{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,30]],"date-time":"2026-03-30T08:08:28Z","timestamp":1774858108857,"version":"3.50.1"},"reference-count":76,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2024,6,4]],"date-time":"2024-06-04T00:00:00Z","timestamp":1717459200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Department of Neuroscience, Biomedicine and Movement Sciences of the University of Verona"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>SARS-CoV-2 infection has been recently shown to induce cellular senescence in vivo. A senescence-like phenotype has been reported in cystic fibrosis (CF) cellular models. Since the previously published data highlighted a low impact of SARS-CoV-2 on CFTR-defective cells, here we aimed to investigate the senescence hallmarks in SARS-CoV-2 infection in the context of a loss of CFTR expression\/function. We infected WT and CFTR KO 16HBE14o-cells with SARS-CoV-2 and analyzed both the p21 and Ki67 expression using immunohistochemistry and viral and p21 gene expression using real-time PCR. Prior to SARS-CoV-2 infection, CFTR KO cells displayed a higher p21 and lower Ki67 expression than WT cells. We detected lipid accumulation in CFTR KO cells, identified as lipolysosomes and residual bodies at the subcellular\/ultrastructure level. After SARS-CoV-2 infection, the situation reversed, with low p21 and high Ki67 expression, as well as reduced viral gene expression in CFTR KO cells. Thus, the activation of cellular senescence pathways in CFTR-defective cells was reversed by SARS-CoV-2 infection while they were activated in CFTR WT cells. These data uncover a different response of CF and non-CF bronchial epithelial cell models to SARS-CoV-2 infection and contribute to uncovering the molecular mechanisms behind the reduced clinical impact of COVID-19 in CF patients.<\/jats:p>","DOI":"10.3390\/ijms25116185","type":"journal-article","created":{"date-parts":[[2024,6,4]],"date-time":"2024-06-04T07:39:49Z","timestamp":1717486789000},"page":"6185","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Loss of CFTR Reverses Senescence Hallmarks in SARS-CoV-2 Infected Bronchial Epithelial Cells"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6919-7169","authenticated-orcid":false,"given":"Flavia","family":"Merigo","sequence":"first","affiliation":[{"name":"Anatomy and Histology Section, Department of Neurosciences, Biomedicine and Movement Sciences, University of Verona, 37134 Verona, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-1044-3109","authenticated-orcid":false,"given":"Anna","family":"Lagni","sequence":"additional","affiliation":[{"name":"Microbiology Section, Department of Diagnostic and Public Health, University of Verona, 37134 Verona, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9623-6859","authenticated-orcid":false,"given":"Federico","family":"Boschi","sequence":"additional","affiliation":[{"name":"Department of Engineering for Innovation Medicine, University of Verona, 37134 Verona, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paolo","family":"Bernardi","sequence":"additional","affiliation":[{"name":"Anatomy and Histology Section, Department of Neurosciences, Biomedicine and Movement Sciences, University of Verona, 37134 Verona, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anita","family":"Conti","sequence":"additional","affiliation":[{"name":"Anatomy and Histology Section, Department of Neurosciences, Biomedicine and Movement Sciences, University of Verona, 37134 Verona, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1017-6440","authenticated-orcid":false,"given":"Roberto","family":"Plebani","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Medicine, Center for Advanced Studies and Technology (CAST), Department of Medical, Oral and Biotechnological Sciences, \u201cG. d\u2019Annunzio\u201d University of Chieti-Pescara, 66100 Chieti, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mario","family":"Romano","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Medicine, Center for Advanced Studies and Technology (CAST), Department of Medical, Oral and Biotechnological Sciences, \u201cG. d\u2019Annunzio\u201d University of Chieti-Pescara, 66100 Chieti, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2739-4014","authenticated-orcid":false,"given":"Claudio","family":"Sorio","sequence":"additional","affiliation":[{"name":"General Pathology Section, Department of Medicine, University of Verona, 37134 Verona, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5746-3810","authenticated-orcid":false,"given":"Virginia","family":"Lotti","sequence":"additional","affiliation":[{"name":"Microbiology Section, Department of Diagnostic and Public Health, University of Verona, 37134 Verona, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrea","family":"Sbarbati","sequence":"additional","affiliation":[{"name":"Anatomy and Histology Section, Department of Neurosciences, Biomedicine and Movement Sciences, University of Verona, 37134 Verona, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,6,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e52243","DOI":"10.15252\/embr.202052243","article-title":"The struggle of a good friend getting old: Cellular senescence in viral responses and therapy","volume":"22","author":"Kohli","year":"2021","journal-title":"EMBO Rep."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"37007","DOI":"10.1038\/srep37007","article-title":"Cell senescence is an antiviral defense mechanism","volume":"6","author":"Guerra","year":"2016","journal-title":"Sci. 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