Pathogenesis of SARS-CoV-2 in Transgenic Mice Expressing Human Angiotensin-Converting Enzyme 2

被引:430
作者
Jiang, Ren-Di [1 ,2 ]
Liu, Mei-Qin [1 ,2 ]
Chen, Ying [1 ,2 ]
Shan, Chao [1 ]
Zhou, Yi-Wu [3 ]
Shen, Xu-Rui [1 ,2 ]
Li, Qian [1 ,2 ]
Zhang, Lei [1 ]
Zhu, Yan [1 ]
Si, Hao-Rui [1 ,2 ]
Wang, Qi [1 ]
Min, Juan [1 ]
Wang, Xi [1 ,2 ]
Zhang, Wei [1 ]
Li, Bei [1 ]
Zhang, Hua-Jun [1 ]
Baric, Ralph S. [4 ]
Zhou, Peng [1 ]
Yang, Xing-Lou [1 ]
Shi, Zheng-Li [1 ]
机构
[1] Chinese Acad Sci, Ctr Biosafety Megasci, Wuhan Inst Virol, CAS Key Lab Special Pathogens, Wuhan, Hubei, Peoples R China
[2] Univ Chinese Acad Sci, Beijing, Peoples R China
[3] Huazhong Univ Sci & Technol, Dept Forens Med, Tongji Med Coll, Wuhan, Hubei, Peoples R China
[4] Univ North Carolina, Chapel Hill, NC 27515 USA
关键词
RESPIRATORY SYNDROME CORONAVIRUS; CLINICAL CHARACTERISTICS; INFECTION; SARS; MODELS;
D O I
10.1016/j.cell.2020.05.027
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
COVID-19 has spread worldwide since 2019 and is now a severe threat to public health. We previously identified the causative agent as a novel SARS-related coronavirus (SARS-CoV-2) that uses human angiotensin-converting enzyme 2 (hACE2) as the entry receptor. Here, we successfully developed a SARS-CoV-2 hACE2 transgenic mouse (HFH4-hACE2 in C3B6 mice) infection model. The infected mice generated typical interstitial pneumonia and pathology that were similar to those of COVID-19 patients. Viral quantification revealed the lungs as the major site of infection, although viral RNA could also be found in the eye, heart, and brain in some mice. Virus identical to SARS-CoV-2 in full-genome sequences was isolated from the infected lung and brain tissues. Last, we showed that pre-exposure to SARS-CoV-2 could protect mice from severe pneumonia. Our results show that the hACE2 mouse would be a valuable tool for testing potential vaccines and therapeutics.
引用
收藏
页码:50 / +
页数:17
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