2013～2014年山东省4株柯萨奇B4型分离株遗传分析  

Genetic Analysis of Four Coxsackievirus B4 Strains Isolated from Shandong in 2013～2014,China

作　　者：王敏[1] 韦庆娟 李娟[1] 江新泉[3] 张振杰[1] 童贻刚[4] 丁淑军[5] 王显军[5] 史卫峰[1] 

机构地区：[1]泰山医学院山东省高等学校新发传染病病因流行病学实验室,泰安271000 [2]泰安市妇幼保健院,泰安271000 [3]泰山医学院公共卫生学院,泰安271016 [4]军事医学科学院微生物流行病研究所,北京100071 [5]山东省疾病预防控制中心,济南250014

出　　处：《病毒学报》2018年第1期22-29,共8页Chinese Journal of Virology

基　　金：山东省自然科学基金(项目号:ZR2015JL026),题目:通过不同性质RNA表达谱差异研究肠道病毒71型引起手足口病重症的分子机制;山东省泰山学者工程专项经费(项目号:ts201511056);山东省中医药科技发展计划(项目号:2015-259),题目:泰山紫草素抗肠道病毒及诱导细胞抗病毒相关蛋白表达的特性研究;泰安市科技发展计划(项目号:201540707),题目:应用生物信息学技术探索泰安地区肠道病毒的流行状况和传播规律~~

摘　　要：尽管柯萨奇病毒B4（Coxsackievirus B4,CVB4）分离率不高,但是在我国引起儿童脑炎的病例屡屡报道。目前人们对CVB4基因组的遗传变异了解并不多,GenBank公共数据库仅仅存储有20几个CVB4全基因组序列,分离自我国的CVB4基因组序列不足10条。本研究对2013~2014年山东省分离的4株CVB4阳性样本进行高通量测序,测得其全基因组序列,利用Mega 5.1对CVB4型毒株全基因组及VP1片段进行系统发生及同源性分析,用RDP3和SimPlot 3.5.1软件进行基因重组分析。结果显示这4株病毒为柯萨奇病毒B4（Coxsackievirus B4,CVB4）型,全基因组序列长度分别为7 372bp、7 389bp、7 389bp和7 391bp,核苷酸同源性为97.1%~99.9%,氨基酸同源性为98.5%~99.9%。与2013年温州CVB4分离株CVB4/P11/2013/China（GenBank登录号：KP289433）分离株同源性最高,核苷酸及氨基酸同源性分别为97.1%~98.3%和98.6%~99.4%。对VP1基因进行系统发育树分析表明,VP1基因可划分成5个基因型,基因型内部序列距离小于15%,而基因型间距离均大于15%。另外,4株CVB4分离株VP1的进化关系较近,同近年来国内其他分离株单成一簇,属于基因型V分支。经RDP3和SimPlot 3.5.1软件分析发现,这四个CVB4分离株均发生了基因重组,分离株SDJN/CHN/2013可能发生了两次基因重组。综上,这4个CVB4分离株基因组高度相似,均位于基因型V分支,且基因组发生了基因重组。Although the isolation rate of Coxsackievirus B4（CVB4）was low,it has been frequently reported to cause viral encephalitis in China.However,little is known regarding the evolution and variation of CVB4 and only approximately 20 full-length CVB4 genomes were deposited in GenBank,with less than ten from China.In the present study,we described four novel complete CVB4 genomes isolated from Shandong Province during 2013~2014.Phylogenetic and homology analyses were performed using the Mega 5.1 program.RDP3 and SimPlot 3.5.1 were applied to detect potential recombination events.The results showed that all of the four strains belong to Coxsackievirus B4（CVB4）and the four genomes were 7,372 bp,7,389 bp,7,389 bp and 7,391 bp in length,respectively.The nucleotide homology of the four strains ranged from 97.1% to 99.9% ,and the amino acid homology ranged from 98.5% to 99.9% .They shared the highest homology with CVB4/P11/2013/China（GenBank accession no.KP289433）,which was isolated from Wenzhou in 2013.Their nucleotide and amino acid homologies were 97.1% ~98.3% and 98.6% ~99.4% ,respectively.Phylogenetic analysis of the VP1 gene sequences showed that they could be classified into five genotypes.For these genotypes,the within group distance was〈15% ,whereas the between group distance was〉15% .In addition,the four CVB4 strains were closely related with other isolates in China in recent years and they formed a separate cluster within genotype V.Both RDP3 and SimPlot 3.5.1 analyses revealed that all of the four CVB4 isolates were recombinants,and the strain 2013/SDJN/CHN might have undergone two recombination events.In summary,the four CVB4 isolates from Shandong belong to genotype V and all of them are recombinants.

关 键 词：柯萨奇病毒B4型(CVB4) 系统发育分析 VP1 基因重组 

分 类 号：R373.23[医药卫生—病原生物学]