The pathogenicity of SARS-CoV-2 in hACE2 transgenic mice
The pathogenicity of SARS-CoV-2 in hACE2 transgenic mice
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DOI：
10.1038/s41586-020-2312-y
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发表时间：
2020-05-07
期刊：
影响因子：
64.8
通讯作者：
Qin, Chuan
中科院分区：
文献类型：
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作者：
Bao, Linlin;Deng, Wei;Qin, Chuan
严重急性呼吸综合征冠状病毒2型（SARS-CoV-2）是2019冠状病毒病（COVID-19）的病因，已成为国际关注的突发公共卫生事件(1)。血管紧张素转换酶2 （ACE2）是严重急性呼吸综合征冠状病毒（SARS-CoV）的细胞进入受体(2)。本研究用SARS-CoV-2感染表达人ACE2的转基因小鼠（以下简称hACE2小鼠），并研究该病毒的致病性。我们观察到感染SARS-CoV-2的hACE2小鼠的体重减轻以及肺部的病毒复制。典型的组织病理为间质性肺炎，大量巨噬细胞和淋巴细胞浸润肺泡间质，巨噬细胞在肺泡腔内积聚。我们在支气管上皮细胞、巨噬细胞和肺泡上皮细胞中观察到病毒抗原。这些现象在感染SARS-CoV-2的野生型小鼠中未发现。值得注意的是，我们已经证实了SARS-CoV-2对hACE2小鼠的致病性。该小鼠SARS-CoV-2感染模型对于评估抗病毒药物和疫苗以及了解COVID-19的发病机制具有重要价值。感染SARS-CoV-2可在表达人类版ACE2的转基因小鼠的肺部引起间质性肺炎和病毒复制，从而在该模型中证实了该病毒的致病性。
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of coronavirus disease 2019 (COVID-19), which has become a public health emergency of international concern(1). Angiotensin-converting enzyme 2 (ACE2) is the cell-entry receptor for severe acute respiratory syndrome coronavirus (SARS-CoV)(2). Here we infected transgenic mice that express human ACE2 (hereafter, hACE2 mice) with SARS-CoV-2 and studied the pathogenicity of the virus. We observed weight loss as well as virus replication in the lungs of hACE2 mice infected with SARS-CoV-2. The typical histopathology was interstitial pneumonia with infiltration of considerable numbers of macrophages and lymphocytes into the alveolar interstitium, and the accumulation of macrophages in alveolar cavities. We observed viral antigens in bronchial epithelial cells, macrophages and alveolar epithelia. These phenomena were not found in wild-type mice infected with SARS-CoV-2. Notably, we have confirmed the pathogenicity of SARS-CoV-2 in hACE2 mice. This mouse model of SARS-CoV-2 infection will be valuable for evaluating antiviral therapeutic agents and vaccines, as well as understanding the pathogenesis of COVID-19.Infection with SARS-CoV-2 causes interstitial pneumonia and viral replication in the lungs of transgenic mice that express a human version of ACE2, confirming the pathogenicity of the virus in this model.