Abstract
SummarySevere 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.
Highlights
Viruses have evolved to use host-encoded proteins to facilitate infection, replication, and associated pathogenesis (Konig et al, 2008; Krupovic et al, 2018; Pillay, 2020; Walsh and Mohr, 2011; Zhou et al, 2017)
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 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
Summary
Viruses have evolved to use host-encoded proteins to facilitate infection, replication, and associated pathogenesis (Konig et al, 2008; Krupovic et al, 2018; Pillay, 2020; Walsh and Mohr, 2011; Zhou et al, 2017). In severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), several host proteins have been described, but far more research is required to fully understand the mechanism of viral entry, replication, and pathogenesis, as well as vaccine evaluation (Bao et al, 2020; Hartenian et al, 2020; Tay et al, 2020; V’Kovski et al, 2021; Yuki et al, 2020). Our data demonstrated that SARS-CoV-2 uses Pannexin-1 (Panx-1) channels to mediate infection and associated inflammation
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