您的位置:山东大学 -> 科技期刊社 -> 《山东大学学报(医学版)》

山东大学学报 (医学版) ›› 2021, Vol. 59 ›› Issue (5): 60-67.doi: 10.6040/j.issn.1671-7554.0.2021.0278

• 医学病毒的基础与临床研究进展专题 • 上一篇    下一篇

济南市2012~2017年手足口病4种优势肠道病毒阳性及VP1基因型分布

关恒云,王春荣,刘岚铮*(),赵怀龙,白爱英,姜慧钰,董华,李娜,单晓英,成洪旗   

  1. 济南市疾病预防控制中心细菌性疾病检验所, 山东 济南 250021
  • 收稿日期:2021-03-12 出版日期:2021-05-10 发布日期:2021-06-01
  • 通讯作者: 刘岚铮 E-mail:jncdcllz@jn.shangdong.cn
  • 基金资助:
    山东省医药卫生科技发展计划(2016WS0116)

Positive distribution of four dominant enteroviruses associated with hand, foot and mouth disease and VP1 genotypes in Jinan, China, 2012-2017

Hengyun GUAN,Chunrong WANG,Lanzheng LIU*(),Huailong ZHAO,Aiying BAI,Huiyu JIANG,Hua DONG,Na LI,Xiaoying SHAN,Hongqi CHENG   

  1. Bacterial Disease Inspection Laboratory, Jinan Center for Disease Control and Prevention, Jinan 250021, Shandong, China
  • Received:2021-03-12 Online:2021-05-10 Published:2021-06-01
  • Contact: Lanzheng LIU E-mail:jncdcllz@jn.shangdong.cn

摘要:

目的: 阐明济南市手足口病优势肠道病毒感染类型及VP1基因型分布。方法: 采用实时荧光定量逆转录-聚合酶链反应(RT-PCR)对2012~2017年济南市4929份手足口病病例标本进行肠道病毒71型(EV-A71)、柯萨奇病毒A组16型(CV-A16)、柯萨奇病毒A组6型(CV-A6)和柯萨奇病毒A组10型(CV-A10)进行鉴定。按照不同年份回顾性收集手足口病病毒分离株65株,包括17株EV-A71、16株CV-A16、20株CV-A6和12株CV-A10。采用RT-PCR方法扩增肠道病毒VP1特异性基因并进行核苷酸序列测定;获得的目的基因序列进行核苷酸同源性分析并构建系统进化树。结果: 济南市手足口病优势肠道病毒类型为CV-A16(28.3%)、EV-A71(27.3%)、CV-A6(17.0%)、CV-A10(3.0%)。4种优势肠道病毒VP1基因目的片段长度分别为891 bp、1 015 bp、1 110 bp和993 bp。济南市EV-A71病毒株间核苷酸序列同源性为93.0%~98.1%,CV-A16为87.4%~100.0%,CV-A6为87.6%~99.7%,CV-A10为95.8%~99.4%。系统进化树分析显示,济南市EV-A71均为C4a亚型;CV-A16存在B1b型和B1a型两种基因亚型;CV-A6在系统进化树的C簇、E簇和F簇均有分布;CV-A10全部位于进化树E簇。结论: CV-A16、EV-A71、CV-A6和CV-A10为济南市2012~2017年手足口病的优势肠道病毒;长期动态监测肠道病毒VP1基因型分布,对于提高手足口病预警敏感性具有重要的公共卫生意义。

关键词: 手足口病, 肠道病毒, VP1基因, 系统进化分析

Abstract:

Objective: To elucidate the dominant enteroviruses associated with hand, foot and mouth disease (HFMD) and the distributions of VP1 genotypes in Jinan City. Methods: Real-time quantitative reverse transcription-polymerase chain reaction (RT-PCR) was used to detect enterovirus A71 (EV-A71), coxsackievirus A16 (CV-A16), coxsackievirus A6 (CV-A6) and coxsackievirus A10 (CV-A10) in 4929 HFMD specimens from 2012 to 2017 in Jinan. According to different years, 65 virus isolates of HFMD were retrospectively collected, including 17 strains of EV-A71, 16 of CV-A16, 20 of CV-A6 and 12 of CV-A10. The VP1 gene of enteroviruses was amplified by RT-PCR and the nucleotide sequencing was performed. Nucleotide homology analyses were performed and phylogenetic trees were constructed on the VP1 gene. Results: The dominant enteroviruses of HFMD were CV-A16 (28.3%), EV-A71(27.3%), CV-A6(17.0%) and CV-A10(3.0%) in Jinan. The lengths of VP1 gene on CV-A16, EV-A71, CV-A6 and CV-A10 amplified by RT-PCR were 891 bp, 1 015 bp, 1 110 bp and 993 bp, respectively. The nucleotide homology was 93.0%-98.1% for EV-A71 strains, 87.4%-100.0% for CV-A16 strains, 87.6%-99.7% for CV-A6 strains, and 95.8%-99.4% for CV-A10 strains. The phylogenetic trees showed that EV-A71 strains belonged to C4a genotype in Jinan, CV-A16 strains had two genetic subtypes (B1b and B1a); CV-A6 strains located in clusters C, E and F, and CV-A10 strains located in cluster E. Conclusion: The dominant enteroviruses of HFMD are CV-A16, EV-A71, CV-A6 and CV-A10 from 2012 to 2017 in Jinan. The long-term dynamic monitoring of the distribution of VP1 genotypes is of great public health significance for improving the early warning sensitivity for HFMD.

Key words: Hand, foot and mouth disease, Enterovirus, VP1 gene, Phylogenetic analysis

中图分类号: 

  • R115

表1

济南市2012~2017年手足口病4种优势肠道病毒阳性检出分布"

年份 病例数 性别 年龄(中位数)(岁) 阳性检出数[n(%)] χ2 P
EV-A71 CV-A16 CV-A6 CV-A10
2012 859 515 344 0.3~44(3.0) 203(23.6) 368(42.8) 15(1.7) 39(4.5) 631.493a < 0.001
2013 848 489 359 0.2~21(3.0) 289(34.1) 148(17.5) 164(19.3) 12(1.4) 306.820a < 0.001
2014 935 545 390 0.3~23(3.0) 223(23.9) 357(38.2) 125(13.4) 62(6.6) 325.238a < 0.001
2015 756 453 303 0.3~30(3.1) 219(29.0) 82(10.8) 281(37.2) 5(0.7) 401.888a < 0.001
2016 741 433 308 0.1~30(3.0) 88(11.9) 372(50.2) 66(8.9) 30(4.0) 656.183a < 0.001
2017 790 467 323 0.1~30(3.0) 326(41.3) 66(8.4) 188(23.8) 2(0.3) 516.410a < 0.001

图1

济南市手足口病EV-A71 VP1基因核苷酸序列同源性分析(A)及系统进化树构建(B) ▲代表济南市EV-A71株。"

图2

济南市手足口病CV-A16 VP1基因核苷酸序列同源性分析(A)及系统进化树构建(B) ●代表济南市CV-A16株。"

图3

济南市手足口病CV-A6 VP1基因核苷酸序列同源性分析(A)及系统进化树构建(B) ●代表济南市CV-A6株。"

图4

济南市手足口病CV-A10 VP1基因核苷酸序列同源性分析(A)及系统进化树构建(B) ●代表济南市CV-A10株。"

1 关恒云, 王春荣, 刘岚铮, 等. 济南市2012~2017年手足口病肠道病毒谱变化及流行特征[J]. 山东大学学报(医学版), 2019, 57 (11): 90- 97.
GUAN Hengyun , WANG Chunrong , LIU Lanzheng , et al. Changes of enterovirus spectrum and epidemiological characteristics of hand, foot and mouth disease in Jinan, China, 2012-2017[J]. Journal of Shandong University (Health Science), 2019, 57 (11): 90- 97.
2 李晓君, 唐海丰, 何鑫, 等. 2015-2018年上海市普陀区手足口病病原谱及柯萨奇病毒基因特征分析[J]. 国际病毒学杂志, 2020, 27 (1): 57- 60.
doi: 10.3760/cma.j.issn.1673-4092.2020.01.014
LI Xiaojun , TANG Haifeng , HE Xin , et al. Pathogen spectrum of hand, foot, and mouth disease and genetic characteristics of the VP1 gene of coxsackievirus A6 in Putuo district of Shanghai, 2015-2018[J]. International Journal of Virology, 2020, 27 (1): 57- 60.
doi: 10.3760/cma.j.issn.1673-4092.2020.01.014
3 李婕, 马江涛, 刘俐, 等. 2016-2017年宁夏手足口病的病原构成及流行的EV-A71和CV-A16基因特征分析[J]. 中华实验和临床病毒学杂志, 2019, 33 (1): 10- 14.
doi: 10.3760/cma.j.issn.1003-9279.2019.01.003
LI Jie , MA Jiangtao , LIU Li , et al. Pathogenic composition of hand, foot and mouth disease and enterovirus-A71 and coxsackievirus-A16 genetic characteristics analysis in Ningxia, 2016-2017[J]. Chinese Journal of Experimental and Clinical Virology, 2019, 33 (1): 10- 14.
doi: 10.3760/cma.j.issn.1003-9279.2019.01.003
4 Oberste MS , Maher K , Pallansch DR , et a1 . Typing of human enteroviruses by partial sequencing of VP1[J]. J Clin Microbiol, 1999, 37 (5): 1288- 1293.
doi: 10.1128/JCM.37.5.1288-1293.1999
5 中华人民共和国卫生部.手足口病预防控制指南(2009版) [EB/OL]. (2021-03-12)[2009-06-04]. http://www.gov.cn/gzdt/2009-06/04/content_1332078.htm.
6 关恒云, 王春荣, 吕燕, 等. 2012年济南市手足口病病原学及流行特征[J]. 山东大学学报(医学版), 2013, 51 (10): 101- 104.
GUAN Hengyun , WANG Chunrong , LYU Yan , et al. Etiology and epidemiological characteristics of hand-foot-mouth disease in Jinan in 2012[J]. Journal of Shandong University (Health Science), 2013, 51 (10): 101- 104.
7 Kroneman A , Vennema H , Deforche K , et al. An automated genotyping tool for enteroviruses and noroviruses[J]. J Clin Virol, 2011, 51 (2): 121- 125.
doi: 10.1016/j.jcv.2011.03.006
8 Oberste MS , Maher K , Kilpatrick DR , et a1 . Molecular evolution of the human enteroviruses: correlation of serotype with VP1 sequence and application to picornavirus classification[J]. J Virol, 1999, 73 (3): 1941- 1948.
doi: 10.1128/JVI.73.3.1941-1948.1999
9 Brown BA , Oberste MS , Yamaoka K , et a1 . Outbreak of hand-foot-and-mouth disease by enterovirus 71 strains isolated from 1970 to 1998[J]. J Viml, 1999, 73 (12): 9969- 9975.
10 Hassel C , Mirand A , Farkas A , et a1 . Phylogeography of coxsackievirus A16 reveals global transmission pathways and recent emergence and spread of a recombinant genogroup[J]. J Virol, 2017, 91 (18): e00630- 17.
doi: 10.1128/JVI.00630-17
11 Kataoka C , Suzuki T , Kotani O , et al. The role of VP1 amino acid residue 145 of enterovirus 71 in viral fitness and pathogenesis in a cynomolgus monkey model[J]. PLoS Pathog, 2015, 11 (7): e1005033.
doi: 10.1371/journal.ppat.1005033
12 van der Sanden S , Koopmans M , Uslu G , er al . Epidemiology of enterovirus 71 in the Netherlands, 1963 to 2008[J]. J Clin Microbiol, 2009, 47 (9): 2826- 2833.
doi: 10.1128/JCM.00507-09
13 Zhang B , Wu X , Huang K , et al. The variations of VP1 protein might be associated with nervous system symptoms caused by enterovirus 71 infection[J]. BMC Infect Dis, 2014, 14, 243.
doi: 10.1186/1471-2334-14-243
14 王联君, 李艳宇. 2017年北京市东城区EV-A71和CV-A16分离株VP1基因序列特征分析[J]. 中华实验和临床病毒学杂志, 2018, 32 (5): 505- 509.
doi: 10.3760/cma.j.issn.1003-9279.2018.05.012
WANG Lianjun , LI Yanyu . Analysis of the VP1 genetic sequence characteristics of EV-A71 and CV-A16 in Dongcheng District, Beijing, 2017[J]. Chinese Journal of Experimental and Clinical Virology, 2018, 32 (5): 505- 509.
doi: 10.3760/cma.j.issn.1003-9279.2018.05.012
15 范丽霞, 王卫军, 巴卓玛, 等. 青海省2016-2017年人肠道病毒A组71型基因特征[J]. 中华实验和临床病毒学杂志, 2018, 32 (5): 501- 504.
doi: 10.3760/cma.j.issn.1003-9279.2018.05.011
FAN Lixia , WANG Weijun , BA Zhuoma , et al. Genetic characteristics of human enterovirus A type 71 in Qinghai Province during 2016-2017[J]. Chinese Journal of Experimental and Clinical Virology, 2018, 32 (5): 501- 504.
doi: 10.3760/cma.j.issn.1003-9279.2018.05.011
16 Duong V , Mey C , Eloit M , et al. Molecular epidemiology of human enterovirus 71 at the origin of an epidemic of fatal hand, foot and mouth disease cases in Cambodia[J]. Emerg Microbes Infect, 2016, 5 (9): e104.
doi: 10.1038/emi.2016.101
17 Perera D , Yusof MA , Podin Y , et a1 . Molecular phylogeny of modern coxsackievirus A16[J]. Arch Viml, 2007, 152 (6): 1201- 1208.
18 Zhang Y , Wang D , Yan D , et a1 . Molecular evidence of persistent epidemic and evolution of subgenotype B1 coxsackievirus A16-associated hand, foot, and mouth disease in China[J]. J Clin Microbio1, 2010, 48 (2): 619- 622.
doi: 10.1128/JCM.02338-09
19 Han Z , Song Y , Xiao J , et al. Genomic epidemiology of coxsackievirus A16 in mainland of China, 2000-18[J]. Virus Evol, 2020, 6 (2): veaa084.
doi: 10.1093/ve/veaa084
20 张宝敏, 陈海云, 檀晓娟, 等. 海南省2010年柯萨奇病毒A组16型VP1区基因特征分析[J]. 中华实验和临床病毒学杂志, 2014, 28 (3): 173- 175.
doi: 10.3760/cma.j.issn.1003-9279.2014.03.005
ZHANG Baomin , CHEN Haiyun , TAN Xiaojuan , et al. Genetic characteristics of coxsackievirus A 16 VP1 in Hainan Province of China in 2010[J]. Chinese Journal of Experimental and Clinical Virology, 2014, 28 (3): 173- 175.
doi: 10.3760/cma.j.issn.1003-9279.2014.03.005
21 Noisumdaeng P , Korkusol A , Prasertsopon J , et al. Longitudinal study on enterovirus A71 and coxsackievirus A16 genotype/subgenotype replacements in hand, foot and mouth disease patients in Thailand, 2000-2017[J]. Int J Infect Dis, 2019, 80, 84- 91.
doi: 10.1016/j.ijid.2018.12.020
22 Min N , Ong YHB , Han AX , et al. An epidemiological surveillance of hand foot and mouth disease in paediatric patients and in community: a Singapore retrospective cohort study, 2013-2018[J]. PLoS Negl Trop Dis, 2021, 15 (2): e0008885.
doi: 10.1371/journal.pntd.0008885
23 Wang H , Yu W , Xu T , et al. Molecular characteristic analysis for the VP1 region of coxsackievirus A6 strains isolated in Jiujiang area, China, from 2012 to 2013[J]. Medicine (Baltimore), 2019, 98 (14): e15077.
doi: 10.1097/MD.0000000000015077
24 崔鹏, 李昱, 周崇臣, 等. 不同肠道病毒引起的555例手足口病门诊病例临床分析[J]. 中华儿科杂志, 2019, 57 (6): 445- 451.
doi: 10.3760/cma.j.issn.0578-1310.2019.06.009
CUI Peng , LI Yu , ZHOU Chongchen , et al. Clinical analysis of 555 outpatients with hand, foot and mouth diseases caused by different enteroviruses[J]. Chinese Journal of Pediatrics, 2019, 57 (6): 445- 451.
doi: 10.3760/cma.j.issn.0578-1310.2019.06.009
25 Broccolo F , Drago F , Ciccarese G , et al. Severe atypical hand-foot-and-mouth disease in adults due to coxsackievirus A6: clinical presentation and phylogenesis of CV-A6 strains[J]. J Clin Virol, 2019, 110, 1- 6.
doi: 10.1016/j.jcv.2018.11.003
[1] 白永娟,庄志超,郝树彬,王莉鸿,李纯,鲁燕,赵丽,王志玉,温红玲. 肠道病毒71型3D重组病毒的拯救[J]. 山东大学学报(医学版), 2017, 55(8): 7-12.
[2] 邓轲,刘毅,盖中涛. 间充质干细胞对肠道病毒71型的易感性及miRNA的差异表达[J]. 山东大学学报(医学版), 2017, 55(3): 25-31.
[3] 刘红杨,肖金环,王凡,杨光,刘洪庆. 集中度和圆形分布法分析山东省2008~2014年手足口病季节性特征[J]. 山东大学学报(医学版), 2016, 54(12): 77-81.
[4] 马英伟, 孙乐乐, 李静, 乔乔, 庄志超, 赵丽, 于学杰, 王志玉, 温红玲, 孙妍琳. 肠道病毒71型微复制子的构建[J]. 山东大学学报(医学版), 2015, 53(9): 35-40.
[5] 岑治宏, 郭予洁, 伍伟锋, 李丽萍, 周秋曦. 病毒性心肌炎小鼠调节性B细胞的变化[J]. 山东大学学报(医学版), 2015, 53(5): 31-35.
[6] 李静, 乔乔, 孙乐乐, 马英伟, 庄志超, 赵丽, 王志玉, 温红玲. 肠道病毒71型3CD蛋白对细胞的损伤作用[J]. 山东大学学报(医学版), 2015, 53(12): 16-19.
[7] 李敏, 段坤, 赵瑞霞. 2010-2013年济南市历城区414例手足口病病例分析[J]. 山东大学学报(医学版), 2014, 52(9): 54-57.
[8] 陶泽新, 杨静, 王海岩, 林小娟, 王素婷, 宋立志, 徐爱强. 2011年济南市某污水河中肠道病毒的分离鉴定与序列分析[J]. 山东大学学报(医学版), 2014, 52(11): 97-100.
[9] 关恒云, 王春荣, 吕燕,张雯,杨国樑,刘岚铮. 2012年济南市手足口病病原学及流行特征[J]. 山东大学学报(医学版), 2013, 51(10): 101-104.
[10] 袁晓晶1,温红玲1,高峰2,许洪芝1,司鲁莹1,王东旭1,宋艳艳1,赵丽1,王志玉1. 肠道病毒71型基因组5′非编码区序列分析[J]. 山东大学学报(医学版), 2012, 50(9): 127-.
[11] 宋楠楠1,张颖2,李鹏1,岳盈盈1,李志会1,盖中涛2,孟红1. EV71临床分离株BALB/c小鼠致病特点分析[J]. 山东大学学报(医学版), 2012, 50(8): 35-.
[12] 王东旭1,温红玲1,董华1,孙成玺1,司鲁莹1,袁晓晶1,褚福禄1,赵丽1,王志玉1, 2. 不同免疫方案制备肠道病毒71型抗血清的免疫效果比较[J]. 山东大学学报(医学版), 2012, 50(3): 129-.
[13] 李志会,岳盈盈,宋楠楠,李鹏,孟红. 制备肠道病毒71型黏膜疫苗的初步探索[J]. 山东大学学报(医学版), 2012, 50(2): 25-.
[14] 岳盈盈1,张颖2,李鹏1,李志会1,宋楠楠1,纪璇1,盖中涛2,孟红1. [J]. 山东大学学报(医学版), 2012, 50(2): 106-109.
[15] 李鹏1,张颖2,岳盈盈1,宋楠楠1,李志会1,盖中涛2,孟红1. 肠道病毒71型山东分离株全基因组序列分析[J]. 山东大学学报(医学版), 2011, 49(10): 113-117.
Viewed
Full text


Abstract

Cited

  Shared   
  Discussed   
[1] 索东阳,申飞,郭皓,刘力畅,杨惠敏,杨向东. Tim-3在药物性急性肾损伤动物模型中的表达及作用机制[J]. 山东大学学报 (医学版), 2020, 1(7): 1 -6 .
[2] 马青源,蒲沛东,韩飞,王超,朱洲均,王维山,史晨辉. miR-27b-3p调控SMAD1对骨肉瘤细胞增殖、迁移和侵袭作用的影响[J]. 山东大学学报 (医学版), 2020, 1(7): 32 -37 .
[3] 李宁,李娟,谢艳,李培龙,王允山,杜鲁涛,王传新. 长链非编码RNA AL109955.1在80例结直肠癌组织中的表达及对细胞增殖与迁移侵袭的影响[J]. 山东大学学报 (医学版), 2020, 1(7): 38 -46 .
[4] 徐玉香,刘煜东,张蓬,段瑞生. 101例脑小血管病患者脑微出血危险因素的回顾性分析[J]. 山东大学学报 (医学版), 2020, 1(7): 67 -71 .
[5] 罗昕,何兵,聂清生,侯震波,董军,李玉花,曾祥芹,刘伟,孔德民,曹金凤. 磁共振扩散加权成像单指数模型与扩散峰度成像模型在61例肾透明细胞癌分级中的对比[J]. 山东大学学报 (医学版), 2020, 1(7): 89 -95 .
[6] 张迪,于猛,刘霞. 神经调控技术简述[J]. 山东大学学报 (医学版), 2020, 1(8): 50 -60 .
[7] 张伟,谭文浩,李贻斌. 基于深度强化学习的四足机器人运动控制发展现状与展望[J]. 山东大学学报 (医学版), 2020, 1(8): 61 -66 .
[8] 陈安静,张训. 靶向小类泛素化修饰的胶质瘤治疗新策略[J]. 山东大学学报 (医学版), 2020, 1(8): 88 -94 .
[9] 张洪彬,赵寒辉,王素霞,周鹏,贺青卿,王延群,丁伟平,柳刚. 303例甲状旁腺切除术围术期观察及术后严重低钙血症危险因素分析[J]. 山东大学学报 (医学版), 2020, 1(9): 14 -20 .
[10] 孙薏丰,高玉,梁永媛,高杨. CPLX2在30例肝癌组织的表达及其对体外细胞增殖与侵袭的影响[J]. 山东大学学报 (医学版), 2020, 1(9): 34 -39 .