The role of epidermal growth factor receptor (EGFR) signaling in SARS coronavirus-induced pulmonary fibrosis

Antiviral Res. 2017 Jul:143:142-150. doi: 10.1016/j.antiviral.2017.03.022. Epub 2017 Apr 5.

Abstract

Many survivors of the 2003 outbreak of severe acute respiratory syndrome (SARS) developed residual pulmonary fibrosis with increased severity seen in older patients. Autopsies of patients that died from SARS also showed fibrosis to varying extents. Pulmonary fibrosis can be occasionally seen as a consequence to several respiratory viral infections but is much more common after a SARS coronavirus (SARS-CoV) infection. Given the threat of future outbreaks of severe coronavirus disease, including Middle East respiratory syndrome (MERS), it is important to understand the mechanisms responsible for pulmonary fibrosis, so as to support the development of therapeutic countermeasures and mitigate sequelae of infection. In this article, we summarize pulmonary fibrotic changes observed after a SARS-CoV infection, discuss the extent to which other respiratory viruses induce fibrosis, describe available animal models to study the development of SARS-CoV induced fibrosis and review evidence that pulmonary fibrosis is caused by a hyperactive host response to lung injury mediated by epidermal growth factor receptor (EGFR) signaling. We summarize work from our group and others indicating that inhibiting EGFR signaling may prevent an excessive fibrotic response to SARS-CoV and other respiratory viral infections and propose directions for future research.

Keywords: EGFR; Fibrosis; SARS-CoV; Wound healing.

Publication types

  • Review

MeSH terms

  • Animals
  • Disease Models, Animal
  • ErbB Receptors / metabolism
  • ErbB Receptors / physiology*
  • Host-Pathogen Interactions
  • Humans
  • Lung Injury / pathology
  • Lung Injury / virology
  • Mice
  • Pathology, Molecular
  • Pulmonary Fibrosis / etiology*
  • Pulmonary Fibrosis / metabolism
  • Pulmonary Fibrosis / pathology
  • Pulmonary Fibrosis / virology*
  • Severe Acute Respiratory Syndrome / complications*
  • Severe Acute Respiratory Syndrome / metabolism
  • Severe Acute Respiratory Syndrome / pathology
  • Severe Acute Respiratory Syndrome / virology
  • Severe acute respiratory syndrome-related coronavirus / pathogenicity*
  • Severe acute respiratory syndrome-related coronavirus / physiology*
  • Signal Transduction / physiology*
  • Wound Healing / physiology

Substances

  • EGFR protein, mouse
  • ErbB Receptors