tetano
Editor, Senior Moderator
J Exp Med. 2013 Sep 2. [Epub ahead of print]
Respiratory virus-induced EGFR activation suppresses IRF1-dependent interferon λ and antiviral defense in airway epithelium.
Ueki IF, Min-Oo G, Kalinowski A, Ballon-Landa E, Lanier LL, Nadel JA, Koff JL.
Source
Department of Medicine, 2 Cardiovascular Research Institute, 3 Department of Microbiology and Immunology, and 4 Cancer Research Institute, University of California, San Francisco, San Francisco, CA 94122.
Abstract
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.
PMID:
23999497
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/23999497
Respiratory virus-induced EGFR activation suppresses IRF1-dependent interferon λ and antiviral defense in airway epithelium.
Ueki IF, Min-Oo G, Kalinowski A, Ballon-Landa E, Lanier LL, Nadel JA, Koff JL.
Source
Department of Medicine, 2 Cardiovascular Research Institute, 3 Department of Microbiology and Immunology, and 4 Cancer Research Institute, University of California, San Francisco, San Francisco, CA 94122.
Abstract
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.
PMID:
23999497
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/23999497