The characteristics of hDPP4 transgenic mice subjected to aerosol MERS coronavirus infection via an animal nose-only exposure device

Hao, Xin-yan; Lv, Qi; Li, Feng-di; Xu, Yan-feng; Gao, Hong

After MERS-CoV infection, the disease progression in the mice in the aerosol group was slower than that in the mice in the instillation group. Sanders et al showed that virus droplets were deposited and concentrated in the lungs through the respiratory tract of mice inoculated intranasally, resulting in fast disease onset. 29, 30 Correspondingly, after instillation infection with MERS-CoV, we found that mice with a short airway and high concentration of virus deposited in the lungs displayed weight loss at day 1 and lung lesions at day 3, consistent with intranasal mouse models established by Adam, Agrawal and Li et al [31] [32] [33] ; these mice also exhibited 0% survival by day 5. Previous studies reported that aerosol particles ≤5 μm penetrated the respiratory tract to reach the alveoli and were diffusely distributed in the lungs. 30, 34 In addition, virus aerosols entered the blood circulation through the alveoli, and other viruses slowly replicated in the lungs after mice inhaled MERS-CoV-containing aerosols (particle size: 1.27 ± 0.61 μm). Compared with instillation-inoculated mice with virus deposition in the lungs, aerosol-exposed mice displayed slower disease progression with an incubation period of 5-7 days, lung lesions on day 7, continuous weight loss on days 7-11, milder clinical signs, and 60% survival on day 11.