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

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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 ¹ , Silvana Valdebenito ¹ , Eliana Scemes ² , Antonio Cibelli ³ , David Spray ³ , Maximiliano Rovegno ⁴ , Juan Tichauer ⁴ , Andrea Cottignies-Calamarte ^{5 6} , Arielle Rosenberg ^{5 6 7} , Calude Capron ⁸ , Sandrine Belouzard ⁹ , Jean Dubuisson ⁹ , Djallali Annane ^{10 11} , Geoffroy Lorin de la Grandmaison ¹² , Elisabeth Cramer-Bordé ¹³ , Morgane Bomsel ^{14 15} , Eliseo Eugenin ¹



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, PGE₂, and IL-1β release. Analysis of lung lavage 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 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.