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《Cell，6月10日，Generation of a Broadly Useful Model for COVID-19 Pathogenesis Vaccination, and Treatment》

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

  • Generation of a Broadly Useful Model for COVID-19 Pathogenesis Vaccination, and Treatment

    Jing Sun #

    Zhen Zhuang #

    Jian Zheng #

    Paul B. McCray Jr.

    Stanley Perlman

    Jincun Zhao 11

    Published:June 10, 2020DOI:https://doi.org/10.1016/j.cell.2020.06.010

    Summary

    COVID-19, caused by SARS-CoV-2, is a virulent pneumonia, with >4,000,000 confirmed cases worldwide and >290,000 deaths as of May 15, 2020. It is critical that vaccines and therapeutics be developed very rapidly. Mice, the ideal animal for assessing such interventions, are resistant to SARS-CoV-2. Here, we overcome this difficulty by exogenous delivery of human ACE2 with a replication-deficient adenovirus (Ad5-hACE2). Ad5-hACE2-sensitized mice developed pneumonia characterized by weight loss, severe pulmonary pathology, and high-titer virus replication in lungs. Type I interferon, T cells and, most importantly, signal transducer and activator of transcription 1 (STAT1) are critical for virus clearance and disease resolution in these mice. Ad5-hACE2-transduced mice enabled rapid assessments of a vaccine candidate, of human convalescent plasma, and of two antiviral therapies (poly I:C and remdesivir). In summary, we describe a murine model of broad and immediate utility to investigate COVID-19 pathogenesis, and to evaluate new therapies and vaccines.

  • 原文来源：https://www.cell.com/cell/fulltext/S0092-8674(20)30741-8
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