Authors

Audrey Paoletti, Stabilité génétique et oncogenèse
Awatef Allouch, Stabilité génétique et oncogenèse
Marina Caillet, Stabilité génétique et oncogenèse
Hela Saïdi, Institut Pasteur, Paris
Frédéric Subra, Laboratoire de Biologie et de Pharmacologie Appliquée
Roberta Nardacci, IRCCS Istituto Nazionale Malattie Infettive Lazzaro Spallanzani
Qiuji Wu, Stabilité génétique et oncogenèse
Zeinaf Muradova, Stabilité génétique et oncogenèse
Laurent Voisin, Stabilité génétique et oncogenèse
Syed Qasim Raza, Stabilité génétique et oncogenèse
Frédéric Law, Stabilité génétique et oncogenèse
Maxime Thoreau, Stabilité génétique et oncogenèse
Haithem Dakhli, Stabilité génétique et oncogenèse
Olivier Delelis, Laboratoire de Biologie et de Pharmacologie Appliquée
Béatrice Poirier-Beaudouin, Institut Pasteur, Paris
Nathalie Dereuddre-Bosquet, Centre de Recherche en Immunologie des Infections Virales et des Maladies Auto-Immunes
Roger Le Grand, Centre de Recherche en Immunologie des Infections Virales et des Maladies Auto-Immunes
Olivier Lambotte, Centre de Recherche en Immunologie des Infections Virales et des Maladies Auto-Immunes
Asier Saez-Cirion, Institut Pasteur, Paris
Gianfranco Pancino, Institut Pasteur, Paris
David M. Ojcius, University of the Pacific, CaliforniaFollow
Eric Solary, Stabilité génétique et oncogenèse
Eric Deutsch, Radiothérapie Moléculaire
Mauro Piacentini, IRCCS Istituto Nazionale Malattie Infettive Lazzaro Spallanzani
Marie Lise Gougeon, Institut Pasteur, Paris
Guido Kroemer, Stabilité génétique et oncogenèse
Jean Luc Perfettini, Stabilité génétique et oncogenèse

ORCiD

David M. Ojcius: 0000-0003-1461-4495

Document Type

Article

Publication Title

Cell Reports

ISSN

2211-1247

Volume

28

Issue

13

DOI

10.1016/j.celrep.2019.02.095

First Page

3381

Last Page

3394.e7

Publication Date

9-24-2019

Abstract

© 2019 The Author(s) Purinergic receptors and nucleotide-binding domain leucine-rich repeat containing (NLR) proteins have been shown to control viral infection. Here, we show that the NLR family member NLRP3 and the purinergic receptor P2Y2 constitutively interact and regulate susceptibility to HIV-1 infection. We found that NLRP3 acts as an inhibitory factor of viral entry that represses F-actin remodeling. The binding of the HIV-1 envelope to its host cell receptors (CD4, CXCR4, and/or CCR5) overcomes this restriction by stimulating P2Y2. Once activated, P2Y2 enhances its interaction with NLRP3 and stimulates the recruitment of the E3 ubiquitin ligase CBL to NLRP3, ultimately leading to NLRP3 degradation. NLRP3 degradation is permissive for PYK2 phosphorylation (PYK2Y402∗) and subsequent F-actin polymerization, which is required for the entry of HIV-1 into host cells. Taken together, our results uncover a mechanism by which HIV-1 overcomes NLRP3 restriction that appears essential for the accomplishment of the early steps of HIV-1 entry.

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Creative Commons Attribution 4.0 License
This work is licensed under a Creative Commons Attribution 4.0 License.

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