DOI: 10.1002/ame2.12088
The characteristics of hDPP4 transgenic mice subjected to aerosol MERS coronavirus infection via an animal nose-only exposure device
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, Beijing, China
摘要：Background: Middle East respiratory syndrome coronavirus (MERS-CoV), 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 health. Methods: To simulate the clinical aerosol transmission route, hDPP4 transgenic mice were infected with MERS-CoV by an animal nose-only exposure device and com-pared 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, histopa-thology, viral antigen distribution, and cytokines in tissues. Results: MERS-CoV 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-CoV instil-lation-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-CoV aerosol-in-fected mice than in the MERS-CoV instillation-inoculated mice. Conclusion: hDPP4 transgenic mice were successfully infected with MERS-CoV aer-osols 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-CoV developed disease and lung pathology progressions that more closely resembled those observed in humans.
机标关键词：transgenic miceproinflammatory cytokinesweight lossinterstitial pneumoniaviral replicationclinical signspublic healthviral load
论文发表日期：2019-01-01
在线出版日期：2025-08-15（本平台首次上网日期，不代表文献的发表时间）
页数：13( 269-281 )
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