A Mouse Model of SARS-CoV-2 Infection and Pathogenesis.

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.

• Authors: Shi-Hui Sun, Qi Chen, Hong-Jing Gu, Guan Yang, Yan-Xiao Wang, Xing-Yao Huang, Su-Su Liu, Na-Na Zhang, Xiao-Feng Li, Rui Xiong, Yan Guo, Yong-Qiang Deng, Wei-Jin Huang, Quan Liu, Quan-Ming Liu, Yue-Lei Shen, Yong Zhou, Xiao Yang, Tong-Yan Zhao, Chang-Fa Fan, Yu-Sen Zhou, Cheng-Feng Qin, You-Chun Wang
• Journal: Cell host & microbe (Cell Host Microbe) Vol. 28 Issue 1 Pg. 124-133.e4 (07 08 2020) ISSN: 1934-6069 [Electronic] United States
• PMID: 32485164 (Publication Type: Journal Article)
• Copyright: Copyright © 2020 Elsevier Inc. All rights reserved.

Chemical References

• Cytokines
• RNA, Viral
• Peptidyl-Dipeptidase A
• ACE2 protein, human
• Ace2 protein, mouse
• Angiotensin-Converting Enzyme 2

Topics

• Aging
• Angiotensin-Converting Enzyme 2
• Animals
• Betacoronavirus (physiology)
• Brain (virology)
• COVID-19
• CRISPR-Cas Systems
• Coronavirus Infections (pathology, virology)
• Cytokines (blood)
• Disease Models, Animal
• Gene Knock-In Techniques
• Lung (pathology, virology)
• Lung Diseases, Interstitial (pathology)
• Mice, Inbred C57BL
• Nose (virology)
• Pandemics
• Peptidyl-Dipeptidase A (genetics, metabolism)
• Pneumonia, Viral (pathology, virology)
• RNA, Viral (analysis)
• SARS-CoV-2
• Stomach (virology)
• Trachea (virology)
• Viral Load
• Virus Replication