PMID- 32516571 OWN - NLM STAT- MEDLINE DCOM- 20200716 LR - 20240329 IS - 1097-4172 (Electronic) IS - 0092-8674 (Print) IS - 0092-8674 (Linking) VI - 182 IP - 1 DP - 2020 Jul 9 TI - Pathogenesis of SARS-CoV-2 in Transgenic Mice Expressing Human Angiotensin-Converting Enzyme 2. PG - 50-58.e8 LID - S0092-8674(20)30622-X [pii] LID - 10.1016/j.cell.2020.05.027 [doi] AB - 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. CI - Copyright (c) 2020 Elsevier Inc. All rights reserved. FAU - Jiang, Ren-Di AU - Jiang RD AD - CAS Key Laboratory of Special Pathogens, Wuhan Institute of Virology, Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan, Hubei, People's Republic of China; University of Chinese Academy of Sciences, Beijing, People's Republic of China. FAU - Liu, Mei-Qin AU - Liu MQ AD - CAS Key Laboratory of Special Pathogens, Wuhan Institute of Virology, Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan, Hubei, People's Republic of China; University of Chinese Academy of Sciences, Beijing, People's Republic of China. FAU - Chen, Ying AU - Chen Y AD - CAS Key Laboratory of Special Pathogens, Wuhan Institute of Virology, Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan, Hubei, People's Republic of China; University of Chinese Academy of Sciences, Beijing, People's Republic of China. FAU - Shan, Chao AU - Shan C AD - CAS Key Laboratory of Special Pathogens, Wuhan Institute of Virology, Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan, Hubei, People's Republic of China. FAU - Zhou, Yi-Wu AU - Zhou YW AD - Department of Forensic Medicine, Tongji Medical College of Huazhong University of Science and Technology, Wuhan, Hubei, People's Republic of China. FAU - Shen, Xu-Rui AU - Shen XR AD - CAS Key Laboratory of Special Pathogens, Wuhan Institute of Virology, Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan, Hubei, People's Republic of China; University of Chinese Academy of Sciences, Beijing, People's Republic of China. FAU - Li, Qian AU - Li Q AD - CAS Key Laboratory of Special Pathogens, Wuhan Institute of Virology, Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan, Hubei, People's Republic of China; University of Chinese Academy of Sciences, Beijing, People's Republic of China. FAU - Zhang, Lei AU - Zhang L AD - CAS Key Laboratory of Special Pathogens, Wuhan Institute of Virology, Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan, Hubei, People's Republic of China. FAU - Zhu, Yan AU - Zhu Y AD - CAS Key Laboratory of Special Pathogens, Wuhan Institute of Virology, Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan, Hubei, People's Republic of China. FAU - Si, Hao-Rui AU - Si HR AD - CAS Key Laboratory of Special Pathogens, Wuhan Institute of Virology, Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan, Hubei, People's Republic of China; University of Chinese Academy of Sciences, Beijing, People's Republic of China. FAU - Wang, Qi AU - Wang Q AD - CAS Key Laboratory of Special Pathogens, Wuhan Institute of Virology, Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan, Hubei, People's Republic of China. FAU - Min, Juan AU - Min J AD - CAS Key Laboratory of Special Pathogens, Wuhan Institute of Virology, Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan, Hubei, People's Republic of China. FAU - Wang, Xi AU - Wang X AD - CAS Key Laboratory of Special Pathogens, Wuhan Institute of Virology, Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan, Hubei, People's Republic of China; University of Chinese Academy of Sciences, Beijing, People's Republic of China. FAU - Zhang, Wei AU - Zhang W AD - CAS Key Laboratory of Special Pathogens, Wuhan Institute of Virology, Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan, Hubei, People's Republic of China. FAU - Li, Bei AU - Li B AD - CAS Key Laboratory of Special Pathogens, Wuhan Institute of Virology, Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan, Hubei, People's Republic of China. FAU - Zhang, Hua-Jun AU - Zhang HJ AD - CAS Key Laboratory of Special Pathogens, Wuhan Institute of Virology, Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan, Hubei, People's Republic of China. FAU - Baric, Ralph S AU - Baric RS AD - University of North Carolina at Chapel Hill, Chapel Hill, NC, USA. FAU - Zhou, Peng AU - Zhou P AD - CAS Key Laboratory of Special Pathogens, Wuhan Institute of Virology, Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan, Hubei, People's Republic of China. FAU - Yang, Xing-Lou AU - Yang XL AD - CAS Key Laboratory of Special Pathogens, Wuhan Institute of Virology, Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan, Hubei, People's Republic of China. Electronic address: yangxl@wh.iov.cn. FAU - Shi, Zheng-Li AU - Shi ZL AD - CAS Key Laboratory of Special Pathogens, Wuhan Institute of Virology, Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan, Hubei, People's Republic of China. Electronic address: zlshi@wh.iov.cn. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20200521 PL - United States TA - Cell JT - Cell JID - 0413066 RN - EC 3.4.15.1 (Peptidyl-Dipeptidase A) RN - EC 3.4.17.23 (ACE2 protein, human) RN - EC 3.4.17.23 (Ace2 protein, mouse) RN - EC 3.4.17.23 (Angiotensin-Converting Enzyme 2) SB - IM MH - Angiotensin-Converting Enzyme 2 MH - Animals MH - Betacoronavirus/*physiology MH - COVID-19 MH - Coronavirus Infections/*pathology MH - *Disease Models, Animal MH - Female MH - Humans MH - Lung Diseases, Interstitial/pathology/virology MH - Male MH - Mice MH - Mice, Inbred C3H MH - Mice, Inbred C57BL MH - *Mice, Transgenic/genetics MH - Pandemics MH - Peptidyl-Dipeptidase A/genetics MH - Pneumonia, Viral/*pathology MH - SARS-CoV-2 MH - Viral Tropism MH - Weight Loss PMC - PMC7241398 OTO - NOTNLM OT - COVID-19 OT - SARS-CoV-2 OT - human ACE2 transgenic mouse OT - pneumonia COIS- Declaration of Interests The authors declare no competing interests. EDAT- 2020/06/10 06:00 MHDA- 2020/07/17 06:00 PMCR- 2020/05/21 CRDT- 2020/06/10 06:00 PHST- 2020/03/12 00:00 [received] PHST- 2020/04/27 00:00 [revised] PHST- 2020/05/14 00:00 [accepted] PHST- 2020/06/10 06:00 [pubmed] PHST- 2020/07/17 06:00 [medline] PHST- 2020/06/10 06:00 [entrez] PHST- 2020/05/21 00:00 [pmc-release] AID - S0092-8674(20)30622-X [pii] AID - 10.1016/j.cell.2020.05.027 [doi] PST - ppublish SO - Cell. 2020 Jul 9;182(1):50-58.e8. doi: 10.1016/j.cell.2020.05.027. Epub 2020 May 21.