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《Cell，6月10日，A SARS-CoV-2 infection model in mice demonstrates protection by neutralizing antibodies》

  • 来源专题：COVID-19科研动态监测
  • 编译者： zhangmin
  • 发布时间：2020-06-11

  • A SARS-CoV-2 infection model in mice demonstrates protection by neutralizing antibodies

    Ahmed O. Hassan ∗

    James Brett Case ∗

    Emma S. Winkler ∗

    Michael J. Holtzman

    Ali H. Ellebedy

    Michael S. Diamond ¶

    Published:June 10, 2020DOI:https://doi.org/10.1016/j.cell.2020.06.011

    Abstract

    Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a pandemic with millions of human infections. One limitation to the evaluation of potential therapies and vaccines to inhibit SARS-CoV-2 infection and ameliorate disease is the lack of susceptible small animals in large numbers. Commercially available laboratory strains of mice are not readily infected by SARS-CoV-2 because of species-specific differences in their angiotensin-converting enzyme 2 (ACE2) receptors. Here, we transduced replication-defective adenoviruses encoding human ACE2 via intranasal administration into BALB/c mice and established receptor expression in lung tissues. hACE2-transduced mice were productively infected with SARS-CoV-2, and this resulted in high viral titers in the lung, lung pathology, and weight loss. Passive transfer of a neutralizing monoclonal antibody reduced viral burden in the lung and mitigated inflammation and weight loss. The development of an accessible mouse model of SARS-CoV-2 infection and pathogenesis will expedite the testing and deployment of therapeutics and vaccines.

  • 原文来源：https://www.cell.com/cell/fulltext/S0092-8674(20)30742-X
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    • 来源专题：COVID-19科研动态监测
    • 编译者：xuwenwhlib
    • 发布时间：2020-06-09
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  • 《CELL，5月26日，A mouse model of SARS-CoV-2 infection and pathogenesis》
    • 来源专题：COVID-19科研动态监测
    • 编译者：xuwenwhlib
    • 发布时间：2020-05-27
    • A mouse model of SARS-CoV-2 infection and pathogenesis Shi-Hui Sun 7 Qi Chen 7 Hong-Jing Gu 7 Yu-Sen Zhou Cheng-Feng Qin You-Chun Wang 8 Show all authors Show footnotes Published:May 26, 2020DOI:https://doi.org/10.1016/j.chom.2020.05.020 Summary 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 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) using CRISPR/Cas9 knock-in technology. Compared 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 evidenced 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.
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