A SARS-like cluster of circulating bat coronaviruses shows potential for human emergence.
A SARS-like cluster of circulating bat coronaviruses shows potential for human emergence.
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DOI：
10.1038/nm.3985
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发表时间：
2015-12
期刊：
影响因子：
82.9
通讯作者：
Baric RS
中科院分区：
文献类型：
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作者：
Menachery VD;Yount BL Jr;Debbink K;Agnihothram S;Gralinski LE;Plante JA;Graham RL;Scobey T;Ge XY;Donaldson EF;Randell SH;Lanzavecchia A;Marasco WA;Shi ZL;Baric RS
Ralph Baric、Vineet Menachery及其同事对在中国马蹄蝠中传播的一种类似sars的冠状病毒进行了表征，以确定其感染人类初级气道上皮细胞、引起小鼠疾病并对现有治疗产生反应的可能性。本文的在线版本（doi:10.1038/nm.3985）包含补充材料，可供授权用户使用。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间疫情的威胁。在这里，我们研究了一种sars样病毒SHC014-CoV的潜在疾病，该病毒目前在中国马蹄蝠种群中传播。利用SARS-CoV反向遗传系统，我们在小鼠适应的SARS-CoV主干中产生了表达蝙蝠冠状病毒SHC014刺突的嵌合病毒并进行了鉴定。结果表明，在野生型主干编码SHC014尖峰的2b组病毒可以有效地利用SARS受体人血管紧张素转换酶II （ACE2）的多个同源物，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，体内实验表明嵌合病毒在小鼠肺中的复制具有明显的发病机制。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都不能中和和保护使用新型刺突蛋白的冠状病毒感染。在这些发现的基础上，我们合成了一种传染性的SHC014全长重组病毒，并在体外和体内证明了病毒的强大复制能力。我们的工作表明，目前在蝙蝠种群中传播的病毒存在sars冠状病毒再次出现的潜在风险。本文的在线版本（doi:10.1038/nm.3985）包含补充材料，可供授权用户使用。
Ralph Baric, Vineet Menachery and colleagues characterize a SARS-like coronavirus circulating in Chinese horseshoe bats to determine its potential to infect primary human airway epithelial cells, cause disease in mice and respond to available therapeutics. The online version of this article (doi:10.1038/nm.3985) contains supplementary material, which is available to authorized users. 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. The online version of this article (doi:10.1038/nm.3985) contains supplementary material, which is available to authorized users.