TY - JOUR
T1 - Pannexin-1 channel opening is critical for COVID-19 pathogenesis
AU - Luu, Ross
AU - Valdebenito, Silvana
AU - Scemes, Eliana
AU - Cibelli, Antonio
AU - Spray, David C.
AU - Rovegno, Maximiliano
AU - Tichauer, Juan
AU - Cottignies-Calamarte, Andrea
AU - Rosenberg, Arielle
AU - Capron, Calude
AU - Belouzard, Sandrine
AU - Dubuisson, Jean
AU - Annane, Djillali
AU - de la Grandmaison, Geoffroy Lorin
AU - Cramer-Bordé, Elisabeth
AU - Bomsel, Morgane
AU - Eugenin, Eliseo
N1 - Publisher Copyright:
© 2021 The Author(s)
PY - 2021/12/17
Y1 - 2021/12/17
N2 - 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.
AB - 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.
KW - Cell biology
KW - Molecular physiology
KW - Virology
UR - https://www.scopus.com/pages/publications/85120422361
UR - https://www.scopus.com/pages/publications/85120422361#tab=citedBy
U2 - 10.1016/j.isci.2021.103478
DO - 10.1016/j.isci.2021.103478
M3 - Article
C2 - 34841222
AN - SCOPUS:85120422361
SN - 2589-0042
VL - 24
JO - iScience
JF - iScience
IS - 12
M1 - 103478
ER -