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The characteristics of hdpp4 transgenic mice subjected to aerosol MERS coronavirus infection via an animal nose-only exposure device

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Animal Models and Experimental Medicine 2019年第4期2卷 269-281页

作者： Xin-yan Hao Qi Lv Feng-di Li Yan-feng Xu Hong Gao Institute of Laboratory Animal Sciences Chinese Academy of Medical Sciences(CAMS)& Comparative Medicine Centre Peking Union Medical College(PUMC) Key Laboratory of Human Disease Comparative Medicine National Health Commission of China(NHC) Beijing Key Laboratory for Animal Models of Emerging and Reemerging Infections

Background: Middle East respiratory syndrome coronavirus(MERS-Co V), which is not fully understood in regard to certain transmission routes and pathogenesis and lacks specific therapeutics and vaccines, poses a global threat to public ***: To simulate the clinical aerosol transmission route, h DPP4 transgenic mice were infected with MERS-Co V by an animal nose-only exposure device and compared with instillation-inoculated mice. The challenged mice were observed for 14 consecutive days and necropsied on days 3, 5, 7, and 9 to analyze viral load, histopathology, viral antigen distribution, and cytokines in ***: MERS-Co V aerosol-infected mice with an incubation period of 5-7 days showed weight loss on days 7-11, obvious lung lesions on day 7, high viral loads in the lungs on days 3-9 and in the brain on days 7-9, and 60% survival. MERS-Co V instillation-inoculated mice exhibited clinical signs on day 1, obvious lung lesions on days 3-5, continuous weight loss, 0% survival by day 5, and high viral loads in the lungs and brain on days 3-5. Viral antigen and high levels of proinflammatory cytokines and chemokines were detected in the aerosol and instillation groups. Disease, lung lesion, and viral replication progressions were slower in the MERS-Co V aerosol-infected mice than in the MERS-Co V instillation-inoculated ***: h DPP4 transgenic mice were successfully infected with MERS-Co V aerosols via an animal nose-only exposure device, and aerosol-and instillation-infected mice simulated the clinical symptoms of moderate diffuse interstitial pneumonia. However, the transgenic mice exposed to aerosol MERS-Co V developed disease and lung pathology progressions that more closely resembled those observed in humans.

关键词： animal nose‐only exposure device hdpp4 transgenic mice intranasal instillation MERS‐CoVaerosol infection

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