ORCiD
David M. Ojcius: 0000-0003-1461-4495
Department
Biomedical Sciences
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.
Recommended Citation
Paoletti, A.,
Allouch, A.,
Caillet, M.,
Saïdi, H.,
Subra, F.,
Nardacci, R.,
Wu, Q.,
Muradova, Z.,
Voisin, L.,
Raza, S.,
Law, F.,
Thoreau, M.,
Dakhli, H.,
Delelis, O.,
Poirier-Beaudouin, B.,
Dereuddre-Bosquet, N.,
Le Grand, R.,
Lambotte, O.,
Saez-Cirion, A.,
Pancino, G.,
Ojcius, D. M.,
Solary, E.,
Deutsch, E.,
Piacentini, M.,
Gougeon, M.,
Kroemer, G.,
&
Perfettini, J.
(2019).
HIV-1 Envelope Overcomes NLRP3-Mediated Inhibition of F-Actin Polymerization for Viral Entry.
Cell Reports, 28(13), 3381–3394.e7.
DOI: 10.1016/j.celrep.2019.02.095
https://scholarlycommons.pacific.edu/dugoni-facarticles/482
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.
