Cell · 2020
Generation of a Broadly Useful Model for COVID-19 Pathogenesis, Vaccination, and Treatment.
СтатьяПоддержка NIH: внешняя программаПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод пока не подготовлен
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Sun Jing, Zhuang Zhen, Zheng Jian, Li Kun, Wong Roy Lok-Yin, Liu Donglan, Huang Jicheng, He Jiangping, Zhu Airu, Zhao Jingxian, Li Xiaobo, Xi Yin, Chen Rongchang, Alshukairi Abeer N, Chen Zhao, Zhang Zhaoyong, Chen Chunke, Huang Xiaofang, Li Fang, Lai Xiaomin, Chen Dingbin, Wen Liyan, Zhuo Jianfen, Zhang Yanjun, Wang Yanqun, Huang Shuxiang, Dai Jun, Shi Yongxia, Zheng Kui, Leidinger Mariah R, Chen Jiekai, Li Yimin, Zhong Nanshan, Meyerholz David K, McCray Paul B, Perlman Stanley, Zhao Jincun
Аннотация
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.
Предметные рубрики MeSH
Angiotensin-Converting Enzyme 2AnimalsBetacoronavirusCOVID-19Chlorocebus aethiopsCoronavirus InfectionsDisease Models, AnimalDrug Evaluation, PreclinicalFemaleHumansInterferon-gammaLungMaleMiceMice, Inbred BALB CMice, Inbred C57BLMice, KnockoutPandemicsPeptidyl-Dipeptidase APneumonia, ViralReceptor, Interferon alpha-betaSARS-CoV-2STAT1 Transcription FactorSpecific Pathogen-Free OrganismsTransduction, GeneticVaccinationVero CellsViral LoadVirus Replication