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山东大学学报 (医学版) ›› 2025, Vol. 63 ›› Issue (9): 92-101.doi: 10.6040/j.issn.1671-7554.0.2024.1149

• 临床医学 • 上一篇    

2021年济宁市柯萨奇病毒A组6型分离株全基因组特征分析

王珊1,2,3,刘伟1,3,冯强4,范莹莹1,3,刘海霞1,3,段延华1,温红玲2,焦伯延1,3   

  1. 1.济宁市疾病预防控制中心, 山东 济宁 272008;2.山东大学公共卫生学院, 山东 济南 250100;3.济宁市传染病预防控制重点实验室, 山东 济宁 272008;4.济宁市任城区疾病预防控制中心, 山东 济宁 272103
  • 发布日期:2025-09-08
  • 通讯作者: 温红玲. E-mail:wenhongling@sdu.edu.cn焦伯延. E-mail:j198319831983@126.com
  • 基金资助:
    山东省医药卫生科技发展计划项目(202112060725);山东省学校卫生协会科研课题(SDWS2022046)

Whole genome characterization analysis of Coxsackievirus A6 in Jining in 2021

WANG Shan1,2,3, LIU Wei1,3, FENG Qiang4, FAN Yingying1,3, LIU Haixia1,3, DUAN Yanhua1, WEN Hongling2, JIAO Boyan1,3   

  1. 1.Jining Center for Disease Control and Prevention, Jining 272008, Shandong, China;
    2. School of Public Health, Shandong University, Jinan 250100, Shandong, China;
    3. Jining Key Laboratory of Infectious Disease Control and Prevention, Jining 272008, Shandong, China;
    4. Jining Rencheng Center for Disease Control and Prevention, Jining 272103, Shandong, China
  • Published:2025-09-08

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摘要： 目的 分析2021年济宁市柯萨奇病毒A组6型(Coxsackievirus A6, CVA6)流行特点和全基因组特征,为手足口病的防控提供依据。 方法 采用反转录实时荧光定量PCR(reverse transcription quantitative real-time PCR,RT-qPCR)法对2021年济宁市11县市区采集的手足口病病例样本进行CVA6核酸检测;将CVA6阳性样本接种到人横纹肌瘤细胞进行病毒的细胞培养,提取病毒核酸,并采用二代测序技术进行全基因组测序;采用MEGA 7.0.14、RNAfold、NetPhos 3.1、NetNGlyc 1.0和GPS Lipid生物信息学软件进行相似性、构建内部核糖体进入位点(internal ribosome entrysite, IRES)二级结构、磷酸化位点、糖基化位点和脂酰化位点分析。 结果 核酸检测结果显示,2021年济宁市手足口病肠道病毒阳性病例中CVA6占比为35.79%(97/271)。全基因组测序结果显示,3株CVA6与原型株Gdula的核苷酸同源性为80.69%~80.95%,多聚蛋白氨基酸同源性为94.83%~94.92%。生物信息学分析结果显示,在进化树上,3株CVA6均位于D3a进化分支,但位于不同的进化簇。与原型株Gdula相比,5’UTR的IRES区共发生了7处核苷酸变异,VP1抗原表位发生了Q98L、G160S变异,VP1受体结合位点发生了S194T变异,3D聚合酶活性位点发生了T308S、L342S和K346R变异。此外编码蛋白的磷酸化位点、糖基化位点和脂酰化位点均发生多处位点的变异。 结论 2021年济宁市手足口病病例中CVA6是主要病原体,向适应宿主的方向进化,应加强对CVA6的监测和防控。

关键词: 手足口病, 肠道病毒, 柯萨奇病毒A组6型, 全基因组分析

Abstract: Objective To analyze the epidemiological characteristics and whole-genome features of Coxsackievirus A6(CVA6)in Jining City in 2021, providing a basis for the prevention and control of hand, foot, and mouth disease(HFMD). Methods Reverse transcription quantitative real-time PCR(RT-qPCR)was used to detect CVA6 nucleic acid in HFMD case samples collected from 11 counties and districts in Jining City in 2021. CVA6-positive samples were inoculated into human rhabdomyosarcoma cells for viral culture, and viral nucleic acid was extracted for whole-genome sequencing using next-generation sequencing technology. Bioinformatics analyses, including sequence similarity analysis, internal ribosome entry site(IRES)secondary structure modeling, phosphorylation site analysis, glycosylation site analysis, and lipidation site analysis, were conducted using MEGA 7.0.14, RNAfold, NetPhos 3.1, NetNGlyc 1.0, and GPS Lipid software. Results Nucleic acid testing showed that the positive rate of CVA6 among the confirmed HFMD cases in Jining City in 2021 was 35.79%(97/271). Whole-genome sequencing results revealed that three CVA6 strains exhibited nucleotide homology of 80.69%-80.95% and polyprotein amino acid homology of 94.83%-94.92% with the prototype strain Gdula. Bioinformatics analysis showed that all three CVA6 strains belonged to the D3a evolutionary branch but were located in different evolutionary clusters. Compared to the Gdula prototype strain, seven nucleotide mutations were observed in the 5'UTR IRES region, Q98L and G160S mutations occurred in the VP1 antigenic epitope, an S194T mutation was found in the VP1 receptor-binding site, and T308S, L342S, and K346R mutations were identified in the 3D polymerase active site. Additionally, multiple variations were observed in phosphorylation, glycosylation, and lipidation sites of the encoded proteins. Conclusion CVA6 was the predominant pathogen in HFMD cases in Jining City in 2021. It was evolving in the direction of adapting to the host. The monitoring and prevention efforts against CVA6 should be strengthened.

Key words: Hand, foot and mouth disease, Enterovirus, Coxsackievirus A6, Whole genome analysis

中图分类号: 

  • R183.4
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