An endogenously activated antiviral state restricts SARS-CoV-2 infection in differentiated primary airway epithelial cells
| Autor: | Connor G. G. Bamford, Conall McCaughey, Sheerien Manzoor, Lindsay Broadbent, Ultan F. Power, Ahlam A. Ali, David G. Courtney, Olivier Touzelet, Ken I. Mills, Guillermo Lopez Campos |
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| Rok vydání: | 2022 |
| Předmět: |
STAT Transcription Factors/metabolism
viruses Endogeny Antiviral Agents/pharmacology Respiratory Syncytial Virus Infections medicine.disease_cause Antiviral Agents Asymptomatic Virus Interferon medicine Humans Secretion Respiratory system skin and connective tissue diseases Janus Kinases Coronavirus Multidisciplinary SARS-CoV-2 business.industry fungi COVID-19 JAK-STAT signaling pathway virus diseases Epithelial Cells Virology Epithelial Cells/metabolism body regions STAT Transcription Factors Janus Kinases/metabolism Interferons medicine.symptom business Interferons/metabolism Signal Transduction medicine.drug |
| Zdroj: | Broadbent, L, Bamford, C G G, Lopez Campos, G, Manzoor, S, Courtney, D, Ali, A, Touzelet, O, McCaughey, C, Mills, K & Power, U F 2022, ' An endogenously activated antiviral state restricts SARS-CoV-2 infection in differentiated primary airway epithelial cells ', PLoS ONE, vol. 17, no. 4, e0266412 . https://doi.org/10.1371/journal.pone.0266412 |
| ISSN: | 1932-6203 |
| DOI: | 10.1371/journal.pone.0266412 |
| Popis: | 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 went on to cause over 3.3 million deaths in 15 months. 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 (IFNλ) pathway leads to resistance against SARS-CoV-2 infection. Using a well-differentiated primary nasal epithelial cell (WD-PNEC) model 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 IFNλ 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 IFNλ secretion resulted in higher SARS-CoV-2 titres. Conversely, prophylactic IFNλ treatment of WD-PNECs susceptible to infection resulted in reduced viral titres. An endogenously activated IFNλ 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 IFNλ as a potential pharmaceutical against SARS-CoV-2 infection. |
| Databáze: | OpenAIRE |
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