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Dynamic Oligomerization of Integrase Orchestrates HIV Nuclear Entry.

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.

SUBMITTER: Borrenberghs D

PROVIDER: S-EPMC5103197 | biostudies-literature | 2016 Nov

REPOSITORIES: biostudies-literature

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Dynamic Oligomerization of Integrase Orchestrates HIV Nuclear Entry.

Borrenberghs Doortje D Dirix Lieve L De Wit Flore F Rocha Susana S Blokken Jolien J De Houwer Stéphanie S Gijsbers Rik R Christ Frauke F Hofkens Johan J Hendrix Jelle J Debyser Zeger Z

Scientific reports 20161110

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 th ...[more]

PMID: 27830755

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Dataset Information

Dynamic Oligomerization of Integrase Orchestrates HIV Nuclear Entry.

Publications

Dynamic Oligomerization of Integrase Orchestrates HIV Nuclear Entry.

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