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SARS-CoV-2 viral entry and replication is impaired in Cystic Fibrosis airways due to ACE2 downregulation
by
Cabrini, Giulio
, Pinton, Paolo
, Gentili, Valentina
, Borgatti, Monica
, Api, Martina
, Cipolli, Marco
, Tedesco, Erika
, Gambari, Roberto
, Bezzerri, Valentino
, Duca, Martina
, Lippi, Giuseppe
, Rimessi, Alessandro
, Finotti, Alessia
, Papi, Chiara
, Tamanini, Anna
, Baldisseri, Elena
, Blasi, Francesco
, Olioso, Debora
, Volpi, Sonia
, Leo, Sara
, Boni, Christian
, Rizzo, Roberta
in
13/106
/ 13/21
/ 13/89
/ 14
/ 14/19
/ 38
/ 38/77
/ 42
/ 631/80/304
/ 692/699/1785/4039
/ 692/699/255/2514
/ 82/29
/ 82/80
/ ACE2
/ Angiotensin
/ Angiotensin-converting enzyme 2
/ Angiotensin-Converting Enzyme 2 - genetics
/ Angiotensin-Converting Enzyme 2 - metabolism
/ Comorbidity
/ Coronaviruses
/ COVID-19
/ Cystic fibrosis
/ Cystic Fibrosis - genetics
/ Cystic Fibrosis Transmembrane Conductance Regulator - genetics
/ Cystic Fibrosis Transmembrane Conductance Regulator - metabolism
/ Down-Regulation
/ Epithelial cells
/ Epithelium
/ Humanities and Social Sciences
/ Humans
/ Infections
/ Interleukin 6
/ Localization
/ Lung diseases
/ multidisciplinary
/ Peptidyl-dipeptidase A
/ Receptors, Virus - genetics
/ Receptors, Virus - metabolism
/ Replication
/ Respiratory tract
/ SARS-CoV-2 - physiology
/ Science
/ Science (multidisciplinary)
/ Severe acute respiratory syndrome coronavirus 2
/ Spike Glycoprotein, Coronavirus - metabolism
/ Viral diseases
/ Virus Internalization
/ Virus Replication
2023
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SARS-CoV-2 viral entry and replication is impaired in Cystic Fibrosis airways due to ACE2 downregulation
by
Cabrini, Giulio
, Pinton, Paolo
, Gentili, Valentina
, Borgatti, Monica
, Api, Martina
, Cipolli, Marco
, Tedesco, Erika
, Gambari, Roberto
, Bezzerri, Valentino
, Duca, Martina
, Lippi, Giuseppe
, Rimessi, Alessandro
, Finotti, Alessia
, Papi, Chiara
, Tamanini, Anna
, Baldisseri, Elena
, Blasi, Francesco
, Olioso, Debora
, Volpi, Sonia
, Leo, Sara
, Boni, Christian
, Rizzo, Roberta
in
13/106
/ 13/21
/ 13/89
/ 14
/ 14/19
/ 38
/ 38/77
/ 42
/ 631/80/304
/ 692/699/1785/4039
/ 692/699/255/2514
/ 82/29
/ 82/80
/ ACE2
/ Angiotensin
/ Angiotensin-converting enzyme 2
/ Angiotensin-Converting Enzyme 2 - genetics
/ Angiotensin-Converting Enzyme 2 - metabolism
/ Comorbidity
/ Coronaviruses
/ COVID-19
/ Cystic fibrosis
/ Cystic Fibrosis - genetics
/ Cystic Fibrosis Transmembrane Conductance Regulator - genetics
/ Cystic Fibrosis Transmembrane Conductance Regulator - metabolism
/ Down-Regulation
/ Epithelial cells
/ Epithelium
/ Humanities and Social Sciences
/ Humans
/ Infections
/ Interleukin 6
/ Localization
/ Lung diseases
/ multidisciplinary
/ Peptidyl-dipeptidase A
/ Receptors, Virus - genetics
/ Receptors, Virus - metabolism
/ Replication
/ Respiratory tract
/ SARS-CoV-2 - physiology
/ Science
/ Science (multidisciplinary)
/ Severe acute respiratory syndrome coronavirus 2
/ Spike Glycoprotein, Coronavirus - metabolism
/ Viral diseases
/ Virus Internalization
/ Virus Replication
2023
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SARS-CoV-2 viral entry and replication is impaired in Cystic Fibrosis airways due to ACE2 downregulation
by
Cabrini, Giulio
, Pinton, Paolo
, Gentili, Valentina
, Borgatti, Monica
, Api, Martina
, Cipolli, Marco
, Tedesco, Erika
, Gambari, Roberto
, Bezzerri, Valentino
, Duca, Martina
, Lippi, Giuseppe
, Rimessi, Alessandro
, Finotti, Alessia
, Papi, Chiara
, Tamanini, Anna
, Baldisseri, Elena
, Blasi, Francesco
, Olioso, Debora
, Volpi, Sonia
, Leo, Sara
, Boni, Christian
, Rizzo, Roberta
in
13/106
/ 13/21
/ 13/89
/ 14
/ 14/19
/ 38
/ 38/77
/ 42
/ 631/80/304
/ 692/699/1785/4039
/ 692/699/255/2514
/ 82/29
/ 82/80
/ ACE2
/ Angiotensin
/ Angiotensin-converting enzyme 2
/ Angiotensin-Converting Enzyme 2 - genetics
/ Angiotensin-Converting Enzyme 2 - metabolism
/ Comorbidity
/ Coronaviruses
/ COVID-19
/ Cystic fibrosis
/ Cystic Fibrosis - genetics
/ Cystic Fibrosis Transmembrane Conductance Regulator - genetics
/ Cystic Fibrosis Transmembrane Conductance Regulator - metabolism
/ Down-Regulation
/ Epithelial cells
/ Epithelium
/ Humanities and Social Sciences
/ Humans
/ Infections
/ Interleukin 6
/ Localization
/ Lung diseases
/ multidisciplinary
/ Peptidyl-dipeptidase A
/ Receptors, Virus - genetics
/ Receptors, Virus - metabolism
/ Replication
/ Respiratory tract
/ SARS-CoV-2 - physiology
/ Science
/ Science (multidisciplinary)
/ Severe acute respiratory syndrome coronavirus 2
/ Spike Glycoprotein, Coronavirus - metabolism
/ Viral diseases
/ Virus Internalization
/ Virus Replication
2023
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SARS-CoV-2 viral entry and replication is impaired in Cystic Fibrosis airways due to ACE2 downregulation
Journal Article
SARS-CoV-2 viral entry and replication is impaired in Cystic Fibrosis airways due to ACE2 downregulation
2023
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Overview
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.
Patients with cystic fibrosis are not reporting particularly sever outcomes upon SARS-CoV-2 infection. Here, the authors demonstrate decreased ACE2 levels is cystic fibrosis airway epithelia associated with impaired viral entry and replication.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
Subject
/ 13/21
/ 13/89
/ 14
/ 14/19
/ 38
/ 38/77
/ 42
/ 82/29
/ 82/80
/ ACE2
/ Angiotensin-converting enzyme 2
/ Angiotensin-Converting Enzyme 2 - genetics
/ Angiotensin-Converting Enzyme 2 - metabolism
/ COVID-19
/ Cystic Fibrosis Transmembrane Conductance Regulator - genetics
/ Cystic Fibrosis Transmembrane Conductance Regulator - metabolism
/ Humanities and Social Sciences
/ Humans
/ Receptors, Virus - metabolism
/ Science
/ Severe acute respiratory syndrome coronavirus 2
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