tetano
Editor, Senior Moderator
Cell Host Microbe
. 2020 May 27;S1931-3128(20)30302-4.
doi: 10.1016/j.chom.2020.05.020. Online ahead of print.
A Mouse Model of SARS-CoV-2 Infection and Pathogenesis
Shi-Hui Sun[SUP] 1 [/SUP], Qi Chen[SUP] 1 [/SUP], Hong-Jing Gu[SUP] 1 [/SUP], Guan Yang[SUP] 2 [/SUP], Yan-Xiao Wang[SUP] 2 [/SUP], Xing-Yao Huang[SUP] 1 [/SUP], Su-Su Liu[SUP] 3 [/SUP], Na-Na Zhang[SUP] 1 [/SUP], Xiao-Feng Li[SUP] 1 [/SUP], Rui Xiong[SUP] 3 [/SUP], Yan Guo[SUP] 1 [/SUP], Yong-Qiang Deng[SUP] 1 [/SUP], Wei-Jin Huang[SUP] 4 [/SUP], Quan Liu[SUP] 3 [/SUP], Quan-Ming Liu[SUP] 3 [/SUP], Yue-Lei Shen[SUP] 5 [/SUP], Yong Zhou[SUP] 6 [/SUP], Xiao Yang[SUP] 2 [/SUP], Tong-Yan Zhao[SUP] 1 [/SUP], Chang-Fa Fan[SUP] 7 [/SUP], Yu-Sen Zhou[SUP] 8 [/SUP], Cheng-Feng Qin[SUP] 9 [/SUP], You-Chun Wang[SUP] 10 [/SUP]
Affiliations
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.
Keywords: SARS-CoV-2; angiotensin-converting enzyme II; hACE2-KI/NIFDC; mouse model; pathogenesis.
. 2020 May 27;S1931-3128(20)30302-4.
doi: 10.1016/j.chom.2020.05.020. Online ahead of print.
A Mouse Model of SARS-CoV-2 Infection and Pathogenesis
Shi-Hui Sun[SUP] 1 [/SUP], Qi Chen[SUP] 1 [/SUP], Hong-Jing Gu[SUP] 1 [/SUP], Guan Yang[SUP] 2 [/SUP], Yan-Xiao Wang[SUP] 2 [/SUP], Xing-Yao Huang[SUP] 1 [/SUP], Su-Su Liu[SUP] 3 [/SUP], Na-Na Zhang[SUP] 1 [/SUP], Xiao-Feng Li[SUP] 1 [/SUP], Rui Xiong[SUP] 3 [/SUP], Yan Guo[SUP] 1 [/SUP], Yong-Qiang Deng[SUP] 1 [/SUP], Wei-Jin Huang[SUP] 4 [/SUP], Quan Liu[SUP] 3 [/SUP], Quan-Ming Liu[SUP] 3 [/SUP], Yue-Lei Shen[SUP] 5 [/SUP], Yong Zhou[SUP] 6 [/SUP], Xiao Yang[SUP] 2 [/SUP], Tong-Yan Zhao[SUP] 1 [/SUP], Chang-Fa Fan[SUP] 7 [/SUP], Yu-Sen Zhou[SUP] 8 [/SUP], Cheng-Feng Qin[SUP] 9 [/SUP], You-Chun Wang[SUP] 10 [/SUP]
Affiliations
- PMID: 32485164
- DOI: 10.1016/j.chom.2020.05.020
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.
Keywords: SARS-CoV-2; angiotensin-converting enzyme II; hACE2-KI/NIFDC; mouse model; pathogenesis.