FIG 3.
Transgenic mice expressing hCD26 are permissive to MERS-CoV infection, leading to morbidity and mortality. Both hCD26 Tg+ and Tg− mice, nine animals each, were challenged i.n. with 106 TCID50 of MERS-CoV in 80 μl. Infected mice were monitored daily for their weight gain or loss (A), other signs of clinical illness, and mortality (B). Two animals were euthanized at 2 and 4 dpi to determine the viral loads in various tissues harvested by quantifying infectious virus isolated (C) and viral RNA targeting upstream E gene by qRT-PCR (D). In addition, paraffin-embedded lung (E and F) and brain (G and H) tussues were stained for MERS-CoV antigen with a specific anti-MERS-CoV antibody raised in rabbits, as described in Materials and Methods. (A) Persistent weight loss (up to 30%) in infected Tg+, but not Tg−, mice. (B) Cumulative survival rate of infected mice. Tg+ mice succumbed to infection with 100% mortality at 6 dpi. (C) Infectious virus titers, expressed as log10 TCID50 per g of tissue, in the lungs and brain. (D) Copy numbers of viral E gene in the indicated tissues of Tg+ mice, relative to those derived from Tg− littermates. (E and F) Viral antigen (red) was readily detected in alveolar pneumocytes of Tg+ (E), but not Tg− (F), mice at 2 dpi. (G and H) Viral antigen (red) was also detected in neurons (green arrow), microglia (arrowhead), astrocytes (black arrow), and astrocyte processes (star) in the brains of Tg+ (G), but not Tg− (H), mice at 4 dpi.