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

作     者：Xin-yan Hao Qi Lv Feng-di Li Yan-feng Xu Hong Gao 

作者机构：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 

出 版 物：《Animal Models and Experimental Medicine》 (动物模型与实验医学（英文）)

年 卷 期：2019年第2卷第4期

页      面：269-281页

核心收录：

学科分类：1004[医学-公共卫生与预防医学(可授医学、理学学位)] 100401[医学-流行病与卫生统计学] 10[医学] 

基　　金：National Science and Technology Major Projects of Infectious Disease  Grant/Award Number: 2018ZX10734401-011 

主　　题：animal nose‐only exposure device hDPP4 transgenic mice intranasal instillation MERS‐CoVaerosol infection 

摘      要：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.