The pathogenicity of SARS-CoV-2 in hACE2 transgenic mice

被引：808

作者：

Bao, Linlin ^{[1
,2
]}

Deng, Wei ^{[1
,2
]}

Huang, Baoying ^{[3
]}

Gao, Hong ^{[1
,2
]}

Liu, Jiangning ^{[1
,2
]}

Ren, Lili

Wei, Qiang ^{[1
,2
]}

Yu, Pin ^{[1
,2
]}

Xu, Yanfeng ^{[1
,2
]}

Qi, Feifei ^{[1
,2
]}

Qu, Yajin ^{[1
,2
]}

Li, Fengdi ^{[1
,2
]}

Lv, Qi ^{[1
,2
]}

Wang, Wenling ^{[3
]}

Xue, Jing ^{[1
,2
]}

Gong, Shuran ^{[1
,2
]}

Liu, Mingya ^{[1
,2
]}

Wang, Guanpeng ^{[1
,2
]}

Wang, Shunyi ^{[1
,2
]}

Song, Zhiqi ^{[1
,2
]}

Zhao, Linna ^{[1
,2
]}

Liu, Peipei ^{[3
]}

Zhao, Li ^{[3
]}

Ye, Fei ^{[3
]}

Wang, Huijuan ^{[3
]}

Zhou, Weimin ^{[3
]}

Zhu, Na ^{[3
]}

Zhen, Wei ^{[3
]}

Yu, Haisheng ^{[1
,2
]}

Zhang, Xiaojuan ^{[1
,2
]}

Guo, Li ^{[4
]}

Chen, Lan ^{[4
]}

Wang, Conghui ^{[4
]}

Wang, Ying ^{[4
]}

Wang, Xinming ^{[4
]}

Xiao, Yan ^{[4
]}

Sun, Qiangming ^{[5
]}

Liu, Hongqi ^{[5
]}

Zhu, Fanli ^{[5
]}

Ma, Chunxia ^{[5
]}

Yan, Lingmei ^{[5
]}

Yang, Mengli ^{[5
]}

Han, Jun ^{[3
]}

Xu, Wenbo ^{[3
]}

Tan, Wenjie ^{[3
]}

Peng, Xiaozhong ^{[5
]}

Jin, Qi ^{[4
]}

Wu, Guizhen ^{[3
]}

Qin, Chuan ^{[1
,2
]}

机构：

[1] Chinese Acad Med Sci, Beijing Key Lab Anim Models Emerging & Remerging, Inst Lab Anim Sci, Beijing, Peoples R China

[2] Peking Union Med Coll, Comparat Med Ctr, NHC Key Lab Human Dis Comparat Med, Beijing, Peoples R China

[3] China CDC, Natl Inst Viral Dis Control & Prevent, MHC Key Lab Biosafety, Beijing, Peoples R China

[4] Chinese Acad Med Sci, Inst Pathogen Biol, Beijing, Peoples R China

[5] Chinese Acad Med Sci, Inst Med Biol, Beijing, Peoples R China

来源：

NATURE | 2020年 / 583卷 / 7818期

关键词：

CORONAVIRUS; SARS;

D O I：

10.1038/s41586-020-2312-y

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页码：830 / +

页数：11

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