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研究领域农业,兽医和食品科学兽医科学兽医病毒学
一种适应SARS-CoV-2的小鼠模型来测试COVID-19的对策

一种适应SARS-CoV-2的小鼠模型来测试COVID-19的对策

Kenneth H Dinnon ¹, Sarah R Leist ², Alexandra Schäfer ², Caitlin E Edwards ², David R Martinez ², Stephanie A Montgomery ³, Ande West ², Boyd L Yount ², Yixuan J Hou ², Lily E Adams ¹, Kendra L Gully ², Ariane J Brown ², Emily Huang ², Matthew D Bryant ⁴, Ingrid C Choong ⁴, Jeffrey S Glenn ^5,6, Lisa E Gralinski ², Timothy P Sheahan ², Ralph S Baric ^7,8,9

Kenneth H Dinnon ¹, Sarah R Leist ², Alexandra Schäfer ²

¹Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
²Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
³Department of Pathology and Laboratory Medicine, University of North Carolina, Chapel Hill, NC, USA.
⁴Eiger BioPharmaceuticals, Palo Alto, CA, USA.
⁵Departments of Medicine and Microbiology and Immunology, Stanford University, Stanford, CA, USA.
⁶Palo Alto Veterans Administration, Palo Alto, CA, USA.
⁷Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA. rbaric@email.unc.edu.
⁸Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA. rbaric@email.unc.edu.
⁹Rapidly Emerging Antiviral Drug Discovery Initiative, University of North Carolina, Chapel Hill, NC, USA. rbaric@email.unc.edu.

⁰Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.

Nature +

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2020年八月28日

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在PubMed上查看摘要

概括

此摘要是机器生成的。

研究人员开发了一种适应鼠标的SARS-CoV-2 (MA) 模型,以研究COVID-19的病原和测试治疗方法. 这种新模型显示了与年龄相关的疾病严重程度,并支持干扰素lambda1a作为潜在的治疗方法.

科学领域

病毒学
免疫学
病变发生

背景情况

严重急性呼吸道综合征冠状病毒2 (SARS-CoV-2) 是导致COVID-19大流行的原因.
小动物模型对于评估针对SARS-CoV-2的医疗对策至关重要.
野生类型的小鼠不易感染SARS-CoV-2 由于尖端蛋白与ACE2的相互作用不兼容.

研究的目的

为研究COVID-19创建一个适应鼠标的SARS-CoV-2 (MA) 模型.
在小鼠模型中研究与年龄相关的疾病严重程度.
评估干扰素-lambda1a (IFN-λ1a) 作为COVID-19治疗的疗效.

主要方法

使用逆转基因设计SARS-CoV-2以使用小鼠ACE2.
在年轻和老年BALB/c小鼠中复制SARS-CoV-2 MA.
进行的疫苗挑战研究和体外/体内IFN-λ1a治疗实验.

主要成果

在老鼠的呼吸道中复制SARS-CoV-2 MA,并在老鼠中引起更严重的疾病.
该MA模型表现出临床相关的表型,优于现有的转基因模型.
IFN-λ1a在人类细胞和小鼠中显示出强大的SARS-CoV-2复制抑制作用.

结论

适应小鼠的SARS-CoV-2 MA模型有效地回顾了COVID-19的发病过程,包括与年龄相关的差异.
这种模型支持基化IFN-λ1a作为人类COVID-19的可行的治疗方法的开发.

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