安徽省2017-2018年手足口病柯萨奇病毒A6型基因进化特征分析  

Genetic Characterization of Coxsackievirus A6 Associated with Hand,Foot,and Mouth Disease in Anhui Province,China,2017–2018

作　　者：史永林[1] 葛盈露 马婉婉[1] 陈芳[1] 陈国平[1] 孙永[1] 苏斌[1] SHI Yonglin;GE Yinglu;MA Wanwan;CHEN Fang;CHEN Guoping;SUN Yong;SU Bin(Anhui Provincial Center for Disease Control and Prevention,Public Health Research Institute of Anhui Province Key Laboratory for Medical and Health of the 13th Five-year Plan in Anhui Province,Hefei 230601,China)

机构地区：[1]安徽省疾病预防控制中心安徽省公共卫生研究院,安徽省“十三五”医疗卫生重点实验室,合肥230601

出　　处：《病毒学报》2021年第6期1326-1332,共7页Chinese Journal of Virology

基　　金：安徽省自然科学基金项目(项目号:1708085QH186),题目:TLR基因多态性与EVA71导致的手足口病重症的关联性研究。

摘　　要：人肠道病毒A组71型(Enterovirus A71,EV-A71)和柯萨奇病毒A组16型(Coxsackievirus A16,CV-A16)是引起手足口病(Hand,foot,and mouth disease,HFMD)的主要病原体。近年来非EV-A71和非CV-A16的其他肠道病毒(Enterovirus,EV)已成为HFMD流行或暴发疫情的优势病原体。安徽省HFMD监测数据显示,2017-2018年HFMD样本非EV-A71和非CV-A16其他EV核酸阳性率超过50%,其中大部分为柯萨奇病毒A组6型(Coxsackievirus A6,CV-A6)。为了解安徽省2017-2018年HFMD其他肠道病毒构成和CV-A6基因进化特征,本研究收集2017-2018年HFMD咽拭子EV核酸阳性标本,采用人横纹肌肉瘤(RD)细胞进行病毒分离培养,对分离到的CV-A6毒株VP1全长序列基因扩增及核苷酸序列测定。从NCBI GenBank数据库下载CV-A6原型株和代表性毒株基因参考序列,运用生物软件MEGA 6.0构建VP1基因序列系统进化树,分析其基因遗传特征。结果显示,安徽省2017-2018年HFMD实验室确诊病例其他EV占66.1%,CV-A16占23.5%,EV-A71占10.4%。52株CV-A6毒株均为D3a基因亚型,其VP1区核苷酸序列间相似度为93.7%~100%,编码的氨基酸序列相似度为98.3%~100%;与CV-A6 Gdula原型株核苷酸相似度为78%~82.3%,氨基酸相似度为94.6%~96.3%。VP1区15个氨基酸位点有变异,氨基酸位点Q98L和G160S的变异发生率为100%。其他EV已成为安徽省引起HFMD流行的重要病原体,D3基因型CV-A6为优势流行毒株。持续加强其他EV的病原学监测与分析,对安徽省HFMD防控策略制定与疫情处置具有重要意义。Enterovirus A71(EV-A71)and coxsackievirus A16(CV-A16)are traditionally considered the main pathogens of hand,foot,and mouth disease(HFMD). However,in recent years,other enteroviruses(EVs)have become dominant pathogens in HFMD epidemics or outbreaks. HFMD monitoring data from Anhui Province,China,showed that the rate of"other EVs"in HFMD samples(based on nucleic acid sequences)from 2017 to 2018 was >50%,most of which were coxsackievirus A6(CV - A6). To understand the prevalence of other EVs and the evolutionary characteristics of CV -A6 isolates in HFMD in Anhui Province,China,we collected EV nucleic acid-positive specimens from throat swabs of HFMD patients in 2017–2018,and used human rhabdomyosarcoma cells for viral isolation and culture. The full-length VP1 gene of CV -A6 strains was amplified and sequenced. Reference gene sequences for the CV - A6 prototype and representative strains were downloaded from the NCBI GenBank database,and a phylogenetic tree based on VP1 sequences was constructed using MEGA 6.0 software. Results showed that"other EVs"accounted for 66.1%,CV-A16 for 23.5%,and EV -A71 for 10.4% of laboratory-confirmed HFMD cases in Anhui Province,China,during2017-2018. All 52 of the CV-A6 strains belonged to the D3 a sub-genotype. Among these strains,the nucleotide sequence similarity of the VP1 region was 93.7%–100%,and the amino acid sequence similarity was 98.3%–100%. Compared with the CV-A6 prototype strain,the nucleotide similarity of the VP1 region was 78.0% –82.3% and the amino acid similarity was 94.6% – 96.3%. Fifteen amino acid sites in the VP1 region were mutated,and the rate of mutations Q98 L and G160 S was 100%."Other EVs"have become important pathogens causing HFMD epidemics in Anhui Province,China. D3-genotype CV-A6 is the predominant strain of this virus causing HFMD epidemics in the region. It is of great significance to continuously strengthen etiological monitoring and analysis of other EVs for the formulation of HFMD prevention and control strategies and epidemic disposa

关 键 词：手足口病(HFMD) 人肠道病毒 柯萨奇病毒A6型(CV-A6) D基因型 进化分析 

分 类 号：R373.2[医药卫生—病原生物学]