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Chromatin organization at the nuclear pore favours HIV replication

Author

Listed:
  • Mickaël Lelek

    (Institut Pasteur, Unité Imagerie et Modélisation, CNRS 3691)

  • Nicoletta Casartelli

    (Institut Pasteur, Unité Virus et Immunité Unité, CNRS 3015)

  • Danilo Pellin

    (Vita-Salute San Raffaele University Centre for Statistics in the Biomedical Sciences)

  • Ermanno Rizzi

    (Institute for Biomedical Technologies (ITB), CNR)

  • Philippe Souque

    (Institut Pasteur, Unité Virologie Moléculaire et Vaccinologie, CNRS 3569)

  • Marco Severgnini

    (Institute for Biomedical Technologies (ITB), CNR)

  • Clelia Di Serio

    (Vita-Salute San Raffaele University Centre for Statistics in the Biomedical Sciences)

  • Thomas Fricke

    (Albert Einstein College of Medicine)

  • Felipe Diaz-Griffero

    (Albert Einstein College of Medicine)

  • Christophe Zimmer

    (Institut Pasteur, Unité Imagerie et Modélisation, CNRS 3691)

  • Pierre Charneau

    (Institut Pasteur, Unité Virologie Moléculaire et Vaccinologie, CNRS 3569)

  • Francesca Di Nunzio

    (Institut Pasteur, Unité Virologie Moléculaire et Vaccinologie, CNRS 3569)

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.

Suggested Citation

  • Mickaël Lelek & Nicoletta Casartelli & Danilo Pellin & Ermanno Rizzi & Philippe Souque & Marco Severgnini & Clelia Di Serio & Thomas Fricke & Felipe Diaz-Griffero & Christophe Zimmer & Pierre Charneau, 2015. "Chromatin organization at the nuclear pore favours HIV replication," Nature Communications, Nature, vol. 6(1), pages 1-12, May.
  • Handle: RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms7483
    DOI: 10.1038/ncomms7483
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    Cited by:

    1. Monica Naughtin & Zofia Haftek-Terreau & Johan Xavier & Sam Meyer & Maud Silvain & Yan Jaszczyszyn & Nicolas Levy & Vincent Miele & Mohamed Salah Benleulmi & Marc Ruff & Vincent Parissi & Cédric Vaill, 2015. "DNA Physical Properties and Nucleosome Positions Are Major Determinants of HIV-1 Integrase Selectivity," PLOS ONE, Public Library of Science, vol. 10(6), pages 1-28, June.

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