An endogenously activated antiviral state restricts SARS-CoV-2 infection in differentiated primary airway epithelial cells.
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 >5 million deaths by February 2022. To date, targeted antiviral interventions against COVID-19 are limited. The spectrum of SARS-CoV-2...
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Format: | Article |
Language: | English |
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Public Library of Science (PLoS)
2022-01-01
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Series: | PLoS ONE |
Online Access: | https://doi.org/10.1371/journal.pone.0266412 |
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author | Lindsay Broadbent Connor G G Bamford Guillermo Lopez Campos Sheerien Manzoor David Courtney Ahlam Ali Olivier Touzelet Conall McCaughey Ken Mills Ultan F Power |
author_facet | Lindsay Broadbent Connor G G Bamford Guillermo Lopez Campos Sheerien Manzoor David Courtney Ahlam Ali Olivier Touzelet Conall McCaughey Ken Mills Ultan F Power |
author_sort | Lindsay Broadbent |
collection | DOAJ |
description | 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 >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 (IFNλ1) 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 IFNλ1 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 IFNλ1 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. |
first_indexed | 2024-04-09T21:55:28Z |
format | Article |
id | doaj.art-9b1c46f94539497787c50e8bc6d4828d |
institution | Directory Open Access Journal |
issn | 1932-6203 |
language | English |
last_indexed | 2024-04-09T21:55:28Z |
publishDate | 2022-01-01 |
publisher | Public Library of Science (PLoS) |
record_format | Article |
series | PLoS ONE |
spelling | doaj.art-9b1c46f94539497787c50e8bc6d4828d2023-03-24T05:32:17ZengPublic Library of Science (PLoS)PLoS ONE1932-62032022-01-01174e026641210.1371/journal.pone.0266412An endogenously activated antiviral state restricts SARS-CoV-2 infection in differentiated primary airway epithelial cells.Lindsay BroadbentConnor G G BamfordGuillermo Lopez CamposSheerien ManzoorDavid CourtneyAhlam AliOlivier TouzeletConall McCaugheyKen MillsUltan F PowerSevere 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 >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 (IFNλ1) 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 IFNλ1 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 IFNλ1 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.https://doi.org/10.1371/journal.pone.0266412 |
spellingShingle | Lindsay Broadbent Connor G G Bamford Guillermo Lopez Campos Sheerien Manzoor David Courtney Ahlam Ali Olivier Touzelet Conall McCaughey Ken Mills Ultan F Power An endogenously activated antiviral state restricts SARS-CoV-2 infection in differentiated primary airway epithelial cells. PLoS ONE |
title | An endogenously activated antiviral state restricts SARS-CoV-2 infection in differentiated primary airway epithelial cells. |
title_full | An endogenously activated antiviral state restricts SARS-CoV-2 infection in differentiated primary airway epithelial cells. |
title_fullStr | An endogenously activated antiviral state restricts SARS-CoV-2 infection in differentiated primary airway epithelial cells. |
title_full_unstemmed | An endogenously activated antiviral state restricts SARS-CoV-2 infection in differentiated primary airway epithelial cells. |
title_short | An endogenously activated antiviral state restricts SARS-CoV-2 infection in differentiated primary airway epithelial cells. |
title_sort | endogenously activated antiviral state restricts sars cov 2 infection in differentiated primary airway epithelial cells |
url | https://doi.org/10.1371/journal.pone.0266412 |
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