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Nat Commun. 2015 Mar 6;6:6483. doi: 10.1038/ncomms7483.

Chromatin organization at the nuclear pore favours HIV replication.

Author information

1
Institut Pasteur, Unité Imagerie et Modélisation, CNRS 3691, Paris 75015, France.
2
Institut Pasteur, Unité Virus et Immunité Unité, CNRS 3015, Paris 75015, France.
3
Vita-Salute San Raffaele University Centre for Statistics in the Biomedical Sciences, Milan 20132, Italy.
4
Institute for Biomedical Technologies (ITB), CNR, via F.lli Cervi 93, Segrate 20090, Italy.
5
Institut Pasteur, Unité Virologie Moléculaire et Vaccinologie, CNRS 3569, Paris 75015, France.
6
Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, New York 10461, USA.

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.

PMID:
25744187
PMCID:
PMC4366494
DOI:
10.1038/ncomms7483
[Indexed for MEDLINE]
Free PMC Article

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