Chromatin organization at the nuclear pore favours HIV replication

Mickaël Lelek; Nicoletta Casartelli; Danilo Pellin; Ermanno Rizzi; Philippe Souque; Marco Severgnini; Clelia Di Serio; Thomas Fricke; Felipe Diaz-Griffero; Christophe Zimmer; Pierre Charneau; Francesca Di Nunzio

doi:10.1038/ncomms7483

Chromatin organization at the nuclear pore favours HIV replication

Mickaël Lelek, Nicoletta Casartelli, Danilo Pellin, Ermanno Rizzi, Philippe Souque, Marco Severgnini, Clelia Di Serio, Thomas Fricke, Felipe Diaz-Griffero, Christophe Zimmer, Pierre Charneau, Francesca Di Nunzio

Microbiology & Immunology

Research output: Contribution to journal › Article › peer-review

67 Scopus citations

Abstract

The molecular mechanisms that allow HIV to integrate into particular sites of the host genome are poorly understood. Here we tested if the nuclear pore complex (NPC) facilitates the targeting of HIV integration by acting on chromatin topology. We show that the integrity of the nuclear side of the NPC, which is mainly composed of Tpr, is not required for HIV nuclear import, but that Nup153 is essential. Depletion of Tpr markedly reduces HIV infectivity, but not the level of integration. HIV integration sites in Tpr-depleted cells are less associated with marks of active genes, consistent with the state of chromatin proximal to the NPC, as analysed by super-resolution microscopy. LEDGF/p75, which promotes viral integration into active genes, stabilizes Tpr at the nuclear periphery and vice versa. Our data support a model in which HIV nuclear import and integration are concerted steps, and where Tpr maintains a chromatin environment favourable for HIV replication.

Original language	English (US)
Article number	6483
Journal	Nature communications
Volume	6
DOIs	https://doi.org/10.1038/ncomms7483
State	Published - Mar 2015

ASJC Scopus subject areas

Chemistry(all)
Biochemistry, Genetics and Molecular Biology(all)
Physics and Astronomy(all)

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Chromatin organization at the nuclear pore favours HIV replication. / Lelek, Mickaël; Casartelli, Nicoletta; Pellin, Danilo; Rizzi, Ermanno; Souque, Philippe; Severgnini, Marco; Di Serio, Clelia; Fricke, Thomas; Diaz-Griffero, Felipe; Zimmer, Christophe; Charneau, Pierre; Di Nunzio, Francesca.

In: Nature communications, Vol. 6, 6483, 03.2015.

Research output: Contribution to journal › Article › peer-review

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abstract = "The molecular mechanisms that allow HIV to integrate into particular sites of the host genome are poorly understood. Here we tested if the nuclear pore complex (NPC) facilitates the targeting of HIV integration by acting on chromatin topology. We show that the integrity of the nuclear side of the NPC, which is mainly composed of Tpr, is not required for HIV nuclear import, but that Nup153 is essential. Depletion of Tpr markedly reduces HIV infectivity, but not the level of integration. HIV integration sites in Tpr-depleted cells are less associated with marks of active genes, consistent with the state of chromatin proximal to the NPC, as analysed by super-resolution microscopy. LEDGF/p75, which promotes viral integration into active genes, stabilizes Tpr at the nuclear periphery and vice versa. Our data support a model in which HIV nuclear import and integration are concerted steps, and where Tpr maintains a chromatin environment favourable for HIV replication.",

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AU - Severgnini, Marco

AU - Di Serio, Clelia

AU - Fricke, Thomas

AU - Diaz-Griffero, Felipe

AU - Zimmer, Christophe

AU - Charneau, Pierre

AU - Di Nunzio, Francesca

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