tetano
Editor, Senior Moderator
iScience
. 2021 Nov 19;103478.
doi: 10.1016/j.isci.2021.103478. Online ahead of print.
Pannexin-1 channel opening is critical for COVID-19 pathogenesis
Ross Luu[SUP] 1 [/SUP], Silvana Valdebenito[SUP] 1 [/SUP], Eliana Scemes[SUP] 2 [/SUP], Antonio Cibelli[SUP] 3 [/SUP], David Spray[SUP] 3 [/SUP], Maximiliano Rovegno[SUP] 4 [/SUP], Juan Tichauer[SUP] 4 [/SUP], Andrea Cottignies-Calamarte[SUP] 5 6 [/SUP], Arielle Rosenberg[SUP] 5 6 7 [/SUP], Calude Capron[SUP] 8 [/SUP], Sandrine Belouzard[SUP] 9 [/SUP], Jean Dubuisson[SUP] 9 [/SUP], Djallali Annane[SUP] 10 11 [/SUP], Geoffroy Lorin de la Grandmaison[SUP] 12 [/SUP], Elisabeth Cramer-Bordé[SUP] 13 [/SUP], Morgane Bomsel[SUP] 14 15 [/SUP], Eliseo Eugenin[SUP] 1 [/SUP]
Affiliations
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 is 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 ATP, PGE[SUB]2[/SUB], and IL-1β release. Analysis of lung lavage and tissues indicate that Panx-1 mRNA expression is associated with increased ATP, PGE[SUB]2[/SUB], 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 is a critical contributor to SARS-CoV-2 infection and should be considered an alternative therapy.
Keywords: ACE-2, angiotensin-converting enzyme 2; ADP, adenosine diphosphate; ATP; ATP, adenosine triphosphate; BAL, bronchoalveolar lavage; BSA, bovine serum albumin; BSL3, biosafety level 3; COPD, chronic obstructive pulmonary disease; COVID-19; COVID-19, coronavirus disease 2019; Connexin; Cx, connexin; Cx43, connexin 43; DAPI, 4′,6-diamidino-2-phenylindole; ELISA, enzyme-linked immunosorbent assay; EpCam, epithelial cell adhesion molecule; Etd, ethidium bromide; FDA, Food and Drug Administration; GPCRs, G protein-coupled receptors; HIV, human immunodeficiency virus-1; IL-1β, interleukin 1 beta; Iba-1, allograft inflammatory factor 1; La+3, lanthanum; MOI, multiplicity of infection; NAD+, nicotinamide adenine dinucleotide; PGE2, prostaglandin E2; Panx-1, pannexin-1; RBC, red blood cells; RNA, ribonucleic acid; S, spike protein; SARS-CoV-2, severe acute respiratory syndrome coronavirus-2; TMPRSS2, transmembrane serine protease 2; hCoV-229E, human coronavirus 229E; lung; mRNA, messenger ribonucleic acid; purinergic.
. 2021 Nov 19;103478.
doi: 10.1016/j.isci.2021.103478. Online ahead of print.
Pannexin-1 channel opening is critical for COVID-19 pathogenesis
Ross Luu[SUP] 1 [/SUP], Silvana Valdebenito[SUP] 1 [/SUP], Eliana Scemes[SUP] 2 [/SUP], Antonio Cibelli[SUP] 3 [/SUP], David Spray[SUP] 3 [/SUP], Maximiliano Rovegno[SUP] 4 [/SUP], Juan Tichauer[SUP] 4 [/SUP], Andrea Cottignies-Calamarte[SUP] 5 6 [/SUP], Arielle Rosenberg[SUP] 5 6 7 [/SUP], Calude Capron[SUP] 8 [/SUP], Sandrine Belouzard[SUP] 9 [/SUP], Jean Dubuisson[SUP] 9 [/SUP], Djallali Annane[SUP] 10 11 [/SUP], Geoffroy Lorin de la Grandmaison[SUP] 12 [/SUP], Elisabeth Cramer-Bordé[SUP] 13 [/SUP], Morgane Bomsel[SUP] 14 15 [/SUP], Eliseo Eugenin[SUP] 1 [/SUP]
Affiliations
- PMID: 34841222
- PMCID: PMC8603863
- DOI: 10.1016/j.isci.2021.103478
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 is 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 ATP, PGE[SUB]2[/SUB], and IL-1β release. Analysis of lung lavage and tissues indicate that Panx-1 mRNA expression is associated with increased ATP, PGE[SUB]2[/SUB], 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 is a critical contributor to SARS-CoV-2 infection and should be considered an alternative therapy.
Keywords: ACE-2, angiotensin-converting enzyme 2; ADP, adenosine diphosphate; ATP; ATP, adenosine triphosphate; BAL, bronchoalveolar lavage; BSA, bovine serum albumin; BSL3, biosafety level 3; COPD, chronic obstructive pulmonary disease; COVID-19; COVID-19, coronavirus disease 2019; Connexin; Cx, connexin; Cx43, connexin 43; DAPI, 4′,6-diamidino-2-phenylindole; ELISA, enzyme-linked immunosorbent assay; EpCam, epithelial cell adhesion molecule; Etd, ethidium bromide; FDA, Food and Drug Administration; GPCRs, G protein-coupled receptors; HIV, human immunodeficiency virus-1; IL-1β, interleukin 1 beta; Iba-1, allograft inflammatory factor 1; La+3, lanthanum; MOI, multiplicity of infection; NAD+, nicotinamide adenine dinucleotide; PGE2, prostaglandin E2; Panx-1, pannexin-1; RBC, red blood cells; RNA, ribonucleic acid; S, spike protein; SARS-CoV-2, severe acute respiratory syndrome coronavirus-2; TMPRSS2, transmembrane serine protease 2; hCoV-229E, human coronavirus 229E; lung; mRNA, messenger ribonucleic acid; purinergic.