Overactive Epidermal Growth Factor Receptor Signaling Leads to Increased Fibrosis after Severe Acute Respiratory Syndrome Coronavirus Infection

Frieman, Matthew B.; Coleman, Christopher M.; Venkataraman, Thiagarajan

Abstract

© 2017 American Society for Microbiology. All Rights Reserved. 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.

Citation

Frieman, M. B., Coleman, C. M., & Venkataraman, T. (2017). Overactive Epidermal Growth Factor Receptor Signaling Leads to Increased Fibrosis after Severe Acute Respiratory Syndrome Coronavirus Infection. Journal of Virology, 91(12), https://doi.org/10.1128/jvi.00182-17

• Journal Article Type: Article
• Acceptance Date: Mar 17, 2017
• Online Publication Date: Apr 12, 2017
• Publication Date: Jun 1, 2017
• Deposit Date: Dec 17, 2019
• Journal: Journal of Virology
• Print ISSN: 0022-538X
• Electronic ISSN: 1098-5514
• Publisher: American Society for Microbiology
• Peer Reviewed: Peer Reviewed
• Volume: 91
• Issue: 12
• DOI: https://doi.org/10.1128/jvi.00182-17
• Public URL: https://nottingham-repository.worktribe.com/output/3589652
• Publisher URL: https://jvi.asm.org/content/91/12/e00182-17