Overactive epidermal growth factor receptor signaling leads to increased fibrosis after severe acute respiratory syndrome coronavirus infection
Date
2017Journal
Journal of VirologyPublisher
American Society for MicrobiologyType
Article
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Severe acute respiratory syndrome coronavirus (SARS-CoV) is a highly pathogenic respiratory virus that causes morbidity and mortality in humans. After infection with SARS-CoV, the acute lung injury caused by the virus must be repaired to regain lung function. A dysregulation in this wound healing process leads to fibrosis. Many survivors of SARS-CoV infection develop pulmonary fibrosis (PF), with higher prevalence in older patients. Using mouse models of SARS-CoV pathogenesis, we have identified that the wound repair pathway, controlled by the epidermal growth factor receptor (EGFR), is critical to recovery from SARS-CoV-induced tissue damage. In mice with constitutively active EGFR [EGFR(DSK5) mice], we find that SARS-CoV infection causes enhanced lung disease. Importantly, we show that during infection, the EGFR ligands amphiregulin and heparin-binding EGF-like growth factor (HB-EGF) are upregulated, and exogenous addition of these ligands during infection leads to enhanced lung disease and altered wound healing dynamics. Our data demonstrate a key role of EGFR in the host response to SARS-CoV and how it may be implicated in lung disease induced by other highly pathogenic respiratory viruses.Identifier to cite or link to this item
https://www.scopus.com/inward/record.uri?eid=2-s2.0-85019704331&doi=10.1128%2fJVI.00182-17&partnerID=40&md5=e49b36ec9090e1e411cfa8b3a7b2cc43; http://hdl.handle.net/10713/12446ae974a485f413a2113503eed53cd6c53
10.1128/JVI.00182-17
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