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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 | Source: | 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. | Document URI: | http://hdl.handle.net/1942/22838 | ISSN: | 2045-2322 | e-ISSN: | 2045-2322 | DOI: | 10.1038/srep36485 | ISI #: | 000387369300001 | Rights: | © The Author(s) 2016. This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ | Category: | A1 | Type: | Journal Contribution | Validations: | ecoom 2017 |
Appears in Collections: | Research publications |
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