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SARS-CoV-2 viral entry and replication is impaired in Cystic Fibrosis airways due to ACE2 downregulation

2023; Nature Portfolio; Volume: 14; Issue: 1 Linguagem: Inglês

10.1038/s41467-023-35862-0

2041-1723

Valentino Bezzerri, Valentina Gentili, Martina Api, Alessia Finotti, Chiara Papi, Anna Tamanini, Christian Boni, Elena Baldisseri, Debora Olioso, Martina Duca, Erika Tedesco, Laura S. Leo, Monica Borgatti, Sonia Volpi, Paolo Pinton, Giulio Cabrini, Roberto Gambari, Francesco Blasi, Giuseppe Lippi, Alessandro Rimessi, Roberta Rizzo, Marco Cipolli,

Respiratory viral infections research

Abstract As an inherited disorder characterized by severe pulmonary disease, cystic fibrosis could be considered a comorbidity for coronavirus disease 2019. Instead, current clinical evidence seems to be heading in the opposite direction. To clarify whether host factors expressed by the Cystic Fibrosis epithelia may influence coronavirus disease 2019 progression, here we describe the expression of SARS-CoV-2 receptors in primary airway epithelial cells. We show that angiotensin converting enzyme 2 (ACE2) expression and localization are regulated by Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) channel. Consistently, our results indicate that dysfunctional CFTR channels alter susceptibility to SARS-CoV-2 infection, resulting in reduced viral entry and replication in Cystic Fibrosis cells. Depending on the pattern of ACE2 expression, the SARS-CoV-2 spike (S) protein induced high levels of Interleukin 6 in healthy donor-derived primary airway epithelial cells, but a very weak response in primary Cystic Fibrosis cells. Collectively, these data support that Cystic Fibrosis condition may be at least partially protecting from SARS-CoV-2 infection.