Figure 1.

MERS-CoV infection in hDPP4-Tg mice causes mortality and morbidity with progressive pulmonary fibrosis. hDPP4-Tg mice and transgene-negative littermates were challenged intranasally with MERS-CoV (10⁴ or 10⁵ plaque-forming unit (PFU)) or phosphate-buffered saline (PBS). Infected mice were monitored every other day for weight loss, clinical symptoms, and survival. (A) Survival of hDPP4-Tg mice (TG) and transgene-negative littermates (WT) after infection with MERS-CoV or sham (PBS, control) (n = 10). (B) Histopathological changes in the lungs of hDPP4-Tg mice and transgene-negative littermates (WT) challenged with MERS-CoV or PBS (sham-infected). Ten days after MERS-CoV or sham infection, lung tissues were collected, fixed, and paraffin-embedded for hematoxylin and eosin staining. Hematoxylin and eosin (H&E)-stained lung sections were analyzed for inflammation by light microscopy. Transgene-negative littermates (WT) and sham-infected hDPP4-Tg mice represented normal lung tissue with thin-lined alveolar septa and well-architected alveoli. Virus-challenged groups showed distorted lung morphologies, including collapsed alveolar spaces with wider and thicker alveolar septa and perivascular and peribronchial cuffing. Regions of inflammatory cell infiltration around vasculature, bronchiole, and proximal alveoli were noted by arrowheads. Scale bars = 100 µm. (C) Effects of MERS-CoV infection in the expression of ER-stress-associated genes in the lungs of hDPP4-Tg mice. Total RNA was extracted from the lungs of hDPP4-Tg mice four and six days after infection with MERS-CoV. Relative expression of ER-stress-associated genes was determined by qRT-PCR after normalizing to β-actin mRNA levels. Reactions were performed in duplicates. Fold changes relative to non-treated controls are shown as means ± SD (n = 2). * p < 0.05 and ** p < 0.01.