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Respiratory virus–induced EGFR activation suppresses IRF1-dependent interferon λ and antiviral defense in airway epithelium
Viruses suppress host responses to increase infection, and understanding these mechanisms has provided insights into cellular signaling and led to novel therapies. Many viruses (e.g., Influenza virus, Rhinovirus [RV], Cytomegalovirus, Epstein-Barr virus, and Hepatitis C virus) activate epithelial ep...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Rockefeller University Press
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3782052/ https://www.ncbi.nlm.nih.gov/pubmed/23999497 http://dx.doi.org/10.1084/jem.20121401 |
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author | Ueki, Iris F. Min-Oo, Gundula Kalinowski, April Ballon-Landa, Eric Lanier, Lewis L. Nadel, Jay A. Koff, Jonathan L. |
author_facet | Ueki, Iris F. Min-Oo, Gundula Kalinowski, April Ballon-Landa, Eric Lanier, Lewis L. Nadel, Jay A. Koff, Jonathan L. |
author_sort | Ueki, Iris F. |
collection | PubMed |
description | Viruses suppress host responses to increase infection, and understanding these mechanisms has provided insights into cellular signaling and led to novel therapies. Many viruses (e.g., Influenza virus, Rhinovirus [RV], Cytomegalovirus, Epstein-Barr virus, and Hepatitis C virus) activate epithelial epidermal growth factor receptor (EGFR), a tyrosine kinase receptor, but the role of EGFR in viral pathogenesis is not clear. Interferon (IFN) signaling is a critical innate antiviral host response and recent experiments have implicated IFN-λ, a type III IFN, as the most significant IFN for mucosal antiviral immune responses. Despite the importance of IFN-λ in epithelial antiviral responses, the role and mechanisms of epithelial IFN-λ signaling have not been fully elucidated. We report that respiratory virus-induced EGFR activation suppresses endogenous airway epithelial antiviral signaling. We found that Influenza virus– and RV-induced EGFR activation suppressed IFN regulatory factor (IRF) 1–induced IFN-λ production and increased viral infection. In addition, inhibition of EGFR during viral infection augmented IRF1 and IFN-λ, which resulted in decreased viral titers in vitro and in vivo. These findings describe a novel mechanism that viruses use to suppress endogenous antiviral defenses, and provide potential targets for future therapies. |
format | Online Article Text |
id | pubmed-3782052 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-37820522014-03-23 Respiratory virus–induced EGFR activation suppresses IRF1-dependent interferon λ and antiviral defense in airway epithelium Ueki, Iris F. Min-Oo, Gundula Kalinowski, April Ballon-Landa, Eric Lanier, Lewis L. Nadel, Jay A. Koff, Jonathan L. J Exp Med Brief Definitive Report Viruses suppress host responses to increase infection, and understanding these mechanisms has provided insights into cellular signaling and led to novel therapies. Many viruses (e.g., Influenza virus, Rhinovirus [RV], Cytomegalovirus, Epstein-Barr virus, and Hepatitis C virus) activate epithelial epidermal growth factor receptor (EGFR), a tyrosine kinase receptor, but the role of EGFR in viral pathogenesis is not clear. Interferon (IFN) signaling is a critical innate antiviral host response and recent experiments have implicated IFN-λ, a type III IFN, as the most significant IFN for mucosal antiviral immune responses. Despite the importance of IFN-λ in epithelial antiviral responses, the role and mechanisms of epithelial IFN-λ signaling have not been fully elucidated. We report that respiratory virus-induced EGFR activation suppresses endogenous airway epithelial antiviral signaling. We found that Influenza virus– and RV-induced EGFR activation suppressed IFN regulatory factor (IRF) 1–induced IFN-λ production and increased viral infection. In addition, inhibition of EGFR during viral infection augmented IRF1 and IFN-λ, which resulted in decreased viral titers in vitro and in vivo. These findings describe a novel mechanism that viruses use to suppress endogenous antiviral defenses, and provide potential targets for future therapies. The Rockefeller University Press 2013-09-23 /pmc/articles/PMC3782052/ /pubmed/23999497 http://dx.doi.org/10.1084/jem.20121401 Text en © 2013 Ueki et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/). |
spellingShingle | Brief Definitive Report Ueki, Iris F. Min-Oo, Gundula Kalinowski, April Ballon-Landa, Eric Lanier, Lewis L. Nadel, Jay A. Koff, Jonathan L. Respiratory virus–induced EGFR activation suppresses IRF1-dependent interferon λ and antiviral defense in airway epithelium |
title | Respiratory virus–induced EGFR activation suppresses IRF1-dependent interferon λ and antiviral defense in airway epithelium |
title_full | Respiratory virus–induced EGFR activation suppresses IRF1-dependent interferon λ and antiviral defense in airway epithelium |
title_fullStr | Respiratory virus–induced EGFR activation suppresses IRF1-dependent interferon λ and antiviral defense in airway epithelium |
title_full_unstemmed | Respiratory virus–induced EGFR activation suppresses IRF1-dependent interferon λ and antiviral defense in airway epithelium |
title_short | Respiratory virus–induced EGFR activation suppresses IRF1-dependent interferon λ and antiviral defense in airway epithelium |
title_sort | respiratory virus–induced egfr activation suppresses irf1-dependent interferon λ and antiviral defense in airway epithelium |
topic | Brief Definitive Report |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3782052/ https://www.ncbi.nlm.nih.gov/pubmed/23999497 http://dx.doi.org/10.1084/jem.20121401 |
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