美国北卡罗莱纳大学教堂山分校Ralph S. Baric课题组建立一个小鼠适应性SARS-CoV-2模型,可用于测试COVID-19的治疗措施。这一研究成果于2020年8月27日在线发表在《自然》上。
Title: A mouse-adapted model of SARS-CoV-2 to test COVID-19 countermeasures
Author: Kenneth H. Dinnon, Sarah R. Leist, Alexandra Schfer, Caitlin E. Edwards, David R. Martinez, Stephanie A. Montgomery, Ande West, Boyd L. Yount, Yixuan J. Hou, Lily E. Adams, Kendra L. Gully, Ariane J. Brown, Emily Huang, Matthew D. Bryant, Ingrid C. Choong, Jeffrey S. Glenn, Lisa E. Gralinski, Timothy P. Sheahan, Ralph S. Baric
Issue&Volume: 2020-08-27
Abstract: Coronaviruses are prone to emergence into new host species most recently evidenced by SARS-CoV-2, the causative agent of the COVID-19 pandemic1. Small animal models that recapitulate SARS-CoV-2 disease are desperately needed to rapidly evaluate medical countermeasures (MCMs)2,3. SARS-CoV-2 cannot infect wildtype laboratory mice due to inefficient interactions between the viral spike (S) protein and the murine ortholog of the human receptor, ACE24. We used reverse genetics5 to remodel the interaction between S and mACE2 resulting in a recombinant virus (SARS-CoV-2 MA) that could utilize mACE2 for entry. SARS-CoV-2 MA replicated in both the upper and lower airways of both young adult and aged BALB/c mice. Importantly, disease was more severe in aged mice, and showed more clinically relevant phenotypes than those seen in HFH4-hACE2 transgenic mice. We then demonstrated the utility of this model through vaccine challenge studies in immune competent mice with native expression of mACE2. Lastly, we show that clinical candidate interferon (IFN) lambda-1a can potently inhibit SARS-CoV-2 replication in primary human airway epithelial cells in vitro, and both prophylactic and therapeutic administration diminished replication in mice. Our mouse-adapted SARS-CoV-2 model demonstrates age-related disease pathogenesis and supports the clinical use of pegylated IFN lambda-1a treatment in human COVID-19 infections6.
DOI: 10.1038/s41586-020-2708-8
Source: https://www.nature.com/articles/s41586-020-2708-8
Nature:《自然》,创刊于1869年。隶属于施普林格·自然出版集团,最新IF:69.504
官方网址:http://www.nature.com/
投稿链接:http://www.nature.com/authors/submit_manuscript.html
本期文章:《自然》:Online/在线发表