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Post-mitotic BET-induced reshaping of integrase quaternary structure supports wild-type MLV integration.
Borrenberghs, Doortje; Zurnic, Irena; De Wit, Flore; Acke, Aline; Dirix, Lieve; Cereseto, Anna; Debyser, Zeger; Hendrix, Jelle.
Affiliation
  • Borrenberghs D; Laboratory for Photochemistry and Spectroscopy, Department of Chemistry, KU Leuven, Celestijnenlaan 200F, B-3001 Leuven, Belgium.
  • Zurnic I; Laboratory for Molecular Virology and Gene Therapy, Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, Kapucijnenvoer 33, B-3000 Leuven, Flanders, Belgium.
  • De Wit F; Laboratory for Molecular Virology and Gene Therapy, Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, Kapucijnenvoer 33, B-3000 Leuven, Flanders, Belgium.
  • Acke A; Laboratory for Molecular Virology and Gene Therapy, Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, Kapucijnenvoer 33, B-3000 Leuven, Flanders, Belgium.
  • Dirix L; Laboratory for Photochemistry and Spectroscopy, Department of Chemistry, KU Leuven, Celestijnenlaan 200F, B-3001 Leuven, Belgium.
  • Cereseto A; Laboratory for Photochemistry and Spectroscopy, Department of Chemistry, KU Leuven, Celestijnenlaan 200F, B-3001 Leuven, Belgium.
  • Debyser Z; Laboratory for Molecular Virology and Gene Therapy, Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, Kapucijnenvoer 33, B-3000 Leuven, Flanders, Belgium.
  • Hendrix J; Center for Integrative Biology (CIBIO), University of Trento, I-38123 Trento, Italy.
Nucleic Acids Res ; 47(3): 1195-1210, 2019 02 20.
Article in En | MEDLINE | ID: mdl-30445610
The Moloney murine leukemia virus (MLV) is a prototype gammaretrovirus requiring nuclear disassembly before DNA integration. In the nucleus, integration site selection towards promoter/enhancer elements is mediated by the host factor bromo- and extraterminal domain (BET) proteins (bromodomain (Brd) proteins 2, 3 and 4). MLV-based retroviral vectors are used in gene therapy trials. In some trials leukemia occurred through integration of the MLV vector in close proximity to cellular oncogenes. BET-mediated integration is poorly understood and the nature of integrase oligomers heavily debated. Here, we created wild-type infectious MLV vectors natively incorporating fluorescent labeled IN and performed single-molecule intensity and Förster resonance energy transfer experiments. The nuclear localization of the MLV pre-integration complex neither altered the IN content, nor its quaternary structure. Instead, BET-mediated interaction of the MLV intasome with chromatin in the post-mitotic nucleus reshaped its quaternary structure.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Virus Integration / Integrases / Moloney murine leukemia virus Limits: Humans Language: En Journal: Nucleic Acids Res Year: 2019 Type: Article Affiliation country: Belgium
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Virus Integration / Integrases / Moloney murine leukemia virus Limits: Humans Language: En Journal: Nucleic Acids Res Year: 2019 Type: Article Affiliation country: Belgium