A Mouse Model of SARS-CoV-2 Infection and Pathogenesis
A Mouse Model of SARS-CoV-2 Infection and Pathogenesis
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SARS-CoV-2 感染和发病机制的小鼠模型
DOI：
10.1016/j.chom.2020.05.020
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发表时间：
2020-07-08
影响因子：
30.3
通讯作者：
Wang, You-Chun
中科院分区：
文献类型：
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作者：
Sun, Shi-Hui;Chen, Qi;Wang, You-Chun
2019年12月以来，新型冠状病毒SARS-CoV-2出现并在全球迅速传播，引发全球突发公共卫生事件。疫苗和抗病毒药物的缺乏带来了对动物模型的迫切需求。人血管紧张素转换酶II(ACE2)是SARS-CoV-2的功能性受体。在本研究中，我们利用CRISPR/Cas9敲打技术建立了表达人血管紧张素转换酶2(HACE2)的小鼠模型。与野生型C57BL/6小鼠相比，年轻和老年hACE2小鼠在鼻腔感染时，肺、气管和脑中的病毒载量都很高。虽然没有观察到死亡，但在感染SARS-CoV-2的老年hACE2小鼠中，观察到间质性肺炎和细胞因子升高。有趣的是，胃内接种SARS-CoV-2可以引起hACE2小鼠的生殖性感染和肺部病变。总体而言，本文描述的这个动物模型为研究SARS-CoV-2的传播和发病机制以及评估新冠肺炎疫苗和治疗方法提供了一个有用的工具。
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.