埃博拉病毒2014年毒株的基因组变异特征分析

Characteristics of genome variations of Ebola viruses in 2014 epidemic

目的通过对埃博拉病毒2014年毒株基因组共102株序列的分析,研究其变异特征,探讨病毒基因组变异与其流行病学特征改变之间的关系。方法选取NCBI公共数据库中埃博拉病毒全基因组序列,应用Mummer3.0软件分析病毒基因组变异特征;使用MEGA5软件进行蛋白进化分析;应用CPHmodels和PyMOL软件,根据蛋白同源性模拟蛋白的三维构型。结果埃博拉病毒2014年毒株(扎伊尔型)基因组中,共有606个位点发生变异,其中有49个变异位点是2014年毒株特有的、并导致所编码的氨基酸发生非同义突变。特别是NP蛋白第128位、GP蛋白第82位和L蛋白第1 951位氨基酸,不仅在2014年之前所有的扎伊尔型毒株中是保守不变的,而且在其余埃博拉病毒亚型之间也是高度保守的,但在2014年毒株中却发生了特异性的变异。结论埃博拉病毒2014年毒株基因组具有独特的变异特征,使得NP、GP和L蛋白发生变异,特别是GP蛋白第82位氨基酸由丙氨酸突变为缬氨酸,将影响其所在的α螺旋的稳定性,这可能是2014年毒株致死能力减弱和传播能力增强的原因之一。基因组变异是否直接导致此次疫情中病毒流行病学特征改变,还需要进一步的实验研究证实。

Objective To explore the relationship between the Ebola virus genome variations and its epidemiological characteristics by analyzing the 102 whole genome sequences of Ebola viruses in 2014 outbreak.Methods Whole genome sequences of Ebola viruses（EBOVs）were obtained from the NCBI database,and the variations in genome sequences were analyzed by Mummer3.0.The evolutionary analysis was carried out through MEGA5;and the 3D modeling of the protein was performed using CPHmodels and PyMOL software.Results It was found that there were 606 single nucleotide variants（SNVs）in the genome of 2014 EBOVs,of which 49 nonsynonymous SNVs were unique.The amino acids of NP-182,GP-82 and L-1951,which were highly conserved not only among all the Zaire EBOVs before 2014,but also among different EBOV species,were altered in 2014 EBOVs.Conclusion The unique mutation of 2014 EBOVs resulting in alterations of NP,GP and L protein,especially the alteration of aa82 of GP（AlaVal）,might weaken the stability ofα-helix where the amino acid is located,which might be associated with the weakened lethality and enhanced transmission of the virus.Further studies are needed to confirm whether genomic variations in 2014 EBOVs is responsible for change of the epidemiological characteristics.