gene Therapy, KU Leuven, Leuven 3000, Flanders, Belgium.
authors.forename: Rik
authors.initials: R
authors.lastname: Gijsbers
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D002843:Chromatin / Q000187:drug effects; D017988:Gammaretrovirus / Q000187:drug effects / Q000235:genetics / Q000472:pathogenicity; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D019427:HIV Integrase / Q000378:metabolism; D019428:HIV Integrase Inhibitors / Q000008:administration & dosage*; D015497:HIV-1 / Q000187:drug effects / Q000472:pathogenicity; D054884:Host-Pathogen Interactions / Q000187:drug effects / Q000235:genetics; D006801:Humans; D016086:Lentivirus / Q000187:drug effects / Q000235:genetics / Q000472:pathogenicity; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D016662:Virus Integration / Q000187:drug effects / Q000235:genetics*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D002843:Chromatin; D019428:HIV Integrase Inhibitors; C504649:PSIP1 protein, human; D014157:Transcription Factors; D019427:HIV Integrase
keywords: BET proteins; LEDGF/p75; LEDGIN; integration; integration site; retrovirus