2013-2019年全国手足口病ECHO-9的分子流行病学研究

埃可病毒9型(Echovirus 9,ECHO-9)是引起无菌性脑膜炎(Aseptic meningitis,AM)和手足口病(Hand,foot,and mouth disease,HFMD)暴发流行的重要病原体,但目前全球关于ECHO-9分子流行病学研究仍比较匮乏,ECHO-9基于VP1全长的基因分型结果尚未明确。本研究依托国家HFMD监测网络,2013-2019年在中国大陆共分离到15株ECHO-9毒株,对其进行VP1区全长序列测定和分析,并与GenBank中下载的全部112条ECHO-9VP1区全长序列共同构建系统发育进化树。结果显示,全球ECHO-9分为A-G七个基因型,其中C、D和F基因型可被进一步划分为C1-C2,D1-D4和F1-F2基因亚型。各洲之间优势基因型别有显著差异,亚洲和欧洲分别以D和C基因型为绝对优势基因型。中国大陆ECHO-9优势基因型别为D基因型,但其优势基因亚型随时间推移有明显转变。2000-2005年,中国大陆ECHO-9全部为D1基因亚型,2006年开始出现D1、D2和D3基因亚型的共同流行,2010年后D1和D2基因亚型消失,D3成为中国大陆绝对优势基因型别。本研究测定的15株ECHO-9分离自2013-2019年,其中14株属于D3基因亚型,1株江西ECHO-9为C2基因亚型,推测其可能来源于境外。本研究建立了全球ECHO-9基于VP1全长的基因分型方法,揭示了ECHO-9在全国及全球范围的分子流行特征。

Molecular Epidemiological Study of ECHO-9 Associated with Hand,Foot,and Mouth Disease in China,2013-2019

Echovirus 9(ECHO-9)is an important pathogen which can cause outbreaks of aseptic meningitis(AM)and hand,foot,and mouth disease(HFMD).However,the molecular epidemiology of ECHO-9 is incompletely understood.Also,the genotyping results of ECHO-9 based on the full-length of VP1 are not clear.Based on the National HFMD pathogen surveillance system in China,a total of fifteen ECHO-9 isolates were achieved during 2013-2019,all isolates were subjected to sequencing of the VP1 region and sequences analysis.All ECHO-9 full-length VP1 gene sequences were downloaded from GenBank.Construction of phylogenetic tree was based on the complete VP1 nucleotide sequence of 127 ECHO-9 strains.Results showed that ECHO-9 could be categorized into seven genotypes:A–G.Genotypes C,D,F could be further subdivided into C1–C2,D1–D4 and F1–F2.There were significant differences in the dominant genotypes among different continents.Genotypes D and C were the dominant genes in Asia and Europe,respectively.The dominant genotype of ECHO-9 in the China′s mainland was genotype D,but the dominant gene subtype changed over time.During 2000–2005,all ECHO-9 strains in the China′s mainland were sub-genotype D1.After 2006,sub-genotypes D1,D2 and D3 were common.After 2010,sub-genotypes D1 and D2 disappeared,and D3 became the dominant genotype in the China′s mainland.The fifteen strains of ECHO-9 detected in our study were isolated from 2013 to 2019.Fourteen of them belonged to genotype D3,and one Jiangxi ECHO-9 isolate belonged to genotype C2 which was speculated to be an imported case.In this study,we established the genotyping results of global ECHO-9 based on the full length of VP1,and revealed the molecular epidemiological characteristics of ECHO-9 in China and worldwide.