HIV-1 Envelope Overcomes NLRP3-Mediated Inhibition of F-Actin Polymerization for Viral Entry

被引:30
|
作者
Paoletti, Audrey [1 ,2 ,3 ,4 ]
Allouch, Awatef [1 ,2 ,3 ,4 ]
Caillet, Marina [3 ,4 ,5 ]
Saidi, Hela [6 ]
Subra, Frederic [7 ]
Nardacci, Roberta [8 ]
Wu, Qiuji [1 ,2 ,3 ,4 ]
Muradova, Zeinaf [1 ,2 ,3 ,4 ]
Voisin, Laurent [1 ,2 ,3 ,4 ]
Raza, Syed Qasim [1 ,2 ,3 ,4 ]
Law, Frederic [1 ,2 ,3 ,4 ]
Thoreau, Maxime [1 ,2 ,3 ,4 ]
Dakhli, Haithem [1 ,2 ,3 ,4 ]
Delelis, Olivier [7 ]
Poirier-Beaudouin, Beatrice [6 ]
Dereuddre-Bosquet, Nathalie [9 ,10 ]
Le Grand, Roger [9 ,10 ]
Lambotte, Olivier [9 ,11 ,12 ]
Saez-Cirion, Asier [13 ]
Pancino, Gianfranco [13 ]
Ojcius, David M. [14 ,15 ]
Solary, Eric [2 ,16 ]
Deutsch, Eric [3 ,4 ]
Piacentini, Mauro [17 ]
Gougeon, Marie-Lise [6 ]
Kroemer, Guido [5 ,18 ,19 ,20 ,21 ,22 ,23 ]
Perfettini, Jean-Luc [1 ,2 ,3 ,4 ,14 ]
机构
[1] Gustave Roussy, Cell Death & Aging Team, 114 Rue Edouard Vaillant, F-94805 Villejuif, France
[2] Gustave Roussy, INSERM U1030, Lab Mol Radiotherapy, 114 Rue Edouard Vaillant, F-94805 Villejuif, France
[3] Gustave Roussy, 114 Rue Edouard Vaillant, F-94805 Villejuif, France
[4] Univ Paris Sud Paris 11, 114 Rue Edouard Vaillant, F-94805 Villejuif, France
[5] Gustave Roussy, INSERM U848, 114 Rue Edouard Vaillant, F-94805 Villejuif, France
[6] Institut Pasteur, Antiviral Immun Biotherapy & Vaccine Unit, Infect & Epidemiol Dept, 25 Rue Dr Roux, F-75015 Paris, France
[7] Ecole Normale Super, CNRS UMR 8113 LBPA, 61 Ave President Wilson, F-94230 Cachan, France
[8] Natl Inst Infect Dis Lazzaro Spallanzani, Via Portuense 292, I-00149 Rome, Italy
[9] Ctr Immunol Viral Infect & Autoimmune Dis, INSERM U1184, Fontenay Aux Roses, France
[10] Univ Paris Sud, UMR 1184, Fontenay Aux Roses, France
[11] IDMIT, Div Immunol Virol, DSV iMETI, CEA, Fontenay Aux Roses, France
[12] Hop Univ Paris Sud, AP HP, Serv Med Interne Immunol Clin, F-94270 Le Kremlin Bicetre, France
[13] Inst Pasteur, Unite HIV Inflammat & Persistance, 25 Rue Dr Roux, F-75025 Paris, France
[14] Univ Pacific, Arthur A Dugoni Sch Dent, Dept Biomed Sci, 155 Fifth St, San Francisco, CA 94103 USA
[15] Sorbonne Paris Cite, Univ Paris Diderot, F-75013 Paris, France
[16] Gustave Roussy, INSERM U1009, 114 Rue Edouard Vaillant, F-94805 Villejuif, France
[17] Univ Roma Tor Vergata, Dept Biol, Via Ric Sci 1, I-00133 Rome, Italy
[18] Gustave Roussy, Metabol Platform, 114 Rue Edouard Vaillant, Villejuif, France
[19] Ctr Rech Cordeliers, Equipe 11 Labellise Ligue Canc, INSERM U1138, Paris, France
[20] Sorbonne Paris Cite, Univ Paris Descartes, Paris, France
[21] Univ Paris 06, Paris, France
[22] Hop Europe Georges Pompidou, AP HP, Pole Biol, Paris, France
[23] Karolinska Univ Hosp, Dept Womens & Childrens Hlth, Karolinska Inst, Stockholm, Sweden
来源
CELL REPORTS | 2019年 / 28卷 / 13期
关键词
RICH TYROSINE KINASE-2; NLRP3; INFLAMMASOME; PURINERGIC RECEPTORS; CELL; ACTIVATION; INFECTION; SRC; SUSCEPTIBILITY; CYTOSKELETON; RESTRICTION;
D O I
10.1016/j.celrep.2019.02.095
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
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.
引用
收藏
页码:3381 / +
页数:21
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