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A Mouse Model of SARS-CoV-2 Infection and Pathogenesis.
Sun, Shi-Hui; Chen, Qi; Gu, Hong-Jing; Yang, Guan; Wang, Yan-Xiao; Huang, Xing-Yao; Liu, Su-Su; Zhang, Na-Na; Li, Xiao-Feng; Xiong, Rui; Guo, Yan; Deng, Yong-Qiang; Huang, Wei-Jin; Liu, Quan; Liu, Quan-Ming; Shen, Yue-Lei; Zhou, Yong; Yang, Xiao; Zhao, Tong-Yan; Fan, Chang-Fa; Zhou, Yu-Sen; Qin, Cheng-Feng; Wang, You-Chun.
  • Sun SH; State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Academy of Military Medical Sciences (AMMS), Beijing 100071, China.
  • Chen Q; State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Academy of Military Medical Sciences (AMMS), Beijing 100071, China.
  • Gu HJ; State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Academy of Military Medical Sciences (AMMS), Beijing 100071, China.
  • Yang G; State Key Laboratory of Proteomics, Beijing Proteome Research Center, National Center for Protein Science(Beijing), Beijing Institute of Lifeomics, Beijing 102206, China.
  • Wang YX; State Key Laboratory of Proteomics, Beijing Proteome Research Center, National Center for Protein Science(Beijing), Beijing Institute of Lifeomics, Beijing 102206, China.
  • Huang XY; State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Academy of Military Medical Sciences (AMMS), Beijing 100071, China.
  • Liu SS; Division of Animal Model Research, Institute for Laboratory Animal Resources, National Institutes for Food and Drug Control, Beijing 102629, China.
  • Zhang NN; State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Academy of Military Medical Sciences (AMMS), Beijing 100071, China.
  • Li XF; State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Academy of Military Medical Sciences (AMMS), Beijing 100071, China.
  • Xiong R; Division of Animal Model Research, Institute for Laboratory Animal Resources, National Institutes for Food and Drug Control, Beijing 102629, China.
  • Guo Y; State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Academy of Military Medical Sciences (AMMS), Beijing 100071, China.
  • Deng YQ; State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Academy of Military Medical Sciences (AMMS), Beijing 100071, China.
  • Huang WJ; Division of HIV/AIDS and Sex-Transmitted Virus Vaccines, Institute for Biological Product Control, National Institutes for Food and Drug Control (NIFDC), Beijing 102629, China.
  • Liu Q; Division of Animal Model Research, Institute for Laboratory Animal Resources, National Institutes for Food and Drug Control, Beijing 102629, China.
  • Liu QM; Division of Animal Model Research, Institute for Laboratory Animal Resources, National Institutes for Food and Drug Control, Beijing 102629, China.
  • Shen YL; Beijing Biocytogen Co., Ltd., Beijing 101111, China.
  • Zhou Y; Chongqing Weisiteng Biotech Transnational Research Institute, Chongqing 400039, China.
  • Yang X; State Key Laboratory of Proteomics, Beijing Proteome Research Center, National Center for Protein Science(Beijing), Beijing Institute of Lifeomics, Beijing 102206, China.
  • Zhao TY; State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Academy of Military Medical Sciences (AMMS), Beijing 100071, China.
  • Fan CF; Division of Animal Model Research, Institute for Laboratory Animal Resources, National Institutes for Food and Drug Control, Beijing 102629, China.. Electronic address: fancf@nifdc.org.cn.
  • Zhou YS; State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Academy of Military Medical Sciences (AMMS), Beijing 100071, China. Electronic address: yszhou@bmi.ac.cn.
  • Qin CF; State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Academy of Military Medical Sciences (AMMS), Beijing 100071, China. Electronic address: qincf@bmi.ac.cn.
  • Wang YC; Division of HIV/AIDS and Sex-Transmitted Virus Vaccines, Institute for Biological Product Control, National Institutes for Food and Drug Control (NIFDC), Beijing 102629, China. Electronic address: wangyc@nifdc.org.cn.
Cell Host Microbe ; 28(1): 124-133.e4, 2020 07 08.
Article in English | MEDLINE | ID: covidwho-378130
Semantic information from SemMedBD (by NLM)
1. dipeptidyl peptidase II PART_OF Homo sapiens
Subject
dipeptidyl peptidase II
Predicate
PART_OF
Object
Homo sapiens
2. ACE2 gene|ACE2 PART_OF Homo sapiens
Subject
ACE2 gene|ACE2
Predicate
PART_OF
Object
Homo sapiens
3. Pneumoni COEXISTS_WITH C5203676
Subject
Pneumoni
Predicate
COEXISTS_WITH
Object
C5203676
4. 2019 novel coronavirus CAUSES Pulmonary Pathology
Subject
2019 novel coronavirus
Predicate
CAUSES
Object
Pulmonary Pathology
5. Pulmonary Pathology PROCESS_OF Mus
Subject
Pulmonary Pathology
Predicate
PROCESS_OF
Object
Mus
6. dipeptidyl peptidase II PART_OF Homo sapiens
Subject
dipeptidyl peptidase II
Predicate
PART_OF
Object
Homo sapiens
7. ACE2 gene|ACE2 PART_OF Homo sapiens
Subject
ACE2 gene|ACE2
Predicate
PART_OF
Object
Homo sapiens
8. Pneumonia, Interstitial COEXISTS_WITH 2019 novel coronavirus
Subject
Pneumonia, Interstitial
Predicate
COEXISTS_WITH
Object
2019 novel coronavirus
9. 2019 novel coronavirus CAUSES Pulmonary Pathology
Subject
2019 novel coronavirus
Predicate
CAUSES
Object
Pulmonary Pathology
10. Pulmonary Pathology PROCESS_OF Mus
Subject
Pulmonary Pathology
Predicate
PROCESS_OF
Object
Mus
ABSTRACT
Since December 2019, a novel coronavirus SARS-CoV-2 has emerged and rapidly spread throughout the world, resulting in a global public health emergency. The lack of vaccine and antivirals has brought an urgent need for an animal model. Human angiotensin-converting enzyme II (ACE2) has been identified as a functional receptor for SARS-CoV-2. In this study, we generated a mouse model expressing human ACE2 (hACE2) by using CRISPR/Cas9 knockin technology. In comparison with wild-type C57BL/6 mice, both young and aged hACE2 mice sustained high viral loads in lung, trachea, and brain upon intranasal infection. Although fatalities were not observed, interstitial pneumonia and elevated cytokines were seen in SARS-CoV-2 infected-aged hACE2 mice. Interestingly, intragastric inoculation of SARS-CoV-2 was seen to cause productive infection and lead to pulmonary pathological changes in hACE2 mice. Overall, this animal model described here provides a useful tool for studying SARS-CoV-2 transmission and pathogenesis and evaluating COVID-19 vaccines and therapeutics.
Subject(s)
Keywords

Full text: Available Collection: International databases Database: MEDLINE Main subject: Pneumonia, Viral / Coronavirus Infections / Disease Models, Animal / Pandemics / Betacoronavirus / Mice, Inbred C57BL Type of study: Etiology study Topics: Vaccines Limits: Animals Language: English Journal: Cell Host Microbe Journal subject: Microbiology Year: 2020 Document Type: Article Affiliation country: J.chom.2020.05.020

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Pneumonia, Viral / Coronavirus Infections / Disease Models, Animal / Pandemics / Betacoronavirus / Mice, Inbred C57BL Type of study: Etiology study Topics: Vaccines Limits: Animals Language: English Journal: Cell Host Microbe Journal subject: Microbiology Year: 2020 Document Type: Article Affiliation country: J.chom.2020.05.020