摘要
目的分析相关疫苗上市后中国大陆肠道病毒71型(enterovirus type 71,EV71)C4亚型的分子流行特征。方法基于贝叶斯的马尔可夫链蒙特卡罗(markov chain monte carlo,MCMC)分析方法,对EV71疫苗上市前后中国大陆EV71毒株VP1基因相似性进行比较。应用贝叶斯天际线模型和SpreaD3 v0.9.6软件对中国大陆C4亚型病毒进行系统发生地理学分析,通过绘制贝叶斯天际线图描绘种群动态历史变化,并应用EasyCodeML软件分析正选择压力位点。结果中国大陆EV71 C4亚型VP1基因序列的平均进化速率为2.25×10-3 site/year,C4a亚型毒株平均进化速率为3.1×10-3 site/year;EV71 C4亚型的起源可追溯至1990年的华东地区,C4a亚型可能起源于1999年。2002—2007年C4亚型经历了种群规模扩张,种群规模于2007年达峰值,且在EV71疫苗上市后仍保持较高水平。C4亚型病毒VP1基因中有5个氨基酸位点承受正选择压力,比对分析EV71疫苗上市后2015—2018年C4亚型病毒序列,筛选到VP1基因第289位点承受正选择压力。结论本研究揭示了EV71 C4亚型的遗传进化信息,为制定手足口病(hand,foot and mouth disease,HFMD)的防控策略提供了科学的数据支持。
Objective To analyze the molecular epidemic characteristics of subtype C4 of enterovirus type71(EV71)in Chinese Mainland after the relevant vaccines were put onto the market.Methods Based on Bayesian markov chain monte carlo(MCMC)analysis,the similarity of VP1 of domestic EV71 strains was evaluated before and after EV71 vaccine was marketed.The virus subtype C4 in Chinese Mainland was analyzed for phylogenetic geography by using Bayesian skyline model and SpreaD3v0.9.6 software,described for historical changes of population dynamics by drawing Bayesian skyline map,and analyzed for positive selection pressure sites by using EasyCodeML software.Results The average evolution rate of VP1 gene of domestic EV71 subtype C4 was 2.25×10-3sites/year,while that of C4a strain was 3.1×10-3 sites/year.The origin ofEV71C4 subtype wastraced back to East China in 1990,and subtype C4a may beoriginated in 1999.From 2002 to 2007,subtype C4 experienced population expansion,of which the population size reached the maximum in 2007,and then remained high even after EV71 vaccine was marketed.The VP1 gene of virus subtype C4 showed five amino acid sites under pressure of positive selection,and site 289 of VP1 under the pressure was screened through comparison of the sequence of virus subtype C4 from 2015 to 2018 after EV71 vaccine was marketed.Conclusion This study revealed the genetic evolution information of EV71 subtype C4,which provided a scientific data support for formulation of prevention and control strategies of HFMD.
作者
杜瑞晓
王茜
刘明琛
高帆
白玉
吴星
毛群颖
梁争论
卞莲莲
DU Rui-xiao;WANG Qian;LIU Ming-chen;GAO Fan;BAI Yu;WU Xing;MAO Qun-ying;LIANG Zheng-lun;BIAN Lian-lian(National Institutes for Food and Drug Control,NHC Key Laboratory of Research on Quality and Standardization of Biotech Products,Beijing 102629,China)
出处
《中国生物制品学杂志》
CAS
CSCD
北大核心
2022年第11期1366-1371,共6页
Chinese Journal of Biologicals
基金
国家科技重大专项(2018ZX09737-011).
关键词
手足口病
肠道病毒71型
C4亚型
进化特征
正选择压力
中国大陆
Hand,foot and mouth disease(HFMD)
Enterovirus type 71(EV71)
Subtype C4
Evolutionary characteristics
Pressure of positive selection
Chinese Mainland
