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
Affiliations
Ross Luu
Department of Neuroscience, Cell Biology, and Anatomy, University of Texas Medical Branch (UTMB), Research Building 17, 105 11th Street, Galveston, TX 77555, USA
Silvana Valdebenito
Department of Neuroscience, Cell Biology, and Anatomy, University of Texas Medical Branch (UTMB), Research Building 17, 105 11th Street, Galveston, TX 77555, USA
Eliana Scemes
Department of Cell Biology & Anatomy, New York Medical College, Valhalla, NY, USA
Antonio Cibelli
Dominick P. Purpura Department of Neuroscience & Department of Medicine (Cardiology), Albert Einstein College of Medicine, New York, NY 10461, USA
David C. Spray
Dominick P. Purpura Department of Neuroscience & Department of Medicine (Cardiology), Albert Einstein College of Medicine, New York, NY 10461, USA
Maximiliano Rovegno
Departamento de Medicina Intensiva, Facultad de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile
Juan Tichauer
Departamento de Medicina Intensiva, Facultad de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile
Andrea Cottignies-Calamarte
Hôpital Cochin, Service de Virologie, Hôpital Cochin (AP-HP), Paris, France; Service d’Hématologie Hôpital Ambroise Paré (AP-HP), Boulogne-Billancourt, France
Arielle Rosenberg
Hôpital Cochin, Service de Virologie, Hôpital Cochin (AP-HP), Paris, France; Service d’Hématologie Hôpital Ambroise Paré (AP-HP), Boulogne-Billancourt, France; 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
Calude Capron
Service des Maladies Infectieuses, Centre Hospitalier Universitaire Raymond Poincaré, AP-HP, Garches, France
Sandrine Belouzard
Intensive Care Unit, Raymond Poincaré Hospital (AP-HP), Paris, France
Jean Dubuisson
Intensive Care Unit, Raymond Poincaré Hospital (AP-HP), Paris, France
Djillali Annane
Simone Veil School of Medicine, Université of Versailles, Versailles, France; University Paris Saclay, Garches, France
Geoffroy Lorin de la Grandmaison
Department of Forensic Medicine and Pathology, Versailles Saint-Quentin Université, AP-HP, Raymond Poincaré Hospital, Garches, France
Elisabeth Cramer-Bordé
University of Versailles Saint Quentin en Yveline, Versailles, France
Morgane Bomsel
Mucosal Entry of HIV and Mucosal Immunity, Institut Cochin, Université de Paris, Paris, France; INSERM U1016, Paris, France
Eliseo Eugenin
Department of Neuroscience, Cell Biology, and Anatomy, University of Texas Medical Branch (UTMB), Research Building 17, 105 11th Street, Galveston, TX 77555, USA; Corresponding author
Summary: 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.
