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Tytuł:
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A Mouse Model of SARS-CoV-2 Infection and Pathogenesis.
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Autorzy:
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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: .
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: .
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: .
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: .
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Źródło:
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Cell host & microbe [Cell Host Microbe] 2020 Jul 08; Vol. 28 (1), pp. 124-133.e4. Date of Electronic Publication: 2020 May 27.
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Typ publikacji:
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Journal Article
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Język:
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English
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Imprint Name(s):
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Original Publication: Cambridge, Mass. : Cell Press
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MeSH Terms:
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Coronavirus Infections*/pathology
Coronavirus Infections*/virology
Disease Models, Animal*
Mice, Inbred C57BL*
Pandemics*
Pneumonia, Viral*/pathology
Pneumonia, Viral*/virology
Betacoronavirus/*physiology
Aging ; Angiotensin-Converting Enzyme 2 ; Animals ; Brain/virology ; COVID-19 ; CRISPR-Cas Systems ; Cytokines/blood ; Gene Knock-In Techniques ; Lung/pathology ; Lung/virology ; Lung Diseases, Interstitial/pathology ; Nose/virology ; Peptidyl-Dipeptidase A/genetics ; Peptidyl-Dipeptidase A/metabolism ; RNA, Viral/analysis ; SARS-CoV-2 ; Stomach/virology ; Trachea/virology ; Viral Load ; Virus Replication
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Contributed Indexing:
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Keywords: SARS-CoV-2; angiotensin-converting enzyme II; hACE2-KI/NIFDC; mouse model; pathogenesis
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Substance Nomenclature:
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0 (Cytokines)
0 (RNA, Viral)
EC 3.4.15.1 (Peptidyl-Dipeptidase A)
EC 3.4.17.23 (ACE2 protein, human)
EC 3.4.17.23 (Ace2 protein, mouse)
EC 3.4.17.23 (Angiotensin-Converting Enzyme 2)
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Entry Date(s):
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Date Created: 20200603 Date Completed: 20200717 Latest Revision: 20210110
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Update Code:
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20240104
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PubMed Central ID:
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PMC7250783
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DOI:
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10.1016/j.chom.2020.05.020
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PMID:
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32485164
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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.
Competing Interests: Declaration of Interests The authors declare no competing interests.
(Copyright © 2020 Elsevier Inc. All rights reserved.)
