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中外科学家合作建立新冠感染非转基因小鼠模型

本期文章:《细胞》:Online/在线发表

广州医科大学第一附属医院赵金存、美国爱荷华大学Stanley Perlman、Paul B. McCray Jr.等研究人员合作开发了新冠感染非转基因小鼠模型。这一研究成果于2020年6月10日在线发表在《细胞》上。

研究人员通过复制缺陷型腺病毒(Ad5-hACE2)外源递送人ACE2克服了这一困难。Ad5-hACE2感染的小鼠出现了肺炎,其特征在于体重减轻、严重的肺部病理以及肺部高滴度病毒复制。I型干扰素、T细胞以及信号转导和转录激活因子1(STAT1)对于这些小鼠的病毒清除和疾病缓解至关重要。Ad5-hACE2转导的小鼠能够快速评估候选疫苗、人类恢复期血浆以及两种抗病毒疗法(poly I:C和remdesivir)。

 

总之,研究人员描述了一种具有广泛和直接实用性的鼠模型,可用于研究COVID-19的发病机理,并评估新的疗法和疫苗。

 

附:英文原文

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

Author: Jing Sun, Zhen Zhuang, Jian Zheng, Kun Li, Roy Lok-Yin Wong, Donglan Liu, Jicheng Huang, Jiangping He, Airu Zhu, Jingxian Zhao, Xiaobo Li, Yin Xi, Rongchang Chen, Abeer N. Alshukairi, Zhao Chen, Zhaoyong Zhang, Chunke Chen, Xiaofang Huang, Fang Li, Xiaomin Lai, Dingbin Chen, Liyan Wen, Jianfen Zhuo, Yanjun Zhang, Yanqun Wang, Shuxiang Huang, Jun Dai, Yongxia Shi, Kui Zheng, Mariah R. Leidinger, Jiekai Chen, Yimin Li, Nanshan Zhong, David K. Meyerholz, Paul B. McCray, Stanley Perlman, Jincun Zhao

Issue&Volume: 2020-06-10

Abstract: 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.

DOI: 10.1016/j.cell.2020.06.010

Source: https://www.cell.com/cell/fulltext/S0092-8674(20)30741-8

期刊信息

Cell:《细胞》,创刊于1974年。隶属于细胞出版社,最新IF:36.216

官方网址:https://www.cell.com/

投稿链接:https://www.editorialmanager.com/cell/default.aspx

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