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

Valentino Bezzerri, Valentina Gentili, Martina Api, Alessia Finotti, Chiara Papi, Anna Tamanini, Christian Boni, Elena Baldisseri, Debora Olioso, Martina Duca, Erika Tedesco, Sara Leo, Monica Borgatti, Sonia Volpi, Paolo Pinton, Giulio Cabrini, Roberto Gambari, Francesco Blasi, Giuseppe Lippi, Alessandro Rimessi, Roberta Rizzo and Marco Cipolli ()
Additional contact information
Valentino Bezzerri: Azienda Ospedaliera Universitaria Integrata
Valentina Gentili: University of Ferrara
Martina Api: Azienda Ospedaliero Universitaria Ospedali Riuniti
Alessia Finotti: University of Ferrara
Chiara Papi: University of Ferrara
Anna Tamanini: Azienda Ospedaliera Universitaria Integrata
Christian Boni: Azienda Ospedaliera Universitaria Integrata
Elena Baldisseri: Azienda Ospedaliera Universitaria Integrata
Debora Olioso: University of Verona
Martina Duca: Azienda Ospedaliero Universitaria Ospedali Riuniti
Erika Tedesco: Azienda Ospedaliera Universitaria Integrata
Sara Leo: University of Ferrara
Monica Borgatti: University of Ferrara
Sonia Volpi: Azienda Ospedaliera Universitaria Integrata
Paolo Pinton: University of Ferrara
Giulio Cabrini: University of Ferrara
Roberto Gambari: University of Ferrara
Francesco Blasi: Respiratory Unit and Cystic Fibrosis Center, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico Milano
Giuseppe Lippi: University of Verona
Alessandro Rimessi: University of Ferrara
Roberta Rizzo: University of Ferrara
Marco Cipolli: Azienda Ospedaliera Universitaria Integrata

Nature Communications, 2023, vol. 14, issue 1, 1-15

Abstract: 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.

Date: 2023
References: View references in EconPapers View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-023-35862-0 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-35862-0

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-023-35862-0

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().