2019—2022年长春地区柯萨奇病毒A6的流行病学与分子特征分析

Epidemiology and molecular characteristics analysis of Coxsackievirus A6 in Changchun area from 2019 to 2022

目的分析2019—2022年长春地区引起手足口病(hand,foot and mouth disease,HFMD)的柯萨奇病毒A6(Coxsackievirus A6,CV-A6)的流行情况及其VP1区的基因特征,探讨其流行规律,为优化防控策略提供参考。方法收集2019—2022年长春临床诊断HFMD病例样本878份,采用实时荧光RT-PCR方法进行肠道病毒(enterovirus,EV)核酸检测。对CV-A6阳性样本的VP1基因区进行RT-PCR扩增及测序。再利用MEGA 11构建系统发育树,并使用DNAstarV8.1.3软件分析核苷酸序列同源性和氨基酸变异。结果878份HFMD病例标本中,检出EV阳性588份,总检出率为66.97%(588/878);检出CV-A6阳性245份,CV-A6检出率为41.67%(245/588)。125份CV-A6阳性样本成功扩增并测序了VP1基因。系统发育分析表明,2019—2022年长春市测定的125株CV-A6毒株均属于D3a基因型,125株CV-A6毒株之间的核苷酸序列同源性为88.1%~100%,与原型株(Gdula)的同源性为81.2%~84.3%。其VP1区氨基酸序列出现了36个突变位点。结论2019—2022年长春地区引起HFMD的优势病原体是CV-A6,也是我国内地地区主流基因亚型D3a,但多条传播链共同循环进化。应进一步加强对CV-A6的监测。

Objective To analyse the prevalence of Coxsackievirus A6(CV-A6)causing hand,foot and mouth disease(HFMD)and the genetic characteristics of its VP1 region in Changchun area from 2019 to 2022,explore its epidemic regularity,and provide a reference for optimizing the prevention and control strategies.Methods A total of 878 samples of clinically diagnosed HFMD cases in Changchun from 2019 to 2022 were collected,and real-time RT-PCR was used for enterovirus(EV)nucleic acid detection.The VP1 gene region of CV-A6-positive samples were amplified by RT-PCR and sequenced.A phylogenetic tree was then constructed using MEGA 11,and DNAstarV8.1.3 software was used to analyze the nucleotide homology and amino acid mutations.Results Among the 878 HFMD samples,588 EV positive were detected,with the total detection rate of 66.97%(588/878);245 CV-A6 positive were detected,with the CV-A6 detection rate of 41.67%(245/588).The VP1 gene was successfully amplified and sequenced from 125 CV-A6 positive samples.Phylogenetic analysis showed that all 125 CV-A6 strains detected in Changchun from 2019 to 2022 belonged to the D3a genotype.The nucleotide sequence homology among the 125 CV-A6 strains was 88.1%to 100%,and the homology with the prototype strain(Gdula)was 81.2%to 84.3%.There were 36 site mutations in the amino acid sequence of VP1 region.Conclusion The dominant pathogen causing HFMD in Changchun from 2019 to 2022 was CV-A6,which was also the mainstream gene subtype D3a in the mainland of China.However,multiple transmission chains are circulating and evolving together,suggesting that the surveillance for CV-A6 should be further strengthened.