人類ACE2轉基因小鼠的SARS-CoV-2感染可導致嚴重的肺部炎症

人類ACE2轉基因小鼠的SARS-CoV-2感染可導致嚴重的肺部炎症

作者：

小柯機器人

發布時間：2020/8/26 14:01:45

美國華盛頓大學醫學院Michael S. Diamond課題組發現，人類ACE2轉基因小鼠的SARS-CoV-2感染可導致嚴重的肺部炎症和功能受損。該項研究成果於2020年8月24日在線發表在《自然—免疫學》雜誌上。

研究人員評估了表達由細胞角蛋白18（K18）基因啟動子驅動的人血管緊張素I轉換酶2（ACE2）受體（K18-hACE2）的轉基因小鼠，其可作為SARS-CoV-2感染的模型。在K18-hACE2小鼠中鼻內接種SARS-CoV-2會導致肺部高水平的病毒感染，並傳播到其他器官。病毒滴度達到峰值後4天，肺功能下降，並與單核細胞、嗜中性粒細胞和活化的T細胞浸潤有關。SARS-CoV-2感染的肺組織顯示出大量上調的先天免疫反應，並帶有核因子-κB依賴性、I型和II型幹擾素信號傳導以及白細胞激活途徑。

 

因此，SARS-CoV-2感染的K18-hACE2模型具有嚴重COVID-19感染的許多特徵，可用於定義肺部疾病的基礎並測試基於免疫和抗病毒的對策。

 

據介紹，儘管已經對動物模型進行了SARS-CoV-2感染的評估，但沒有一個動物模型能夠完全概括住院患者的肺部疾病表型。

 

附：英文原文

Title: SARS-CoV-2 infection of human ACE2-transgenic mice causes severe lung inflammation and impaired function

Author: Emma S. Winkler, Adam L. Bailey, Natasha M. Kafai, Sharmila Nair, Broc T. McCune, Jinsheng Yu, Julie M. Fox, Rita E. Chen, James T. Earnest, Shamus P. Keeler, Jon H. Ritter, Liang-I Kang, Sarah Dort, Annette Robichaud, Richard Head, Michael J. Holtzman, Michael S. Diamond

Issue&Volume: 2020-08-24

Abstract: Although animal models have been evaluated for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, none have fully recapitulated the lung disease phenotypes seen in humans who have been hospitalized. Here, we evaluate transgenic mice expressing the human angiotensin I-converting enzyme 2 (ACE2) receptor driven by the cytokeratin-18 (K18) gene promoter (K18-hACE2) as a model of SARS-CoV-2 infection. Intranasal inoculation of SARS-CoV-2 in K18-hACE2 mice results in high levels of viral infection in lungs, with spread to other organs. A decline in pulmonary function occurs 4days after peak viral titer and correlates with infiltration of monocytes, neutrophils and activated T cells. SARS-CoV-2-infected lung tissues show a massively upregulated innate immune response with signatures of nuclear factor-κB-dependent, type I and II interferon signaling, and leukocyte activation pathways. Thus, the K18-hACE2 model of SARS-CoV-2 infection shares many features of severe COVID-19 infection and can be used to define the basis of lung disease and test immune and antiviral-based countermeasures.

DOI: 10.1038/s41590-020-0778-2

Source: https://www.nature.com/articles/s41590-020-0778-2