Browsing School, Graduate by Author "Venkataraman, Thiagarajan"
Overactive EGFR Signaling Leads to Lung Fibrosis After SARS-CoV InfectionVenkataraman, Thiagarajan; Frieman, Matthew B.; 0000-0003-0921-6345 (2017)SARS coronavirus (SARS-CoV) is a pathogenic respiratory virus that causes acute lung injury in humans. In turn, the host mounts a wound healing response to repair the injury. One of the major sequelae caused by SARS-CoV is pulmonary fibrosis (PF), which occurs more frequently in older patients. Fibrosis is caused by a dysregulated wound healing response and the molecular pathways underlying the development of fibrosis are not completely understood. Using mouse models of SARS-CoV pathogenesis, we have identified that the wound healing 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 HB-EGF are upregulated and exogenous addition of these ligands during infection of wildtype mice 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.