中东呼吸综合征冠状病毒刺突蛋白特征分析

Analysis of the characteristics of the spike protein of the Middle East respiratory syndrome coronavirus

目的研究中东呼吸综合症病毒刺突蛋白的流行特点。方法从美国生物信息中心（NCBI）下载2012年以来流行的中东呼吸综合症病毒刺突蛋白氨基酸序列,通过生物信息学手段（多序列比对和蛋白进化树）分析中东呼吸综合症病毒刺突蛋白氨基酸序列的流行特征。结果 1）2012年以来中东呼吸综合症病毒流行以来刺突蛋白氨基酸序列呈现出一定的地域性特点,其中来自法国的人源刺突蛋白序列之间的同源性为99.70%~100%,来自阿拉伯联合酋长国的刺突蛋白序列之间的同源性为99.63%~100%,来自2014年阿拉伯联合酋长国的刺突蛋白序列在同一进化树分枝上。2）来自沙特阿拉伯的人源刺突蛋白序列未表现出时间上的差异,2013、2014和2015年分离株刺突蛋白的同源性为99.63%~100%,但是来自沙特阿拉伯的刺突蛋白与来自法国和阿拉伯联合酋长国的刺突蛋白区别明显;在进化树上,来自沙特阿拉伯的呼吸综合症病毒刺突蛋白氨基酸序列并没有完全聚在相同的进化分枝上,而是分散在相对集中的不同分枝上。3）2014年3、5、6月来自美国的3条刺突蛋白序列之间的同源性为99.70%~99.85%低于和来自沙特阿拉伯的人源刺突蛋白之间的同源性（99.70%~100%）。4）不同宿主间来源株的刺突蛋白序列之间无明显区别,其中单峰驼来源的刺突蛋白序列间的同源性为98.15%~100%,其与人源刺突蛋白序列之间的同源性为99.56%~100%,单峰驼源的刺突蛋白序列在进化树上分散在沙特阿拉伯人源刺突蛋白分枝上。5）英格兰分离株刺突蛋白之间的同源性为99.70%~99.93%,低于和分离较晚的几条源于沙特阿拉伯的人源刺突蛋白之间的同源性（100%）,而与分离较早的来自沙特阿拉伯的刺突蛋白氨基酸序列（Seq36,Seq51）的同源性较低（99.78%~99.93%）,且分散在不同的分枝上。6）来源于韩国分离株的一刺突蛋白与其他刺突蛋白之间的同源性最高为99.78%,处于单独分支上。7）来自中国分离株的刺突蛋白序列与来自英格兰以及沙特阿拉伯部分人源刺突蛋白序列同源性为100%。结论地区间中东呼吸综合症病毒刺突蛋白的同源性很高,达98.15%~100%,说明刺突蛋白氨基酸序列非常保守。本次流行的中东呼吸综合症冠状病毒在同一地域内有多种不同的病毒株流行,多地可能同时存在中东呼吸综合症流行,也同时存在地区间输入性快速传播;同一地区不同年份病毒的刺突蛋白变异不明显,不同宿主间的病毒刺突蛋白序列无显著差别。

Objective To study the characteristics of the spike（S）protein of the Middle East respiratory syndrome coronavirus（MERS-CoV）. Methods Amino acid sequences of the S protein of the MERS-CoV that were submitted to NCBI since 2012 were downloaded and the characteristics of the S protein were studied bioinformatically. Results 1）Amino acid sequences of the S protein of the MERS-CoV displayed several regional characteristics after 2012.Amino acid sequences of the S protein of the MERS-CoV that infected humans in France had a similarity of 99.70%-100%.Amino acid sequences of the S protein of the MERS-CoV isolated in the United Arab Emirates had a similarity of 99.63%-100%.Amino acid sequences of the S protein of the MERS-CoV that was isolated in the United Arab Emirates in 2014 were on the same evolutionary tree branch.2）Amino acid sequences of the S protein of the MERS-CoV that was isolated in Saudi Arabia in 2013,2014,and 2015 had a similarity of 99.63%-100%.The amino acid sequences did not vary over time but they did differ markedly from amino acid sequences of the S protein of the MERS-CoV that was isolated in France and the United Arab Emirates.MERS-CoV that was isolated in Saudi Arabia was not concentrated on the same evolutionary tree branch but on different branches.3）Three amino acid sequences of the S protein of the MERS-CoV that was isolated in the US in March,May,and June 2012 had a lower level of similarity（99.70%-99.85%）than did the MERSCoV that was isolated in Saudi Arabia（99.70%-100%）.4）There were no significant differences in amino acid sequences of the S protein of the MERS-CoV isolated from different hosts（humans and camels）.Amino acid sequences of the S protein of the MERS-CoV isolated from camels had a similarity of 98.15%-100%.Amino acid sequences of the S protein of the MERS-CoV isolated from humans and amino acid sequences of the S protein of the MERS-CoV that was isolated from camels had a similarity of 99.56%-100%.The MERS-CoV that was isolated from camels in Saudi Arabia was scattered along the same evolutionary tree branch.5）Amino acid sequences of the S protein of the MERS-CoV that was isolated in the UK had a similarity of 99.70%-99.93%.This level of similarity was lower than that of amino acid sequences of the S protein of the MERS-CoV that was later isolated in Saudi Arabia（100%）.However,there was less similarity（99.78%-99.93%）between the amino acid sequences of the S protein of the MERS-CoV that was isolated in the UK and some of the amino acid sequences of the S protein（Seq36and Seq51）of the MERS-CoV that was isolated early in Saudi Arabia.The MERS-CoV that was isolated in the UK was scattered on different evolutionary tree branches.6）Amino acid sequences of the S protein of the MERS-CoV that was isolated in South Korea only had a similarity of 99.78%to other amino acid sequences of the S protein of the MERS-CoV that was isolated elsewhere.The MERS-CoV that was isolated in South Korea was located on an evolutionary tree branch by itself.7）The amino acid sequences of the S protein of the MERS-CoV that infected humans in China was 100%similar to amino acid sequences of the S protein of the MERSCoV that was isolated in the UK and amino acid sequences of the S protein of some of the MERS-CoV strains that infected humans in Saudi Arabia. Conclusion Amino acid sequences of the S protein of the MERS-CoV that was isolated from different areas had a high level of similarity（reaching 98.15%-100%）,indicating that amino acid sequences of the S protein were highly conserved.Many strains of the MERS-CoV were prevalent in a given region.The MERS-CoV may be prevalent at the same time in many regions and may quickly spread from one region to another.There was little variation in the amino acid sequences of the S protein of the MERS-CoV in the same region at different times,and there was little variation in the amino acid sequences of the S protein of the MERS-CoV that infected different hosts.