{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T23:59:18Z","timestamp":1787788758184,"version":"build-2784847793"},"reference-count":46,"publisher":"Public Library of Science (PLoS)","issue":"4","license":[{"start":{"date-parts":[[2022,4,18]],"date-time":"2022-04-18T00:00:00Z","timestamp":1650240000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"UKRI\/NIHR","award":["MC_PC_19057"],"award-info":[{"award-number":["MC_PC_19057"]}]},{"name":"Public Health Agency HSCNI R&D Division","award":["COM\/5613\/20"],"award-info":[{"award-number":["COM\/5613\/20"]}]},{"name":"UKRI\/NIHR","award":["MC_PC_19057"],"award-info":[{"award-number":["MC_PC_19057"]}]},{"name":"Public Health Agency HSCNI R&D Division","award":["COM\/5613\/20"],"award-info":[{"award-number":["COM\/5613\/20"]}]},{"name":"Public Health Agency HSCNI R&D Division","award":["COM\/5613\/20"],"award-info":[{"award-number":["COM\/5613\/20"]}]},{"name":"Public Health Agency HSCNI R&D Division","award":["COM\/5613\/20"],"award-info":[{"award-number":["COM\/5613\/20"]}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the cause of the coronavirus disease-19 (COVID-19) pandemic, was identified in late 2019 and caused &gt;5 million deaths by February 2022. To date, targeted antiviral interventions against COVID-19 are limited. The spectrum of SARS-CoV-2 infection ranges from asymptomatic to fatal disease. However, the reasons for varying outcomes to SARS-CoV-2 infection are yet to be elucidated. Here we show that an endogenously activated interferon lambda (IFN\u03bb1) pathway leads to resistance against SARS-CoV-2 infection. Using a well-differentiated primary nasal epithelial cell (WD-PNEC) culture model derived from multiple adult donors, we discovered that susceptibility to SARS-CoV-2 infection, but not respiratory syncytial virus (RSV) infection, varied. One of four donors was resistant to SARS-CoV-2 infection. High baseline IFN\u03bb1 expression levels and associated interferon stimulated genes correlated with resistance to SARS-CoV-2 infection. Inhibition of the JAK\/STAT pathway in WD-PNECs with high endogenous IFN\u03bb1 secretion resulted in higher SARS-CoV-2 titres. Conversely, prophylactic IFN\u03bb treatment of WD-PNECs susceptible to infection resulted in reduced viral titres. An endogenously activated IFN\u03bb response, possibly due to genetic differences, may be one explanation for the differences in susceptibility to SARS-CoV-2 infection in humans. Importantly, our work supports the continued exploration of IFN\u03bb as a potential pharmaceutical against SARS-CoV-2 infection.<\/jats:p>","DOI":"10.1371\/journal.pone.0266412","type":"journal-article","created":{"date-parts":[[2022,4,18]],"date-time":"2022-04-18T13:29:57Z","timestamp":1650288597000},"page":"e0266412","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":25,"title":["An endogenously activated antiviral state restricts SARS-CoV-2 infection in differentiated primary airway epithelial cells"],"prefix":"10.1371","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8755-6946","authenticated-orcid":true,"given":"Lindsay","family":"Broadbent","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Connor G. 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