FIG 6.

Expression of HB-EGF and AREG is induced during SARS-CoV infection, and their exogenous overexpression can induce fibrosis. (A) Transcriptomic analysis showing expression values of the seven canonical EGFR ligands. The ligands HB-EGF and AREG are highlighted with red boxes. (B) RNA was extracted from 10- to 12-week-old wild-type and EGFR(DSK5) mice inoculated with either PBS or SARS-CoV(MA15). Levels of HB-EGF and AREG mRNAs were estimated by qRT-PCR. Expression values were normalized to those for PBS-treated wild-type mice. Error bars indicate standard deviations (n = 3). (C) Twenty-week-old wild-type mice were intranasally inoculated with PBS or SARS-CoV(MA15) at 10³ PFU/mouse. Mice were injected every day with either PBS or EGFR ligands (AREG plus HB-EGF at 2.5 μg each/mouse/day) beginning on the day of infection until day 9 postinfection. Mice were monitored for weight loss every day. (D) H&E-stained section of 4% PFA-fixed lungs from either PBS- or SARS-CoV(MA15)-inoculated 20-week-old wild-type mice that received either PBS or EGFR ligands at day 9 postinfection (10× magnification). The experiment was performed with n = 5 per group, and images are representative of each group.