title: Functional coupling between HIV-1 integrase and the SWI/SNF chromatin remodeling complex for efficient in vitro integration into stable nucleosomes.
abstract: Establishment of stable HIV-1 infection requires the efficient integration of the retroviral genome into the host DNA. The molecular mechanism underlying the control of this process by the chromatin structure has not yet been elucidated. We show here that stably associated nucleosomes strongly inhibit in vitro two viral-end integration by decreasing the accessibility of DNA to integrase. Remodeling of the chromatinized template by the SWI/SNF complex, whose INI1 major component interacts with IN, restores and redirects the full-site integration into the stable nucleosome region. These effects are not observed after remodeling by other human remodeling factors such as SNF2H or BRG1 lacking the integrase binding protein INI1. This suggests that the restoration process depends on the direct interaction between IN and the whole SWI/SNF complex, supporting a functional coupling between the remodeling and integration complexes. Furthermore, in silico comparison between more than 40,000 non-redundant cellular integration sites selected from literature and nucleosome occupancy predictions also supports that HIV-1 integration is promoted in the genomic region of weaker intrinsic nucleosome density in the infected cell. Our data indicate that some chromatin structures can be refractory for integration and that coupling between nucleosome remodeling and HIV-1 integration is required to overcome this natural barrier.
authors.affiliation: Laboratoire MCMP, UMR 5234 CNRS-Université Victor Segalen Bordeaux 2, Bordeaux, France.
authors.forename: Paul
authors.initials: P
authors.lastname: Lesbats
authors.forename: Yair
authors.initials: Y
authors.lastname: Botbol
authors.forename: Guillaume
authors.initials: G
authors.lastname: Chevereau
authors.forename: Cédric
authors.initials: C
authors.lastname: Vaillant
authors.forename: Christina
authors.initials: C
authors.lastname: Calmels
authors.forename: Alain
authors.initials: A
authors.lastname: Arneodo
authors.forename: Marie-Line
authors.initials: ML
authors.lastname: Andreola
authors.forename: Marc
authors.initials: M
authors.lastname: Lavigne
authors.forename: Vincent
authors.initials: V
authors.lastname: Parissi
mesh_terms: D000818:Animals; D002472:Cell Transformation, Viral / Q000235:genetics; D002478:Cells, Cultured; D042002:Chromatin Assembly and Disassembly / Q000502:physiology; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism / Q000502:physiology*; D004526:Efficiency; D015967:Gene Expression Regulation, Viral; D015658:HIV Infections / Q000235:genetics / Q000378:metabolism / Q000821:virology; D019427:HIV Integrase / Q000378:metabolism / Q000502:physiology*; D006367:HeLa Cells; D006801:Humans; D008954:Models, Biological; D009707:Nucleosomes / Q000378:metabolism* / Q000821:virology*; D055550:Protein Stability; D018411:Spodoptera; D014157:Transcription Factors / Q000378:metabolism / Q000502:physiology*; D014158:Transcription, Genetic; D016662:Virus Integration / Q000502:physiology*
chemical_list: D002868:Chromosomal Proteins, Non-Histone; D009707:Nucleosomes; C445179:SWI-SNF-B chromatin-remodeling complex; D014157:Transcription Factors; D019427:HIV Integrase; C514801:p31 integrase protein, Human immunodeficiency virus 1