C*I
发帖数: 4736 | 1 【 以下文字转载自 Joke 讨论区 】
发信人: Huangchong (净坛使者), 信区: Joke
标 题: 石正丽2015论文
发信站: BBS 未名空间站 (Thu Feb 6 19:21:33 2020, 美东)
摘要
sars和mers的出现表明跨物种传播病毒对人类具有威胁。
这里我们研究一种在中国马蹄蝙蝠里流行的SARS-相似病毒，SHC014。
使用SARS冠毒的反向遗传系统，我们把SHC014的spike蛋白装在了一个可以在老鼠里复
制的SARS病毒框架上，并对它进行了一些研究。这些结果显示，SHC014所属的2b类病毒
可以使用SARS的人类受体，ACE2。这种病毒可以在来自人的呼吸道的原代细胞里高效增
殖，达到跟SARS病毒类似的病毒滴度。而且，体内实验表明这个人工病毒可以在老鼠肺
里产生病理效果。
对现有的抗SARS免疫疗法和其他疗法的测试显示，这些方法都不太有效。抗SARS的单抗
没有中和病毒，抗SARS的疫苗没有产生有效的免疫效果。
（总结）我们造了一种全长的SHC014重组病毒，并证明它可以在老鼠体内和细胞培养的
条件下有效复制。我们的工作提示SARS有可能再次从蝙蝠病毒传到人类。
（说明：反向遗传系统是Baric发明的，可以从DNA造冠毒RNA的系统。Baric是长期研究
冠毒的专家，在sars之前研究老鼠肝炎病毒MHV。2017年说人民的媳妇儿对冠毒也广泛
有效的文章也有他。）
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 populations1. Using the SARS-
CoV reverse genetics system2, 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.
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