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Initial observations suggested lower COVID-19 rates among CF populations; however, subsequent clinical data have presented a more complex scenario. This study aimed to investigate how bronchial epithelial cells from individuals with and without CF, including various CFTR (CF transmembrane conductance regulator) mutations, respond to in vitro infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants and SARS-CoV. Comparisons with the influenza A virus (IAV) were included based on evidence that patients with CF experience heightened morbidity from IAV infection. Our findings showed that CF epithelial cells exhibited reduced replication of SARS-CoV-2, regardless of the type of CFTR mutation or SARS-CoV-2 variant, as well as the original 2003 SARS-CoV. In contrast, these cells displayed more efficient IAV replication than non-CF cells. Interestingly, the reduced susceptibility to SARS-CoV-2 in CF was not linked to the expression of ACE2 (angiotensin-converting enzyme 2) receptor or to CFTR dysfunction, as pharmacological treatments to restore CFTR function did not normalize the viral response. Both SARS-CoV-2 infection and CFTR function influenced the concentrations of certain cytokines and chemokines, although these effects were not correlated. Overall, this study reveals a unique viral response in CF epithelial cells, characterized by reduced replication for some viruses like SARS-CoV-2, while showing increased susceptibility to others, such as IAV. This research offers a new perspective on CF and viral interactions, emphasizing the need for further investigation into the mechanisms underlying these differences.<\/jats:p>","DOI":"10.1165\/rcmb.2024-0213oc","type":"journal-article","created":{"date-parts":[[2024,9,23]],"date-time":"2024-09-23T10:56:48Z","timestamp":1727089008000},"page":"308-319","update-policy":"https:\/\/doi.org\/10.1164\/crossmarkpolicies","source":"Crossref","is-referenced-by-count":4,"title":["Distinct Responses of Cystic Fibrosis Epithelial Cells to SARS-CoV-2 and Influenza A Virus"],"prefix":"10.1093","volume":"72","author":[{"given":"Isabel","family":"Pagani","sequence":"first","affiliation":[{"name":"Viral Pathogenesis and Biosafety Unit and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arianna","family":"Venturini","sequence":"additional","affiliation":[{"name":"Telethon Institute of Genetics and Medicine, Pozzuoli, Italy"},{"name":"Department of Translational Medical Sciences, University of Napoli Federico II, Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valeria","family":"Capurro","sequence":"additional","affiliation":[{"name":"Unit of Medical Genetics (UOC), IRCCS Giannina Gaslini Institute, Genoa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandro","family":"Nonis","sequence":"additional","affiliation":[{"name":"University Centre for Statistics in the Biomedical Sciences (CUSSB), Vita-Salute San Raffaele University, Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia","family":"Ghezzi","sequence":"additional","affiliation":[{"name":"Viral Pathogenesis and Biosafety Unit and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariateresa","family":"Lena","sequence":"additional","affiliation":[{"name":"Unit of Medical Genetics (UOC), IRCCS Giannina Gaslini Institute, Genoa, Italy"},{"name":"Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DINOGMI), University of Genoa, Genoa, Italy; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beatriz","family":"Alcal\u00e1-Franco","sequence":"additional","affiliation":[{"name":"Infections and Cystic Fibrosis Unit, Division of Immunology, Transplantation, and Infectious Diseases, IRCCS San Raffaele Scientific Institute, Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabrizio","family":"Gianferro","sequence":"additional","affiliation":[{"name":"Infections and Cystic Fibrosis Unit, Division of Immunology, Transplantation, and Infectious Diseases, IRCCS San Raffaele Scientific Institute, Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela","family":"Guidone","sequence":"additional","affiliation":[{"name":"Telethon Institute of Genetics and Medicine, Pozzuoli, Italy"},{"name":"Department of Translational Medical Sciences, University of Napoli Federico II, Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carla","family":"Colombo","sequence":"additional","affiliation":[{"name":"Foundation IRCCS Ca\u2019 Granda Ospedale Maggiore Policlinico, Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicoletta","family":"Pedemonte","sequence":"additional","affiliation":[{"name":"Unit of Medical Genetics (UOC), IRCCS Giannina Gaslini Institute, Genoa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandra","family":"Bragonzi","sequence":"additional","affiliation":[{"name":"Infections and Cystic Fibrosis Unit, Division of Immunology, Transplantation, and Infectious Diseases, IRCCS San Raffaele Scientific Institute, Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina","family":"Cigana","sequence":"additional","affiliation":[{"name":"Infections and Cystic Fibrosis Unit, Division of Immunology, Transplantation, and Infectious Diseases, IRCCS San Raffaele Scientific Institute, Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luis J. 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