安徽省2020年柯萨奇病毒A组4型分离株全基因组序列分析
Whole genome sequence analysis of coxsackievirus A group 4 isolates in Anhui province in 2020
刘以诺 1葛盈露 2杨灵康 2孙永 2史永林3
作者信息
- 1. 安徽医科大学公共卫生学院,合肥 230032
- 2. 安徽省疾病预防控制中心安徽省公共卫生研究院安徽省医疗卫生重点专科病原微生物分子生物学实验室,合肥 230601
- 3. 安徽医科大学公共卫生学院,合肥 230032;安徽省疾病预防控制中心安徽省公共卫生研究院安徽省医疗卫生重点专科病原微生物分子生物学实验室,合肥 230601
- 折叠
摘要
目的 了解安徽省柯萨奇病毒A组4型(coxsackievirus A4,CV-A4)毒株全基因组序列变异及分子进化情况,为今后手足口病的病原学监测和科学防治提供理论依据.方法 采用一代测序法对2020年5株CV-A4分离株进行全基因组测序.运用MEGA11.0对5株CV-A4分离株,32株CV-A4代表株和肠道病毒A71型(Enterovirus A71,EV-A71)原型株BrCr基于VP1区构建系统进化树,对分离株以及肠道病毒A组(enterovirus A,EV-A)原型代表株基于P1、P2、P3区分别构建系统进化树;选用DNAStar进行毒株VP1区氨基酸序列比对,使用BioEdit7.2进行氨基酸置换熵分析并作氨基酸位点熵值图,使用SimPlot3.5和RDP4对CV-A4分离株和EV-A原型代表株进行重组分析,使用DnaSP6软件进行分离株和参考代表株的选择压力分析.结果 系统进化树显示:分离株属于C2亚型,与中国大陆地区流行的CV-A4毒株属于同一分支,C2亚型分支的毒株氨基酸序列同源性为97.30％-100％,分离株同原型相比,均有6个氨基酸变异位点.选择压力分析表明C2亚型的CV-A4毒株受负选择压力的影响,置换熵分析编码区氨基酸序列有25个易突变位点,占比1.14％,毒株进化主要依赖重组.重组分析表明分离株在P2、P3区域与多种EV-A原型株发生不同区段的重组,与CV-A5原型株重组区段较长,尤其在3A-3C区段,P1是相对保守的区段.结论 安徽省CV-A4在P2、P3区与其他EV-A原型株发生频繁重组事件,应对安徽省CV-A4的分子进化研究继续保持密切关注.
Abstract
Objective To understand the genome-wide sequence variation and molecular evolution of coxsackievirus A4(CV-A4)strain in Anhui province,so as to provide a theoretical basis for the pathogenic monitoring and scientific prevention and treatment of hand,foot and mouth disease in the future.Methods Five CVA4 isolates of 2020 were sequenced by first-generation sequencing method.MEGA11.0 was used to construct a phylogenetic tree based on VP1 region for 5 CV-A4 isolates,32 CV-A4 strains and Enterovirus A71(EV-A71)prototype strain BrCr,and the isolates and enterovirus A(EV-A)prototype strains based on P1,P2 and P3 regions respectively,and DNAStar was used for amino acid sequence comparison in VP1 region.BioEdit7.2 was used for amino acid displacement entropy analysis and amino acid site entropy mapping.SimPlot3.5 and RDP4 were used for recombination analysis of CV-A4 isolate and EV-A prototype representative strains,and DnaSP6 software was used for selection pressure analysis of isolates and reference representative strains.Results The phylogenetic tree showed that the isolates belonged to the C2 subtype,which belonged to the same clade as the CV-A4 strain circulating in Chinese mainland,and the amino acid sequence homology of the C2 subtype branch was 97.3％-100％,and the isolates had 6 amino acid variation sites compared with the prototype.The selection pressure analysis showed that the CV-A4 strain of the C2 subtype was affected by negative selection pressure,and there were 25 mutagenic sites in the amino acid sequence in the coding region of the displacement entropy analysis,accounting for 1.14％,and the evolution of the strain mainly depended on recombination.Recombination analysis showed that the isolates recombined with a variety of EV-A prototype strains in the P2 and P3 regions,and the recombination section with the CV-A5 prototype strain was longer,especially in the 3A-3C section,and Pl was a relatively conserved region.Conclusions CV-A4 has frequent recombination events with other EV-A prototype strains in P2 and P3,and the molecular evolution of CV-A4 in Anhui should continue to be closely monitored.
关键词
柯萨奇病毒A组4型/全基因组/系统进化分析Key words
Coxsackievirus A4(CV-A4)/Complete genome sequence/Phylogenetic analysis引用本文复制引用
基金项目
安徽省自然科学基金(1708085QH186)
出版年
2024
NETL
NSTL
万方数据