Generation of a Broadly Useful Model for COVID-19 Pathogenesis, Vaccination, and Treatment
Generation of a Broadly Useful Model for COVID-19 Pathogenesis, Vaccination, and Treatment
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DOI：
10.1016/j.cell.2020.06.010
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发表时间：
2020-08-06
期刊：
影响因子：
64.5
通讯作者：
Zhao, Jincun
中科院分区：
文献类型：
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作者：
Sun, Jing;Zhuang, Zhen;Zhao, Jincun
由SARS-CoV-2引起的COVID-19是一种剧毒肺炎，截至2020年5月15日，全球确诊病例为1.04亿例，死亡病例为1.29万例。至关重要的是，疫苗和治疗方法必须迅速发展。小鼠是评估此类干预措施的理想动物，它们对SARS-CoV-2具有抵抗力。在这里，我们克服了这一困难，通过外源性传递人ACE2与复制缺陷腺病毒（Ad5-hACE2）。ad5 - hace2致敏小鼠出现以体重减轻、严重肺部病理和肺部高滴度病毒复制为特征的肺炎。在这些小鼠中，I型干扰素、T细胞，以及最重要的信号换能器和转录激活因子1 （STAT1）对病毒清除和疾病解决至关重要。ad5 - hace2转导小鼠能够快速评估一种候选疫苗、人类恢复期血浆和两种抗病毒疗法（poly I:C和remdesivir）。总之，我们描述了一种广泛而直接实用的小鼠模型，用于研究COVID-19的发病机制和评估新的治疗方法和疫苗。
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 byweight 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.