Abstract
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.
| Original language | English |
|---|---|
| Pages (from-to) | 3381-3394.e7 |
| Journal | Cell Reports |
| Volume | 28 |
| Issue number | 13 |
| DOIs | |
| Publication status | Published - Sep 24 2019 |
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Keywords
- CBL
- HIV
- inflammasome
- NLRP3
- P2Y2
- viral entry
ASJC Scopus subject areas
- Biochemistry, Genetics and Molecular Biology(all)
Cite this
HIV-1 Envelope Overcomes NLRP3-Mediated Inhibition of F-Actin Polymerization for Viral Entry. / Paoletti, Audrey; Allouch, Awatef; Caillet, Marina; Saïdi, Hela; Subra, Frédéric; Nardacci, Roberta; Wu, Qiuji; Muradova, Zeinaf; Voisin, Laurent; Raza, Syed Qasim; Law, Frédéric; Thoreau, Maxime; Dakhli, Haithem; Delelis, Olivier; Poirier-Beaudouin, Béatrice; Dereuddre-Bosquet, Nathalie; Le Grand, Roger; Lambotte, Olivier; Saez-Cirion, Asier; Pancino, Gianfranco; Ojcius, David M.; Solary, Eric; Deutsch, Eric; Piacentini, Mauro; Gougeon, Marie Lise; Kroemer, Guido; Perfettini, Jean Luc.
In: Cell Reports, Vol. 28, No. 13, 24.09.2019, p. 3381-3394.e7.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - HIV-1 Envelope Overcomes NLRP3-Mediated Inhibition of F-Actin Polymerization for Viral Entry
AU - Paoletti, Audrey
AU - Allouch, Awatef
AU - Caillet, Marina
AU - Saïdi, Hela
AU - Subra, Frédéric
AU - Nardacci, Roberta
AU - Wu, Qiuji
AU - Muradova, Zeinaf
AU - Voisin, Laurent
AU - Raza, Syed Qasim
AU - Law, Frédéric
AU - Thoreau, Maxime
AU - Dakhli, Haithem
AU - Delelis, Olivier
AU - Poirier-Beaudouin, Béatrice
AU - Dereuddre-Bosquet, Nathalie
AU - Le Grand, Roger
AU - Lambotte, Olivier
AU - Saez-Cirion, Asier
AU - Pancino, Gianfranco
AU - Ojcius, David M.
AU - Solary, Eric
AU - Deutsch, Eric
AU - Piacentini, Mauro
AU - Gougeon, Marie Lise
AU - Kroemer, Guido
AU - Perfettini, Jean Luc
PY - 2019/9/24
Y1 - 2019/9/24
N2 - 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.
AB - 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.
KW - CBL
KW - HIV
KW - inflammasome
KW - NLRP3
KW - P2Y2
KW - viral entry
UR - http://www.scopus.com/inward/record.url?scp=85072338637&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85072338637&partnerID=8YFLogxK
U2 - 10.1016/j.celrep.2019.02.095
DO - 10.1016/j.celrep.2019.02.095
M3 - Article
AN - SCOPUS:85072338637
VL - 28
SP - 3381-3394.e7
JO - Cell Reports
JF - Cell Reports
SN - 2211-1247
IS - 13
ER -