柯萨奇病毒B组5型山东分离株基因特征分析  

Genomic characterizations of coxsackievirus B5 strains isolated from Shandong Province,China

作　　者：曹梦圆 崔亚楠 王敏 姚雪 韦庆娟 胡弢 邢薇佳 史卫峰 李娟 CAO Mengyuan;CUI Ya'nan;WANG Min;YAO Xue;WEI Qingjuan;HU Tao;XING Weijia;SHI Weifeng;LI Juan(Key Laboratory of Emerging Infectious Diseases in Universities of Shandong,Shandong First Medical University&Shandong Academy of Medical Sciences,Taian 271000,Shandong,China;Department of Pathogen Biology,School of Clinical and Basic Medical Sciences,Shandong First Medical University&Shandong Academy of Medical Sciences;Taian Center for Disease Control and Prevention;School of Public Health,Shandong First Medical University&Shandong Academy of Medical Sciences;Ji'nan Children's Hospital;Taian Maternal and Child Health Hospital;Ruijin Hospital,Shanghai Jiao Tong University School of Medicine;Shanghai Institute of Virology,Shanghai Jiao Tong University School of Medicine)

机构地区：[1]山东第一医科大学(山东省医学科学院)山东省高等学校新发传染病重点实验室,山东泰安271000 [2]山东第一医科大学(山东省医学科学院)临床与基础医学院(基础医学研究所)病原生物学系 [3]泰安市疾病预防控制中心 [4]山东第一医科大学(山东省医学科学院)公共卫生与健康管理学院 [5]济南市儿童医院 [6]泰安市妇幼保健院 [7]上海交通大学医学院附属瑞金医院 [8]上海交通大学医学院上海市病毒研究院

出　　处：《中国病原生物学杂志》2024年第6期659-664,670,共7页Journal of Pathogen Biology

基　　金：国家自然科学基金(No.81902065);山东省自然科学基金(No.ZR2018PH034);泰山学者工程专项(No.tsqn202211217);山东第一医科大学“学术提升计划”(No.2019QL006)。

摘　　要：目的探明山东11株柯萨奇病毒B组5型(CVB5)的全基因组特征,探讨CVB5病毒遗传进化规律。方法采集2020年山东省手足口病患者的粪便样本,通过临床样本荧光定量检测、病毒分离、高通量和一代测序验证,共获得11株CVB5分离株,同时结合GenBank公共数据库中收录的CVB5病毒株全长基因组和结构蛋白VP1基因序列,构建最大似然系统进化树,研究CVB5基因特征和遗传进化规律。结果11株CVB5分离株全长基因组呈高度核苷酸和氨基酸相似性(>99.9%),与多数2008-2020年我国流行毒株均位于全基因组进化树的Group 4分支,且与2013年江苏省分离株417核苷酸相似性最高,为96.8%;11株CVB5分离株与Group 4参考株相比,P3区3A、3B、3C和3D基因核苷酸同源性均低于P1和P2区其他基因,且多为同义突变;11株CVB5分离株VP1基因位于我国主要流行亚型即C4基因亚型中,与2018年山东省分离株SWG14、SWG44、JN18120亲缘关系较近,核苷酸同源性为96.1%~98.2%。结论CVB5毒株在我国多地持续流行,11株山东分离株同国内多数CVB5株的全基因组及VP1基因均位于同一进化分支,说明11株分离株均为近期国内流行株,它们所在Group 4为国内优势流行分支,C4基因亚型为国内VP1基因流行亚型。Objective To investigate the complete genome characteristics of 11 coxsackievirus B5(CVB5)strains isolated from Shandong Province,and to explore the genetic evolutionary patterns of CVB5.Methods Fecal samples from hand,foot and mouth disease patients in Shandong Province in 2020 were collected.Through RT-qPCR amplification,virus isolation,high-throughput sequencing,and Sanger sequencing,a total of 11 CVB5 isolates were identified.All complete genome sequences and the full-length VP1 gene sequences of CVB5 strains available from GenBank were downloaded as reference sequences.Multiple sequence alignment was performed with MAFFT v7.490.The maximum likelihood(ML)phylogenetic tree was constructedusing RaxML v8.2.12,to analyze the viral genomic characteristics.Results Full-length genomes of the 11 CVB5 strains from the present study showed high nucleotide and amino acid identities(>99.9%).Phylogenetic analysis revealed that they clustered with the majority of Chinese strains within Group 4 circulating between 2008 and 2020.They shared the highest nucleotide similarity of 96.8%with the strain 417 from Jiangsu Province in 2013.Compared to the CVB5 reference strains in Group 4,the nucleotide similarities of the 3A,3B,3C,and 3D genes in the P3 region of the 11 CVB5 strains were lower than those of other genes in the P1 and P2 regions,and there were numerous synonymous mutations in the region P3.The VP1 gene sequences of the 11 CVB5 strains were classified into the predominant branch in China over the past decade namely the subclade C4.They were closely related to the isolates SWG14,SWG44,and JN18120 from Shandong Province in 2018,with nucleotide similarities of 96.1%-98.2%.Conclusion Our results highlight the constant circulation of CVB5 in China.The 11 CVB5 strains from Shandong Province showed high nucleotide similarity to most domestic CVB5 strains,and were placed within the evolutionary branch with the majority of the CVB5 strains circulating in China.This suggests that they belong to the Group 4 of the complete genome

关 键 词：柯萨奇病毒B组5型(CVB5) 手足口病 全基因组 VP1 遗传进化 

分 类 号：R373.23[医药卫生—病原生物学]