Pannexin-1 channel opening is critical for COVID-19 pathogenesis

Ross Luu; Silvana Valdebenito; Eliana Scemes; Antonio Cibelli; David C Spray; Maximiliano Rovegno; Juan Tichauer; Andrea Cottignies-Calamarte; Arielle Rosenberg; Calude Capron; Sandrine Belouzard; Jean Dubuisson; Djillali Annane; Geoffroy Lorin de la Grandmaison; Elisabeth Cramer-Bordé; Morgane Bomsel; Eliseo Eugenin

doi:10.1016/j.isci.2021.103478

Pannexin-1 channel opening is critical for COVID-19 pathogenesis

iScience. 2021 Dec 17;24(12):103478. doi: 10.1016/j.isci.2021.103478. Epub 2021 Nov 19.

Authors

Ross Luu¹, Silvana Valdebenito¹, Eliana Scemes², Antonio Cibelli³, David C Spray³, Maximiliano Rovegno⁴, Juan Tichauer⁴, Andrea Cottignies-Calamarte^{5

6}, Arielle Rosenberg^{5

6

7}, Calude Capron⁸, Sandrine Belouzard⁹, Jean Dubuisson⁹, Djillali Annane^{10

11}, Geoffroy Lorin de la Grandmaison¹², Elisabeth Cramer-Bordé¹³, Morgane Bomsel^{14

15}, Eliseo Eugenin¹

Affiliations

¹ Department of Neuroscience, Cell Biology, and Anatomy, University of Texas Medical Branch (UTMB), Research Building 17, 105 11th Street, Galveston, TX 77555, USA.
² Department of Cell Biology & Anatomy, New York Medical College, Valhalla, NY, USA.
³ Dominick P. Purpura Department of Neuroscience & Department of Medicine (Cardiology), Albert Einstein College of Medicine, New York, NY 10461, USA.
⁴ Departamento de Medicina Intensiva, Facultad de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile.
⁵ Hôpital Cochin, Service de Virologie, Hôpital Cochin (AP-HP), Paris, France.
⁶ Service d'Hématologie Hôpital Ambroise Paré (AP-HP), Boulogne-Billancourt, France.
⁷ Virologie Moléculaire et Cellulaire des Coronavirus, Centre d'infection et d'immunité de Lille, Institut Pasteur de Lille, Université de Lille, CNRS, Inserm, CHRU, 59000 Lille, France.
⁸ Service des Maladies Infectieuses, Centre Hospitalier Universitaire Raymond Poincaré, AP-HP, Garches, France.
⁹ Intensive Care Unit, Raymond Poincaré Hospital (AP-HP), Paris, France.
¹⁰ Simone Veil School of Medicine, Université of Versailles, Versailles, France.
¹¹ University Paris Saclay, Garches, France.
¹² Department of Forensic Medicine and Pathology, Versailles Saint-Quentin Université, AP-HP, Raymond Poincaré Hospital, Garches, France.
¹³ University of Versailles Saint Quentin en Yveline, Versailles, France.
¹⁴ Mucosal Entry of HIV and Mucosal Immunity, Institut Cochin, Université de Paris, Paris, France.
¹⁵ INSERM U1016, Paris, France.

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) rapidly rampaged worldwide, causing a pandemic of coronavirus disease (COVID -19), but the biology of SARS-CoV-2 remains under investigation. We demonstrate that both SARS-CoV-2 spike protein and human coronavirus 229E (hCoV-229E) or its purified S protein, one of the main viruses responsible for the common cold, induce the transient opening of Pannexin-1 (Panx-1) channels in human lung epithelial cells. However, the Panx-1 channel opening induced by SARS-CoV-2 is greater and more prolonged than hCoV-229E/S protein, resulting in an enhanced ATP, PGE₂, and IL-1β release. Analysis of lung lavages and tissues indicate that Panx-1 mRNA expression is associated with increased ATP, PGE₂, and IL-1β levels. Panx-1 channel opening induced by SARS-CoV-2 spike protein is angiotensin-converting enzyme 2 (ACE-2), endocytosis, and furin dependent. Overall, we demonstrated that Panx-1 channel is a critical contributor to SARS-CoV-2 infection and should be considered as an alternative therapy.

Keywords: Cell biology; Molecular physiology; Virology.

Abstract

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