一组类似SARS的循环蝙蝠冠状病毒显示出出现人间传播的可能性。

A SARS-like cluster of circulating bat coronaviruses shows potential for human emergence.

作者信息

Menachery Vineet D, Yount Boyd L, Debbink Kari, Agnihothram Sudhakar, Gralinski Lisa E, Plante Jessica A, Graham Rachel L, Scobey Trevor, Ge Xing-Yi, Donaldson Eric F, Randell Scott H, Lanzavecchia Antonio, Marasco Wayne A, Shi Zhengli-Li, Baric Ralph S

机构信息

Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.

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

出版信息

Nat Med. 2015 Dec;21(12):1508-13. doi: 10.1038/nm.3985. Epub 2015 Nov 9.

Abstract

The emergence of severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome (MERS)-CoV underscores the threat of cross-species transmission events leading to outbreaks in humans. Here we examine the disease potential of a SARS-like virus, SHC014-CoV, which is currently circulating in Chinese horseshoe bat populations. Using the SARS-CoV reverse genetics system, we generated and characterized a chimeric virus expressing the spike of bat coronavirus SHC014 in a mouse-adapted SARS-CoV backbone. The results indicate that group 2b viruses encoding the SHC014 spike in a wild-type backbone can efficiently use multiple orthologs of the SARS receptor human angiotensin converting enzyme II (ACE2), replicate efficiently in primary human airway cells and achieve in vitro titers equivalent to epidemic strains of SARS-CoV. Additionally, in vivo experiments demonstrate replication of the chimeric virus in mouse lung with notable pathogenesis. Evaluation of available SARS-based immune-therapeutic and prophylactic modalities revealed poor efficacy; both monoclonal antibody and vaccine approaches failed to neutralize and protect from infection with CoVs using the novel spike protein. On the basis of these findings, we synthetically re-derived an infectious full-length SHC014 recombinant virus and demonstrate robust viral replication both in vitro and in vivo. Our work suggests a potential risk of SARS-CoV re-emergence from viruses currently circulating in bat populations.

摘要

严重急性呼吸综合征冠状病毒(SARS-CoV)和中东呼吸综合征冠状病毒(MERS-CoV)的出现凸显了跨物种传播事件导致人类疫情爆发的威胁。在此,我们研究了一种类似SARS的病毒SHC014-CoV的致病潜力,该病毒目前在中国马蹄蝠种群中传播。利用SARS-CoV反向遗传学系统,我们构建并鉴定了一种嵌合病毒,该病毒在适应小鼠的SARS-CoV骨架中表达蝙蝠冠状病毒SHC014的刺突蛋白。结果表明,在野生型骨架中编码SHC014刺突蛋白的2b组病毒能够有效利用SARS受体人类血管紧张素转换酶II(ACE2)的多个直系同源物,在原代人气道细胞中高效复制,并达到与SARS-CoV流行株相当的体外滴度。此外,体内实验证明嵌合病毒在小鼠肺中复制,并具有明显的致病性。对现有的基于SARS的免疫治疗和预防方法的评估显示效果不佳;单克隆抗体和疫苗方法均无法中和并预防使用新型刺突蛋白的冠状病毒感染。基于这些发现,我们人工合成并重新获得了一种具有感染性的全长SHC014重组病毒,并证明其在体外和体内均能强劲复制。我们的研究表明,目前在蝙蝠种群中传播的病毒存在SARS-CoV再次出现的潜在风险。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/080a/7095877/c917cb6c4440/41591_2015_Article_BFnm3985_Fig1_HTML.jpg

文献AI研究员

20分钟写一篇综述,助力文献阅读效率提升50倍

立即体验

用中文搜PubMed

大模型驱动的PubMed中文搜索引擎

马上搜索