An endogenously activated antiviral state restricts SARS-CoV-2 infection in differentiated primary airway epithelial cells Article Swipe
Lindsay Broadbent
,
Connor Bamford
,
Guillermo López–Campos
,
Sheerien Manzoor
,
David Courtney
,
Ahlam Ali
,
Olivier Touzelet
,
Conall McCaughey
,
Ken Mills
,
Ultan F. Power
·
YOU?
·
· 2022
· Open Access
·
· DOI: https://doi.org/10.1371/journal.pone.0266412
YOU?
·
· 2022
· Open Access
·
· DOI: https://doi.org/10.1371/journal.pone.0266412
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.
Related Topics
Concepts
Interferon
Virology
Biology
Immunology
Coronavirus
Asymptomatic
Virus
Viral shedding
Disease
Medicine
Coronavirus disease 2019 (COVID-19)
Infectious disease (medical specialty)
Internal medicine
Metadata
- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.1371/journal.pone.0266412
- https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0266412&type=printable
- OA Status
- gold
- Cited By
- 23
- References
- 47
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W4225985335
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
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https://openalex.org/W4225985335Canonical identifier for this work in OpenAlex
- DOI
-
https://doi.org/10.1371/journal.pone.0266412Digital Object Identifier
- Title
-
An endogenously activated antiviral state restricts SARS-CoV-2 infection in differentiated primary airway epithelial cellsWork title
- Type
-
articleOpenAlex work type
- Language
-
enPrimary language
- Publication year
-
2022Year of publication
- Publication date
-
2022-04-18Full publication date if available
- Authors
-
Lindsay Broadbent, Connor Bamford, Guillermo López–Campos, Sheerien Manzoor, David Courtney, Ahlam Ali, Olivier Touzelet, Conall McCaughey, Ken Mills, Ultan F. PowerList of authors in order
- Landing page
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https://doi.org/10.1371/journal.pone.0266412Publisher landing page
- PDF URL
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https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0266412&type=printableDirect link to full text PDF
- Open access
-
YesWhether a free full text is available
- OA status
-
goldOpen access status per OpenAlex
- OA URL
-
https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0266412&type=printableDirect OA link when available
- Concepts
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Interferon, Virology, Biology, Immunology, Coronavirus, Asymptomatic, Virus, Viral shedding, Disease, Medicine, Coronavirus disease 2019 (COVID-19), Infectious disease (medical specialty), Internal medicineTop concepts (fields/topics) attached by OpenAlex
- Cited by
-
23Total citation count in OpenAlex
- Citations by year (recent)
-
2025: 2, 2024: 6, 2023: 12, 2022: 3Per-year citation counts (last 5 years)
- References (count)
-
47Number of works referenced by this work
- Related works (count)
-
10Other works algorithmically related by OpenAlex
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| abstract_inverted_index.donors, | 93 |
| abstract_inverted_index.genetic | 173 |
| abstract_inverted_index.humans. | 188 |
| abstract_inverted_index.million | 23 |
| abstract_inverted_index.pathway | 72, 138 |
| abstract_inverted_index.primary | 82 |
| abstract_inverted_index.reasons | 50 |
| abstract_inverted_index.reduced | 162 |
| abstract_inverted_index.titres. | 150, 164 |
| abstract_inverted_index.varied. | 108 |
| abstract_inverted_index.varying | 52 |
| abstract_inverted_index.(IFNλ1) | 71 |
| abstract_inverted_index.COVID-19 | 34 |
| abstract_inverted_index.February | 26 |
| abstract_inverted_index.However, | 48 |
| abstract_inverted_index.JAK/STAT | 137 |
| abstract_inverted_index.WD-PNECs | 140, 156 |
| abstract_inverted_index.baseline | 119 |
| abstract_inverted_index.disease. | 47 |
| abstract_inverted_index.limited. | 36 |
| abstract_inverted_index.multiple | 91 |
| abstract_inverted_index.outcomes | 53 |
| abstract_inverted_index.possibly | 170 |
| abstract_inverted_index.resulted | 146, 160 |
| abstract_inverted_index.spectrum | 38 |
| abstract_inverted_index.supports | 192 |
| abstract_inverted_index.syndrome | 3 |
| abstract_inverted_index.targeted | 30 |
| abstract_inverted_index.(WD-PNEC) | 86 |
| abstract_inverted_index.activated | 68, 167 |
| abstract_inverted_index.antiviral | 31 |
| abstract_inverted_index.continued | 194 |
| abstract_inverted_index.infection | 41, 56, 159, 186 |
| abstract_inverted_index.pandemic, | 14 |
| abstract_inverted_index.potential | 200 |
| abstract_inverted_index.resistant | 114 |
| abstract_inverted_index.response, | 169 |
| abstract_inverted_index.secretion | 145 |
| abstract_inverted_index.syncytial | 104 |
| abstract_inverted_index.treatment | 154 |
| abstract_inverted_index.(COVID-19) | 13 |
| abstract_inverted_index.Inhibition | 134 |
| abstract_inverted_index.SARS-CoV-2 | 40, 55, 77, 99, 116, 132, 149, 185, 203 |
| abstract_inverted_index.associated | 124 |
| abstract_inverted_index.correlated | 128 |
| abstract_inverted_index.discovered | 95 |
| abstract_inverted_index.disease-19 | 12 |
| abstract_inverted_index.endogenous | 143 |
| abstract_inverted_index.epithelial | 84 |
| abstract_inverted_index.expression | 121 |
| abstract_inverted_index.identified | 16 |
| abstract_inverted_index.infection, | 100, 107 |
| abstract_inverted_index.infection. | 78, 117, 133, 204 |
| abstract_inverted_index.interferon | 69, 125 |
| abstract_inverted_index.resistance | 75, 130 |
| abstract_inverted_index.stimulated | 126 |
| abstract_inverted_index.Conversely, | 151 |
| abstract_inverted_index.coronavirus | 4, 11 |
| abstract_inverted_index.differences | 181 |
| abstract_inverted_index.elucidated. | 61 |
| abstract_inverted_index.explanation | 178 |
| abstract_inverted_index.exploration | 195 |
| abstract_inverted_index.respiratory | 2, 103 |
| abstract_inverted_index.susceptible | 157 |
| abstract_inverted_index.Importantly, | 189 |
| abstract_inverted_index.asymptomatic | 44 |
| abstract_inverted_index.differences, | 174 |
| abstract_inverted_index.endogenously | 67, 166 |
| abstract_inverted_index.prophylactic | 152 |
| abstract_inverted_index.(SARS-CoV-2), | 6 |
| abstract_inverted_index.interventions | 32 |
| abstract_inverted_index.pharmaceutical | 201 |
| abstract_inverted_index.susceptibility | 97, 183 |
| abstract_inverted_index.well-differentiated | 81 |
| cited_by_percentile_year.max | 99 |
| cited_by_percentile_year.min | 95 |
| corresponding_author_ids | https://openalex.org/A5022507496, https://openalex.org/A5042537374 |
| countries_distinct_count | 1 |
| institutions_distinct_count | 10 |
| corresponding_institution_ids | https://openalex.org/I126231945 |
| sustainable_development_goals[0].id | https://metadata.un.org/sdg/3 |
| sustainable_development_goals[0].score | 0.8700000047683716 |
| sustainable_development_goals[0].display_name | Good health and well-being |
| citation_normalized_percentile.value | 0.90666067 |
| citation_normalized_percentile.is_in_top_1_percent | False |
| citation_normalized_percentile.is_in_top_10_percent | True |