{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T06:10:25Z","timestamp":1790316625444,"version":"4.1.0"},"reference-count":57,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2022,1,13]],"date-time":"2022-01-13T00:00:00Z","timestamp":1642032000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"The Kim Wright Foundation","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}]},{"name":"Doherty Collaborative Grant Scheme","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The global urgency to uncover medical countermeasures to combat the COVID-19 pandemic caused by the severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) has revealed an unmet need for robust tissue culture models that faithfully recapitulate key features of human tissues and disease. Infection of the nose is considered the dominant initial site for SARS-CoV-2 infection and models that replicate this entry portal offer the greatest potential for examining and demonstrating the effectiveness of countermeasures designed to prevent or manage this highly communicable disease. Here, we test an air\u2013liquid-interface (ALI) differentiated human nasal epithelium (HNE) culture system as a model of authentic SARS-CoV-2 infection. Progenitor cells (basal cells) were isolated from nasal turbinate brushings, expanded under conditionally reprogrammed cell (CRC) culture conditions and differentiated at ALI. Differentiated cells were inoculated with different SARS-CoV-2 clinical isolates. Infectious virus release into apical washes was determined by TCID50, while infected cells were visualized by immunofluorescence and confocal microscopy. We demonstrate robust, reproducible SARS-CoV-2 infection of ALI-HNE established from different donors. Viral entry and release occurred from the apical surface, and infection was primarily observed in ciliated cells. In contrast to the ancestral clinical isolate, the Delta variant caused considerable cell damage. Successful establishment of ALI-HNE is donor dependent. ALI-HNE recapitulate key features of human SARS-CoV-2 infection of the nose and can serve as a pre-clinical model without the need for invasive collection of human respiratory tissue samples.<\/jats:p>","DOI":"10.3390\/ijms23020835","type":"journal-article","created":{"date-parts":[[2022,1,13]],"date-time":"2022-01-13T10:57:37Z","timestamp":1642071457000},"page":"835","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":40,"title":["Air-Liquid-Interface Differentiated Human Nose Epithelium: A Robust Primary Tissue Culture Model of SARS-CoV-2 Infection"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3108-8805","authenticated-orcid":false,"given":"Bang M.","family":"Tran","sequence":"first","affiliation":[{"name":"Department of Infectious Diseases, Melbourne Medical School, Faculty of Medicine, Dentistry and Health Sciences, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, VIC 3000, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5803-3222","authenticated-orcid":false,"given":"Samantha L.","family":"Grimley","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, School of Biomedical Sciences, Faculty of Medicine, Dentistry and Health Sciences, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, VIC 3000, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie L.","family":"McAuley","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, School of Biomedical Sciences, Faculty of Medicine, Dentistry and Health Sciences, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, VIC 3000, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8032-2154","authenticated-orcid":false,"given":"Abderrahman","family":"Hachani","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, School of Biomedical Sciences, Faculty of Medicine, Dentistry and Health Sciences, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, VIC 3000, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0586-621X","authenticated-orcid":false,"given":"Linda","family":"Earnest","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, School of Biomedical Sciences, Faculty of Medicine, Dentistry and Health Sciences, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, VIC 3000, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sharon L.","family":"Wong","sequence":"additional","affiliation":[{"name":"Molecular and Integrative Cystic Fibrosis Research Centre, School of Women\u2019s and Children\u2019s Health, Faculty of Medicine, University of New South Wales, Sydney, NSW 2052, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leon","family":"Caly","sequence":"additional","affiliation":[{"name":"Victorian Infectious Diseases Reference Laboratory at the Peter Doherty Institute for Infection and Immunity, Melbourne, VIC 3000, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julian","family":"Druce","sequence":"additional","affiliation":[{"name":"Victorian Infectious Diseases Reference Laboratory at the Peter Doherty Institute for Infection and Immunity, Melbourne, VIC 3000, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4485-1726","authenticated-orcid":false,"given":"Damian F. J.","family":"Purcell","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, School of Biomedical Sciences, Faculty of Medicine, Dentistry and Health Sciences, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, VIC 3000, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7255-270X","authenticated-orcid":false,"given":"David C.","family":"Jackson","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, School of Biomedical Sciences, Faculty of Medicine, Dentistry and Health Sciences, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, VIC 3000, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mike","family":"Catton","sequence":"additional","affiliation":[{"name":"Victorian Infectious Diseases Reference Laboratory at the Peter Doherty Institute for Infection and Immunity, Melbourne, VIC 3000, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8662-9840","authenticated-orcid":false,"given":"Cameron J.","family":"Nowell","sequence":"additional","affiliation":[{"name":"Imaging, FACS and Analysis Core, Monash Institute of Pharmaceutical Sciences, Faculty of Pharmacy and Pharmaceutical Sciences, Monash University, Parkville, VIC 3052, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Leonie","sequence":"additional","affiliation":[{"name":"Melbourne Histology Platform, School of Biomedical Sciences, Faculty of Medicine, Dentistry and Health Sciences, The University of Melbourne, Parkville, VIC 3010, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Georgia","family":"Deliyannis","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, School of Biomedical Sciences, Faculty of Medicine, Dentistry and Health Sciences, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, VIC 3000, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1144-5411","authenticated-orcid":false,"given":"Shafagh A.","family":"Waters","sequence":"additional","affiliation":[{"name":"Molecular and Integrative Cystic Fibrosis Research Centre, School of Women\u2019s and Children\u2019s Health, Faculty of Medicine, University of New South Wales, Sydney, NSW 2052, Australia"},{"name":"School of Women\u2019s and Children\u2019s Health, Faculty of Medicine and Health, University of New South Wales, Sydney, NSW 2052, Australia"},{"name":"Department of Respiratory Medicine, Sydney Children\u2019s Hospital, Randwick, NSW 2031, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph","family":"Torresi","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, School of Biomedical Sciences, Faculty of Medicine, Dentistry and Health Sciences, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, VIC 3000, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8607-4849","authenticated-orcid":false,"given":"Elizabeth","family":"Vincan","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Melbourne Medical School, Faculty of Medicine, Dentistry and Health Sciences, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, VIC 3000, Australia"},{"name":"Victorian Infectious Diseases Reference Laboratory at the Peter Doherty Institute for Infection and Immunity, Melbourne, VIC 3000, Australia"},{"name":"Curtin Medical School, Curtin University, Perth, WA 6102, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,1,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"844","DOI":"10.1001\/jama.2020.1166","article-title":"Estimated Research and Development Investment Needed to Bring a New Medicine to Market, 2009\u20132018","volume":"323","author":"Wouters","year":"2020","journal-title":"J. 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