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Please use this identifier to cite or link to this item: http://hdl.handle.net/1942/22838

Title: Dynamic Oligomerization of Integrase Orchestrates HIV Nuclear Entry
Authors: Borrenberghs, Doortje
Dirix, Lieve
De Wit, Flore
Rocha, Susana
Blokken, Jolien
De Houwer, Stéphanie
Gijsbers, Rik
Christ, Frauke
Hofkens, Johan
Hendrix, Jelle
Debyser, Zeger
Issue Date: 2016
Publisher: NATURE PUBLISHING GROUP
Citation: SCIENTIFIC REPORTS, 6 (Art N° 36485)
Abstract: Nuclear entry is a selective, dynamic process granting the HIV-1 pre-integration complex (PIC) access to the chromatin. Classical analysis of nuclear entry of heterogeneous viral particles only yields averaged information. We now have employed single-virus fluorescence methods to follow the fate of single viral pre-integration complexes (PICs) during infection by visualizing HIV-1 integrase (IN). Nuclear entry is associated with a reduction in the number of IN molecules in the complexes while the interaction with LEDGF/p75 enhances IN oligomerization in the nucleus. Addition of LEDGINs, small molecule inhibitors of the IN-LEDGF/p75 interaction, during virus production, prematurely stabilizes a higher-order IN multimeric state, resulting in stable IN multimers resistant to a reduction in IN content and defective for nuclear entry. This suggests that a stringent size restriction determines nuclear pore entry. Taken together, this work demonstrates the power of single-virus imaging providing crucial insights in HIV replication and enabling mechanism-of-action studies.
Notes: [Borrenberghs, Doortje; Dirix, Lieve; De Wit, Flore; Blokken, Jolien; De Houwer, Stephanie; Christ, Frauke; Debyser, Zeger] Katholieke Univ Leuven, Dept Pharmaceut & Pharmacol Sci, Lab Mol Virol & Gene Therapy, B-3000 Louvain, Belgium. [Borrenberghs, Doortje; Dirix, Lieve; Rocha, Susana; Hofkens, Johan; Hendrix, Jelle] Katholieke Univ Leuven, Dept Chem, Lab Photochem & Spect, Mol Imaging & Photon, B-3001 Heverlee, Belgium. [Gijsbers, Rik] Katholieke Univ Leuven, Dept Pharmaceut & Pharmacol Sci, Lab Viral Vector Technol & Gene Therapy, B-3000 Louvain, Belgium. [Hendrix, Jelle] Hasselt Univ, Fac Med & Life Sci, B-3590 Diepenbeek, Belgium. [Hendrix, Jelle] Hasselt Univ, Biomed Res Inst, B-3590 Diepenbeek, Belgium.
URI: http://hdl.handle.net/1942/22838
DOI: 10.1038/srep36485
ISI #: 000387369300001
ISSN: 2045-2322
Category: A1
Type: Journal Contribution
Validation: ecoom, 2017
Appears in Collections: Research publications

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