摘要
目的了解柯萨奇病毒A组10型(coxsackievirus A10,CV-A10)总体的分子流行病学及时空进化规律。方法对美国国立生物技术信息中心(National Center for Biotechnology Information,NCBI)中2020年4月10日前提交的所有完整VP1序列进行分析。采用最大似然法(maximum likelihood,ML)构建系统进化树,采用贝叶斯因子法(Bayes factor,BF)分析平均碱基替换速率、最早共同祖先和起源进化,采用贝叶斯天际线图(Bayesian skyline plot,BSP)方法分析群体动态历史,采用EasyCodeML 1.2软件对不同序列集进行选择压力分析。结果1950—2018年CV-A10分为A~F共6个基因型,其中C基因型分为C1~C3基因亚型。CV-A10于1865[95%的最大密度置信区间(95%highest probability density interval,95%HPD interval):1818.82—1908.34]年起源于美国,约在1990年传播至中国大陆,2010—2018年在世界范围广泛传播。在2009年和2014年,CV-A10出现两次显著的种群扩张,且2018年后有效种群大小为98.79,显著高于以前。CV-A10每年的平均碱基替换速率为4.66×10^(-3)(95%HPD interval:3.97×10^(-3)~5.35×10^(-3))。2008年后,我国大陆的优势株为C3基因亚型毒株,该亚型毒株的起源可追溯到2006.19(95%HPD interval:2005.32—2006.99)年。筛选到6个位于VP1区的正选择压力位点,分别为140E、141E、220T、239E、282A和284T。结论本研究中CV-A10分为A~F型,C基因型分为C1~C3基因亚型。CV-A10起源于1865年的美国,曾出现两次种群扩张。筛选到的220T、239E、282A和284T可能与病毒进入及中和表位有关。
Objective To understand the molecular epidemiology and spatio-temporal evolution characteristics of coxsackievirus A10(CV-A10).Methods All complete VP1 sequences submitted on National Center for Biotechnology Information(NCBI)before April 10,2020 were analyzed.Maximum likelihood method(ML)was used to construct phylogenetic tree.The Bayesian factor method(BF)was used to analyze the average substitution rate of bases,the most recent common ancestor and origin evolution.The Bayesian skyline plot method(BSP)was used to analyze population dynamic history.And the selective pressure analysis by EasyCodeML 1.2 software was done for different data sets.Results The results showed that the CV-A10 strains in 1950—2018 were clustered into six genotypes:A—F,and genotype C was further divided into sub-genotypes C1—C3.CV-A10 probably originated from the United States in 1865(95%highest probability density interval(HPD)interval:1818.82—1908.34),spread to mainland China in 1990,and circulated worldwide since 2010.There were two significant increases in the population size of CV-A10 with the peak in 2009 and 2014,respectively.In 2018,the effective population size to 98.79,which was significantly higher than that before the population expansion occurred.The mean rate of base substitution of CV-A10 were 4.66×10^(-3)(95%HPD interval:3.97×10^(-3)—5.35×10^(-3))per year.The most recent common ancestor(tMRCA)of sub-genotype C3,which has become the major epidemic strain in mainland China since 2008,dated back to 2006.19(95%HPD interval:2005.32-2006.99).A total of 6 positive pressure sites in VP1 were selected,including 140 E,141 E,220 T,239 E,282 Aand 284 T.Conclusions CV-A10 can be divided into A—F genotypes and C subgenotype into C1—C3 sub-genotypes.CV-A10 originated in the United States in 1865 and has undergone two population expansions.The 220 T,239 E,282 A,and 284 Tare screened for possible viral entry and neutralization epitopes.
作者
霍雅倩
高帆
刘佩
宋丽芳
杨靖寰
张佳璐
毛群颖
卞莲莲
李秀玲
HUO Ya-qian;GAO Fan;LIU Pei;SONG Li-fang;YANG Jing-huan;ZHANG Jia-lu;MAO Qun-ying;BIAN Lian-lian;LI Xiu-ling(Shanghai Institute of Biological Products Co.,Ltd,Shanghai 200051,China;Hepatitis Virus Vaccine Room of National Institutes for Food and Drug Control,Beijing102629,China;不详)
出处
《中国病毒病杂志》
CAS
2021年第4期275-283,共9页
Chinese Journal of Viral Diseases
基金
国家科技重大专项(2018X09737-011)。
