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

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

Research output: Contribution to journal › Article › peer-review

30 Scopus citations

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.

Original language	English (US)
Article number	103478
Journal	iScience
Volume	24
Issue number	12
DOIs	https://doi.org/10.1016/j.isci.2021.103478
State	Published - Dec 17 2021

Keywords

Cell biology
Molecular physiology
Virology

ASJC Scopus subject areas

General

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10.1016/j.isci.2021.103478

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Luu, R., Valdebenito, S., Scemes, E., Cibelli, A., Spray, D. C., Rovegno, M., Tichauer, J., Cottignies-Calamarte, A., Rosenberg, A., Capron, C., Belouzard, S., Dubuisson, J., Annane, D., de la Grandmaison, G. L., Cramer-Bordé, E., Bomsel, M., & Eugenin, E. (2021). Pannexin-1 channel opening is critical for COVID-19 pathogenesis. iScience, 24(12), Article 103478. https://doi.org/10.1016/j.isci.2021.103478

Luu, R, Valdebenito, S, Scemes, E, Cibelli, A, Spray, DC, Rovegno, M, Tichauer, J, Cottignies-Calamarte, A, Rosenberg, A, Capron, C, Belouzard, S, Dubuisson, J, Annane, D, de la Grandmaison, GL, Cramer-Bordé, E, Bomsel, M & Eugenin, E 2021, 'Pannexin-1 channel opening is critical for COVID-19 pathogenesis', iScience, vol. 24, no. 12, 103478. https://doi.org/10.1016/j.isci.2021.103478

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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.",

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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

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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.

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

Abstract

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