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Article Dans Une Revue Frontiers in Immunology Année : 2023

The purinergic receptor P2X7 and the NLRP3 inflammasome are druggable host factors required for SARS-CoV-2 infection

1 RaMo-IT - Radiothérapie Moléculaire et Innovation Thérapeutique
2 IGR - Institut Gustave Roussy
3 National Institute for Infectious Diseases "Lazzaro Spallanzani"
4 SCIUHS - Saint Camillus International University of Health Sciences [Rome, Italy]
5 NH TherAguix SA [Meylan]
6 LBPA - Laboratoire de biologie et pharmacologie appliquée
7 IDA - Institut d'Alembert
8 CNR - Pisa - Pisa Research Area - National Research Council [Pise] (Italian National Research Council )
9 SNS - Scuola Normale Superiore di Pisa
10 University of Pisa - Università di Pisa
11 SGCSR (U_1274 / UMR_E_008) - Stabilité génétique, cellules souches et radiations
12 UGRA / SETA - CEA [Fontenay-aux-Roses]
13 IMVA-HB - Immunologie des maladies virales, auto-immunes, hématologiques et bactériennes
14 IDMIT - Infectious Diseases Models for Innovative Therapies
15 Hôpital Bicêtre [AP-HP, Le Kremlin-Bicêtre]
16 AMMICa - Analyse moléculaire, modélisation et imagerie de la maladie cancéreuse
17 Laboratoire d’Immunomonitoring en Oncologie (LIO)
18 Faculté de Pharmacie [Châtenay-Malabry]
19 UMR 8200 - Stabilité Génétique et Oncogenèse
20 IGC - Intégrité du génome et cancers
21 Département d'hématologie [Gustave Roussy]
22 Faculté de Médecine Paris-Saclay
23 "S. Chiara" Hospital, University of Pisa,
24 Azienda Ospedaliero-Universitaria Pisana = Cisanello University Hospital [Pisa]
25 Università degli Studi di Roma Tor Vergata [Roma, Italia] = University of Rome Tor Vergata [Rome, Italy] = Université de Rome Tor Vergata [Rome, Italie]

Résumé

Abstract Purinergic receptors and NOD-like receptor protein 3 (NLRP3) inflammasome regulate inflammation and viral infection, but their effects on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection remain poorly understood. Here, we report that the purinergic receptor P2X7 and NLRP3 inflammasome are cellular host factors required for SARS-CoV-2 infection. Lung autopsies from patients with severe coronavirus disease 2019 (COVID-19) reveal that NLRP3 expression is increased in host cellular targets of SARS-CoV-2 including alveolar macrophages, type II pneumocytes and syncytia arising from the fusion of infected macrophages, thus suggesting a potential role of NLRP3 and associated signaling pathways to both inflammation and viral replication. In vitro studies demonstrate that NLRP3-dependent inflammasome activation is detected upon macrophage abortive infection. More importantly, a weak activation of NLRP3 inflammasome is also detected during the early steps of SARS-CoV-2 infection of epithelial cells and promotes the viral replication in these cells. Interestingly, the purinergic receptor P2X7, which is known to control NLRP3 inflammasome activation, also favors the replication of D614G and alpha SARS-CoV-2 variants. Altogether, our results reveal an unexpected relationship between the purinergic receptor P2X7, the NLRP3 inflammasome and the permissiveness to SARS-CoV-2 infection that offers novel opportunities for COVID-19 treatment.

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Immunité innée
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inserm-04529248 , version 1 (02-04-2024)

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Déborah Lécuyer, Roberta Nardacci, Désirée Tannous, Emie Gutierrez-Mateyron, Aurélia Deva-Nathan, et al.. The purinergic receptor P2X7 and the NLRP3 inflammasome are druggable host factors required for SARS-CoV-2 infection. Frontiers in Immunology, 2023, 14, pp.1270081. ⟨10.3389/fimmu.2023.1270081⟩. ⟨inserm-04529248⟩
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