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为了解南京市2018-2022年引起手足口病的重要病原体柯萨奇病毒A组6型(Coxsackievirus A6,CVA6)的基因特征及重组规律,为由CVA6引起的手足口病疫情防控提供一定的科学数据。收集2018-2022年南京市各区疾控中心上送的手足口病监测标本,用实时荧光定量PCR检测肠道病毒并分型,CVA6阳性标本通过一步法RTPCR对肠道病毒结构蛋白VP1区(915bp)和非结构蛋白3D区(812bp)进行扩增并测定序列,选取两个片段均测定成功的CVA6进行生物信息学分析。2018-2022年共收集疑似手足口标本2609份,肠道病毒阳性标本数1433份,阳性率54.93%(1433/2609)。肠道病毒阳性病例中,男女比例1.40∶1,0~3岁为高发年龄段,占肠道病毒总阳性数的61.34%(879/1433)。受新冠疫情影响,手足口病肠道病毒阳性病例的季节性在各个年份有较大差异。121株南京CVA6 VP1区核苷酸相似性为89.5%~100.0%,氨基酸相似性为97.0%~100.0%。基于VP1区序列系统发育分析表明,2018-2022年南京CVA6株均属于D3亚基因型,120株属于D3a分支,2019年仅有一株属于D3b分支。非结构蛋白3D区序列的分子系统发育分析显示,2018-2022年南京CVA6株3D型别以重组形式(Recombinant form,RF)A为主,2022年出现了与本研究的其他南京株及常见的各谱系代表株遗传距离较远的新谱系。2018-2022年南京市引起手足口病的CVA6以D3a基因亚型为主,3D型别以RF-A为主,2022年可能出现了新的重组型别。
Abstract:This study aims to analyze the genetic characteristics and recombination of Coxsackievirus A6(CVA6), an important pathogen causing hand, foot, and mouth disease(HFMD) in Nanjing, China from 2018 to 2022, and to provide scientific data for the prevention and control of HFMD epidemics caused by CVA6. HFMD surveillance specimens were collected from various district Centers for Disease Control and Prevention(CDCs) in Nanjing, China between 2018 and 2022. Enterovirus detection and typing were performed using real-time fluorescence quantitative PCR. CVA6-positive specimens underwent one-step RTPCR amplification and sequencing of the structural protein VP1 region(915 bp) and the nonstructural protein 3D region(812 bp). CVA6 strains with successfully sequenced both fragments were selected for bioinformatics analysis. A total of 2609 suspected HFMD samples were collected from 2018 to 2022, and 1433 samples were positive for enterovirus, with a positive rate of 54.93%(1433/2609). Among the enterovirus positive cases, the ratio of male to female was 1.40:1, and the age group under 3 years old is the high-incidence age range, accounting for 61.34%(879/1433) of the total enterovirus positive cases. Due to the influence of COVID-19, the seasonality of HFMD enterovirus positive cases varies greatly in different years. The nucleotide identity of the VP1 region of the 121 CVA6 strains ranged from 89.5% to 100.0%, and amino acid identity ranged from 97.0% to 100.0%. Phylogenetic analysis of VP1 sequences revealed that all CVA6 strains from Nanjing during 2018-2022 belonged to subgenotype D3 within genotype D, with 120 strains clustering in the D3a branch and only one strain from 2019 clustering in the D3b branch. Molecular phylogenetic analysis of the 3D region sequences of non-structural proteins indicated that recombinant form(RF) A was the predominant genotype in the 3D region of CVA6 strains during this period. In 2022, a new lineage emerged that had a relatively large genetic distance from other Nanjing strains in this study and the representative strains of common lineages.Genotype D3a was the main genotype of CVA6 causing HFMD in Nanjing, China from 2018 to 2022, and RFA was the main genotype in the 3D region. A new recombinant type might have emerged in 2022.
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基本信息:
DOI:10.13242/j.cnki.bingduxuebao.240198
中图分类号:R373.23
引用信息:
[1]梅唐林,董晓庆,乔梦凯等.2018-2022年南京市引起手足口病的柯萨奇病毒A组6型基因特征分析[J].病毒学报,2025,41(02):326-333.DOI:10.13242/j.cnki.bingduxuebao.240198.
基金信息:
南京市科技计划项目(项目号:2021-11005),题目:南京市重大传染病早期预警及精准防控关键技术研究~~