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SARS-CoV-2 viral entry and replication is impaired in Cystic Fibrosis airways due to ACE2 downregulation.
Bezzerri, Valentino; Gentili, Valentina; Api, Martina; Finotti, Alessia; Papi, Chiara; Tamanini, Anna; Boni, Christian; Baldisseri, Elena; Olioso, Debora; Duca, Martina; Tedesco, Erika; Leo, Sara; Borgatti, Monica; Volpi, Sonia; Pinton, Paolo; Cabrini, Giulio; Gambari, Roberto; Blasi, Francesco; Lippi, Giuseppe; Rimessi, Alessandro; Rizzo, Roberta; Cipolli, Marco.
Afiliação
  • Bezzerri V; Cystic Fibrosis Center of Verona, Azienda Ospedaliera Universitaria Integrata, Verona, Italy.
  • Gentili V; Section of Clinical Biochemistry, University of Verona, Verona, Italy.
  • Api M; Department of Chemical and Pharmaceutical Sciences, University of Ferrara, Ferrara, Italy.
  • Finotti A; Cystic Fibrosis Center of Ancona, Azienda Ospedaliero Universitaria Ospedali Riuniti, Ancona, Italy.
  • Papi C; Department of Life Sciences and Biotechnology, University of Ferrara, Ferrara, Italy.
  • Tamanini A; Center on Innovative Therapies for Cystic Fibrosis, University of Ferrara, Ferrara, Italy.
  • Boni C; Department of Life Sciences and Biotechnology, University of Ferrara, Ferrara, Italy.
  • Baldisseri E; Section of Molecular Pathology, Azienda Ospedaliera Universitaria Integrata, Verona, Italy.
  • Olioso D; Cystic Fibrosis Center of Verona, Azienda Ospedaliera Universitaria Integrata, Verona, Italy.
  • Duca M; Cystic Fibrosis Center of Verona, Azienda Ospedaliera Universitaria Integrata, Verona, Italy.
  • Tedesco E; Section of Clinical Biochemistry, University of Verona, Verona, Italy.
  • Leo S; Cystic Fibrosis Center of Ancona, Azienda Ospedaliero Universitaria Ospedali Riuniti, Ancona, Italy.
  • Borgatti M; Cystic Fibrosis Center of Verona, Azienda Ospedaliera Universitaria Integrata, Verona, Italy.
  • Volpi S; Department of Medical Sciences, University of Ferrara, Ferrara, Italy.
  • Pinton P; Department of Life Sciences and Biotechnology, University of Ferrara, Ferrara, Italy.
  • Cabrini G; Center on Innovative Therapies for Cystic Fibrosis, University of Ferrara, Ferrara, Italy.
  • Gambari R; Cystic Fibrosis Center of Verona, Azienda Ospedaliera Universitaria Integrata, Verona, Italy.
  • Blasi F; Center on Innovative Therapies for Cystic Fibrosis, University of Ferrara, Ferrara, Italy.
  • Lippi G; Department of Medical Sciences, University of Ferrara, Ferrara, Italy.
  • Rimessi A; Department of Life Sciences and Biotechnology, University of Ferrara, Ferrara, Italy.
  • Rizzo R; Center on Innovative Therapies for Cystic Fibrosis, University of Ferrara, Ferrara, Italy.
  • Cipolli M; Department of Life Sciences and Biotechnology, University of Ferrara, Ferrara, Italy.
Nat Commun ; 14(1): 132, 2023 01 10.
Article em En | MEDLINE | ID: mdl-36627352
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.
Assuntos

Texto completo: 1 Coleções: 01-internacional Temas: Geral Base de dados: MEDLINE Assunto principal: Fibrose Cística / Internalização do Vírus / Enzima de Conversão de Angiotensina 2 / SARS-CoV-2 / COVID-19 Limite: Humans Idioma: En Revista: Nat Commun Assunto da revista: BIOLOGIA / CIENCIA Ano de publicação: 2023 Tipo de documento: Article País de afiliação: Itália

Texto completo: 1 Coleções: 01-internacional Temas: Geral Base de dados: MEDLINE Assunto principal: Fibrose Cística / Internalização do Vírus / Enzima de Conversão de Angiotensina 2 / SARS-CoV-2 / COVID-19 Limite: Humans Idioma: En Revista: Nat Commun Assunto da revista: BIOLOGIA / CIENCIA Ano de publicação: 2023 Tipo de documento: Article País de afiliação: Itália