TY - JOUR
T1 - Chromatin organization at the nuclear pore favours HIV replication
AU - Lelek, Mickaël
AU - Casartelli, Nicoletta
AU - Pellin, Danilo
AU - Rizzi, Ermanno
AU - Souque, Philippe
AU - Severgnini, Marco
AU - Di Serio, Clelia
AU - Fricke, Thomas
AU - Diaz-Griffero, Felipe
AU - Zimmer, Christophe
AU - Charneau, Pierre
AU - Di Nunzio, Francesca
N1 - Funding Information:
This manuscript is dedicated to the memory of our colleague and friend Isabel Puig-domènech. We wish to thank Marc Lavigne and Alex Compton for critical reading of the manuscript. This work was funded by the ANRS (Agence Nationale de Recherche sur le SIDA), the Sidaction, the Pasteur Institute. C.Z. acknowledges support from Institut Pasteur, Région Ile de France (DIM Malinf), Fondation pour la Recherche Médicale (Equipe FRM 2010) and ANRS. E.R. was funded by ‘Futuro in Ricerca’ grant n° RBFR126B8I_003. F.D.G and T.F. were supported by grants NIH R01 AI087390, R21 AI102824 and R56 AI108432 to F.D.G.
Publisher Copyright:
© 2015 Macmillan Publishers Limited. All rights reserved.
PY - 2015/3
Y1 - 2015/3
N2 - 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.
AB - 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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U2 - 10.1038/ncomms7483
DO - 10.1038/ncomms7483
M3 - Article
C2 - 25744187
AN - SCOPUS:84924299957
VL - 6
JO - Nature Communications
JF - Nature Communications
SN - 2041-1723
M1 - 6483
ER -
