柯萨奇病毒A组6型中国株的分子进化和时空传播分析  

Molecular evolution and spatiotemporal transmission analysis of Chinese isolates of coxsackievirus A6

作　　者：贾永涛 唐佳婕 王惠 董长征 JIA Yongtao;TANG Jiajie;WANG Hui;DONG Changzheng(Health Science Center,Ningbo University,Ningbo 315211,China;Zhejiang Provincial Key Laboratory of Pathological and Physiological Technology,Ningbo 315211,China)

机构地区：[1]宁波大学医学部,浙江宁波315211 [2]浙江省病理生理学技术研究重点实验室,浙江宁波315211

出　　处：《宁波大学学报（理工版）》2024年第1期84-92,共9页Journal of Ningbo University：Natural Science and Engineering Edition

基　　金：浙江省基础公益研究计划(LGF18C060001);宁波市公益类科技计划(2021S135)。

摘　　要：柯萨奇病毒A组6型(Coxsackievirus A6,CV-A6)是手足口病的主要病原体,可引起非典型手足口病和中枢神经系统疾病,对儿童造成严重的疾病负担,尚无上市的疫苗和抗病毒药物.基于3288条CV-A6中国株VP1序列,利用Nextstrain平台的augur病原体生物信息分析包,构建了CV-A6的时间尺度分子进化树,确定了进化分支和分支突变,分析了分支突变与抗原表位之间的联系.进一步分析了CV-A6中国株各分支在中国七大地理区域的时空分布和优势分支,绘制了主要分支的时空传播路线.结果发现,CV-A6中国株主要分为B、C和D三个进化分支以及D2、D3a和D3b三个子分支,抗原表位处的突变形成了新的进化分支,促进了病毒的流行.华南和华东是CV-A6中国株的主要起源地,华南和华东相互输出、华东输出全国是中国株的主要传播模式.对CV-A6中国株的分子进化和时空传播分析,为CV-A6引起的手足口病等疫情的监测、预警和防控提供了重要支持.Coxsackievirus A6(CV-A6)is the main pathogen of hand-foot-mouth disease(HFMD),which can cause atypical HFMD and central neurological diseases.It imposes a significant disease burden on children,and there are currently no licensed vaccines or antiviral drugs available.Based on 3288 VP1 sequences of CV-A6 isolates from China,a time-scaled molecular evolution tree of CV-A6 was constructed with the augur package on the Nextstrain platform.Evolutionary clades and clade mutations were identified,and the relationship between clade mutations and antigenic epitopes was analyzed.Furthermore,the spatiotemporal distribution and dominant clades of CV-A6 isolates in seven geographical regions of China were analyzed,and the spatiotemporal transmission routes of the main clades were mapped.The results revealed that CV-A6 isolates in China were mainly divided into three evolutionary clades,B,C,and D.Three sub-clades were D2,D3a,and D3b.Mutations at antigenic epitopes have formed new evolutionary clades,promoting the spread of the virus.Southern China and Eastern China are the main origins of CV-A6 isolates,and the major transmission pattern involves mutual dissemination between Southern and Eastern China.Eastern China serves as a nationwide source of transmission.The molecular evolution and spatiotemporal transmission analysis of CV-A6 isolates in China provides important support for the surveillance,early warning,and prevention of outbreaks of HFMD and other diseases caused by CV-A6.

关 键 词：柯萨奇病毒A组6型 肠道病毒 分子进化 时空传播分析 生物信息学 

分 类 号：R373.2[医药卫生—病原生物学] R511[医药卫生—基础医学]