Menachery Vineet D, Yount Boyd L, Sims Amy C, Debbink Kari, Agnihothram Sudhakar S, Gralinski Lisa E, Graham Rachel L, Scobey Trevor, Plante Jessica A, Royal Scott R, Swanstrom Jesica, Sheahan Timothy P, Pickles Raymond J, Corti Davide, Randell Scott H, Lanzavecchia Antonio, Marasco Wayne A, Baric Ralph S
Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599;
Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599; Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599;
Proc Natl Acad Sci U S A. 2016 Mar 15;113(11):3048-53. doi: 10.1073/pnas.1517719113. Epub 2016 Mar 14.
Outbreaks from zoonotic sources represent a threat to both human disease as well as the global economy. Despite a wealth of metagenomics studies, methods to leverage these datasets to identify future threats are underdeveloped. In this study, we describe an approach that combines existing metagenomics data with reverse genetics to engineer reagents to evaluate emergence and pathogenic potential of circulating zoonotic viruses. Focusing on the severe acute respiratory syndrome (SARS)-like viruses, the results indicate that the WIV1-coronavirus (CoV) cluster has the ability to directly infect and may undergo limited transmission in human populations. However, in vivo attenuation suggests additional adaptation is required for epidemic disease. Importantly, available SARS monoclonal antibodies offered success in limiting viral infection absent from available vaccine approaches. Together, the data highlight the utility of a platform to identify and prioritize prepandemic strains harbored in animal reservoirs and document the threat posed by WIV1-CoV for emergence in human populations.
人畜共患病源引发的疫情对人类疾病和全球经济都构成威胁。尽管有大量宏基因组学研究，但利用这些数据集来识别未来威胁的方法仍不完善。在本研究中，我们描述了一种将现有宏基因组学数据与反向遗传学相结合的方法，以构建试剂来评估正在传播的人畜共患病毒的出现及致病潜力。以严重急性呼吸综合征（SARS）样病毒为重点，结果表明WIV1冠状病毒（CoV）簇有直接感染人类的能力，并且可能在人群中发生有限传播。然而，体内减毒表明还需要进一步适应才能引发流行病。重要的是，现有的SARS单克隆抗体成功地限制了病毒感染，而现有的疫苗方法则无法做到这一点。这些数据共同凸显了一个平台在识别动物宿主中存在的大流行前菌株并对其进行优先排序方面的效用，并记录了WIV1-CoV在人群中出现所带来的威胁。
