tetano
Editor, Senior Moderator
PLoS One
. 2022 Apr 18;17(4):e0266412.
doi: 10.1371/journal.pone.0266412. eCollection 2022.
An endogenously activated antiviral state restricts SARS-CoV-2 infection in differentiated primary airway epithelial cells
Lindsay Broadbent[SUP] 1 [/SUP], Connor G G Bamford[SUP] 1 [/SUP], Guillermo Lopez Campos[SUP] 1 [/SUP], Sheerien Manzoor[SUP] 1 [/SUP], David Courtney[SUP] 1 [/SUP], Ahlam Ali[SUP] 1 2 [/SUP], Olivier Touzelet[SUP] 1 [/SUP], Conall McCaughey[SUP] 3 [/SUP], Ken Mills[SUP] 2 [/SUP], Ultan F Power[SUP] 1 [/SUP]
Affiliations
Abstract
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.
. 2022 Apr 18;17(4):e0266412.
doi: 10.1371/journal.pone.0266412. eCollection 2022.
An endogenously activated antiviral state restricts SARS-CoV-2 infection in differentiated primary airway epithelial cells
Lindsay Broadbent[SUP] 1 [/SUP], Connor G G Bamford[SUP] 1 [/SUP], Guillermo Lopez Campos[SUP] 1 [/SUP], Sheerien Manzoor[SUP] 1 [/SUP], David Courtney[SUP] 1 [/SUP], Ahlam Ali[SUP] 1 2 [/SUP], Olivier Touzelet[SUP] 1 [/SUP], Conall McCaughey[SUP] 3 [/SUP], Ken Mills[SUP] 2 [/SUP], Ultan F Power[SUP] 1 [/SUP]
Affiliations
- PMID: 35436306
- DOI: 10.1371/journal.pone.0266412
Abstract
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.