A complete sequence and comparative analysis of a SARS-associated virus (Isolate BJ01)

A complete sequence and comparative analysis of a SARS-associated virus (Isolate BJ01)
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DOI:
10.1007/bf03184203
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发表时间:
2003-05-01
影响因子:
--
通讯作者:
Yang, HM
Yang, HM
中科院分区:
其他
文献类型:
--
作者:
Qin, E;Zhu, QY;Yang, HM

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严重急性呼吸综合征(SARS)相关病毒的基因组序列为鉴定病原体、探索病原学和进化、解释传播和发病机制、开发诊断方法、通过未来疫苗接种进行预防以及通过开发新药进行治疗提供了重要信息。我们报告了被认为是SARS病原体的冠状病毒分离物(BJ01)的完整基因组序列和比较分析。基因组的大小为29725nt,有11个orf(开放阅读框)。它由一个稳定区编码一个RNA依赖的RNA聚合酶(由2个orf组成)和一个可变区代表4个CDSs(编码序列)的病毒结构基因(S, E, M, N蛋白)和5个PUPs(假定的未表征蛋白)组成。它的基因顺序与其他已知冠状病毒相同。与所有已知RNA病毒的序列比对表明该病毒属于冠状病毒科成员。通过对GenBank中5种sars相关病毒基因组序列的比较分析,确定了30个假定的替换。其中15种可能导致蛋白质中氨基酸的变化(非同义突变)。在被认为参与病毒与其宿主之间免疫反应的S蛋白中,已检测到三个氨基酸变化,并预测其物理和化学特征的改变。在M蛋白中检测到两个氨基酸的变化,这可能与病毒包膜的形成有关。系统发育分析显示,sars相关病毒可能来自非人类,但没有证据表明它们是人造的。进一步的工作应侧重于确定sars相关病毒的病因,并最终排除其他可能的sars相关病原体的存在。
The genome sequence of the Severe Acute Respiratory Syndrome (SARS)-associated virus provides essential information for the identification of pathogen(s), exploration of etiology and evolution, interpretation of transmission and pathogenesis, development of diagnostics, prevention by future vaccination, and treatment by developing new drugs. We report the complete genome sequence and comparative analysis of an isolate (BJ01) of the coronavirus that has been recognized as a pathogen for SARS. The genome is 29725 nt in size and has 11 ORFs (Open Reading Frames). It is composed of a stable region encoding an RNA-dependent RNA polymerase (composed of 2 ORFs) and a variable region representing 4 CDSs (coding sequences) for viral structural genes (the S, E, M, N proteins) and 5 PUPs (putative uncharacterized proteins). Its gene order is identical to that of other known coronaviruses. The sequence alignment with all known RNA viruses places this virus as a member in the family of Coronaviridae. Thirty putative substitutions have been identified by comparative analysis of the 5 SARS-associated virus genome sequences in GenBank. Fifteen of them lead to possible amino acid changes (non-synonymous mutations) in the proteins. Three amino acid changes, with predicted alteration of physical and chemical features, have been detected in the S protein that is postulated to be involved in the immunoreactions between the virus and its host. Two amino acid changes have been detected in the M protein, which could be related to viral envelope formation. Phylogenetic analysis suggests the possibility of non-human origin of the SARS-associated viruses but provides no evidence that they are man-made. Further efforts should focus on identifying the etiology of the SARS-associated virus and ruling out conclusively the existence of other possible SARS-related pathogen(s).