Frontiers in Immunology (Oct 2023)

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

  • Déborah Lécuyer,
  • Déborah Lécuyer,
  • Roberta Nardacci,
  • Roberta Nardacci,
  • Désirée Tannous,
  • Désirée Tannous,
  • Désirée Tannous,
  • Emie Gutierrez-Mateyron,
  • Emie Gutierrez-Mateyron,
  • Aurélia Deva Nathan,
  • Aurélia Deva Nathan,
  • Frédéric Subra,
  • Cristina Di Primio,
  • Cristina Di Primio,
  • Paola Quaranta,
  • Paola Quaranta,
  • Vanessa Petit,
  • Clémence Richetta,
  • Ali Mostefa-Kara,
  • Ali Mostefa-Kara,
  • Franca Del Nonno,
  • Laura Falasca,
  • Romain Marlin,
  • Pauline Maisonnasse,
  • Julia Delahousse,
  • Julia Delahousse,
  • Juliette Pascaud,
  • Juliette Pascaud,
  • Eric Deprez,
  • Marie Naigeon,
  • Marie Naigeon,
  • Marie Naigeon,
  • Nathalie Chaput,
  • Nathalie Chaput,
  • Nathalie Chaput,
  • Angelo Paci,
  • Angelo Paci,
  • Angelo Paci,
  • Angelo Paci,
  • Véronique Saada,
  • David Ghez,
  • David Ghez,
  • Xavier Mariette,
  • Xavier Mariette,
  • Xavier Mariette,
  • Mario Costa,
  • Mario Costa,
  • Mario Costa,
  • Mauro Pistello,
  • Mauro Pistello,
  • Awatef Allouch,
  • Awatef Allouch,
  • Awatef Allouch,
  • Olivier Delelis,
  • Mauro Piacentini,
  • Mauro Piacentini,
  • Roger Le Grand,
  • Jean-Luc Perfettini,
  • Jean-Luc Perfettini

DOI
https://doi.org/10.3389/fimmu.2023.1270081
Journal volume & issue
Vol. 14

Abstract

Read online

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.

Keywords