A mouse model of lethal respiratory dysfunction for SARS-CoV-2 infection.
A mouse model of lethal respiratory dysfunction for SARS-CoV-2 infection.
复制标题
SARS-CoV-2感染致死性呼吸功能障碍的小鼠模型。
DOI：
10.1016/j.antiviral.2021.105138
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发表时间：
2021-09
影响因子：
7.6
通讯作者：
Ooi EE
中科院分区：
文献类型：
--
作者：
Gan ES;Syenina A;Linster M;Ng B;Zhang SL;Watanabe S;Rajarethinam R;Tan HC;Smith GJ;Ooi EE
SARS-CoV-2的全球传播已使数百万人感染COVID-19，甚至更多人因这一大流行病的经济影响而患病。我们对测试新疗法和疫苗的追求需要复制COVID-19病例中所见疾病表型的小动物模型。迄今为止，SARS-CoV-2感染的啮齿动物模型显示出轻度至中度的肺部疾病;死亡率（如果有的话）与中枢神经系统（CNS）感染和功能障碍的显著体征相关。在这里，我们描述了分离的SARS-CoV-2变异与肺部或中枢神经系统感染的倾向。使用从COVID-19患者中分离的野生型SARS-CoV-2，我们首次发现感染在表达人血管紧张素I转化酶2（hACE 2）的转基因小鼠中是致命的。幸运的是，从这些动物的大脑和肺中提取的SARS-CoV-2的全基因组测序显示出遗传差异。同样，从这些人的脑和肺中分离的SARS-CoV-2也显示出斑块形态的差异。将这些脑和肺SARS-CoV-2分离株鼻内接种到新一批hACE 2小鼠中，分别导致致死性CNS和肺部感染。总的来说，我们的研究表明，SARS-CoV-2的遗传变异体可用于复制COVID-19的特定特征，以测试潜在的疫苗或治疗方法。
The global spread of SARS-CoV-2 has made millions ill with COVID-19 and even more from the economic fallout of this pandemic. Our quest to test new therapeutics and vaccines require small animal models that replicate disease phenotypes seen in COVID-19 cases. Rodent models of SARS-CoV-2 infection thus far have shown mild to moderate pulmonary disease; mortality, if any, has been associated with prominent signs of central nervous system (CNS) infection and dysfunction. Here we describe the isolation of SARS-CoV-2 variants with propensity for either pulmonary or CNS infection. Using a wild-type SARS-CoV-2 isolated from a COVID-19 patient, we first found that infection was lethal in transgenic mice expressing the human angiotensin I-converting enzyme 2 (hACE2). Fortuitously, full genome sequencing of SARS-CoV-2 from the brain and lung of these animals showed genetic differences. Likewise, SARS-CoV-2 isolates from brains and lungs of these also showed differences in plaque morphology. Inoculation of these brain and lung SARS-CoV-2 isolates into new batch of hACE2 mice intra-nasally resulted in lethal CNS and pulmonary infection, respectively. Collectively, our study suggests that genetic variants of SARS-CoV-2 could be used to replicate specific features of COVID-19 for the testing of potential vaccines or therapeutics.
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DOI：
10.1126/science.abd3072
发表时间：
2020-11-13
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Daly JL;Simonetti B;Klein K;Chen KE;Williamson MK;Antón-Plágaro C;Shoemark DK;Simón-Gracia L;Bauer M;Hollandi R;Greber UF;Horvath P;Sessions RB;Helenius A;Hiscox JA;Teesalu T;Matthews DA;Davidson AD;Collins BM;Cullen PJ;Yamauchi Y
通讯作者：
Yamauchi Y
影响因子：
6.7
作者：
Yinda CK;Port JR;Bushmaker T;Offei Owusu I;Purushotham JN;Avanzato VA;Fischer RJ;Schulz JE;Holbrook MG;Hebner MJ;Rosenke R;Thomas T;Marzi A;Best SM;de Wit E;Shaia C;van Doremalen N;Munster VJ
通讯作者：
Munster VJ
影响因子：
11.1
作者：
Wang, Chaofu;Xie, Jing;Bian, Xiu-Wu
通讯作者：
Bian, Xiu-Wu
影响因子：
6.4
作者：
Su, Yvonne C. F.;Anderson, Danielle E.;Smith, Gavin J. D.
通讯作者：
Smith, Gavin J. D.
影响因子：
5.4
作者：
McCray, Paul B., Jr.;Pewe, Lecia;Perlman, Stanley
通讯作者：
Perlman, Stanley