国内C4基因型EV-A71结构蛋白VP1区第98和145位点分子进化特征的分析  

Analysis of molecular evolutionary characteristics at sites 98 and 145 of structural protein VP1 of domestic C4 genotype EV-A71

作　　者：王浩 韦欢欢 陈飞 黄京京 朱俊萍[1] WANG Hao;WEI Huanhuan;CHEN Fei;HUANG Jingjing;ZHU Junping(Department of Pathogency Biology,School of Basic Medical Sciences,Capital Medical University,Beijing 100069,China)

机构地区：[1]首都医科大学基础医学院病原生物学系,北京100069

出　　处：《微生物学免疫学进展》2023年第5期1-10,共10页Progress In Microbiology and Immunology

摘　　要：目的 分析国内C4基因型肠道病毒A71型(enterovirus A71,EV-A71)结构蛋白VP1区第98和145位点的分子进化特征。方法 构建国内C4型EV-A71 VP1序列数据库,采用选择压力位点分析、易突变位点熵值分析、氨基酸多样性分析3种方法分析国内C4基因型EV-A71不同进化分支的结构蛋白VP1区第98和145位点分子进化的特征,并结合手足口病(hand,foot and mouth disease,HFMD)暴发前后及临床轻重症信息进行分析。结果 国内C4基因型EV-A71流行进化过程,发生了从C4b到C4a-1,再到C4a-2三个进化分支的优势替换,且不同进化分支VP1的选择压力位点不同。VP1区第98和145位点是国内C4型EV-A71进化过程中发生改变的关键氨基酸位点,与病毒毒力和传播特征紧密相关。VP1区第98和145位点氨基酸组合类型主要包括98E145E(EE)占89.24%、98K145E(KE)占6.78%、98E145G(EG)占1.76%、98E145Q(EQ)占1.66%。其中,EE为最常见类型,而KE型与临床重症发生显著相关(P<0.001)。结论 国内EV-A71优势流行毒株仍为C4a-2基因型,结构蛋白VP1区第98和145位点可能是重要的病毒毒力相关位点。Objective To characterize the molecular evolution of C4 EV-A71 VP1-98 and 145 sites in the mainland of China.Methods A domestic VP1 sequence database of C4 EV-A71 was constructed.The structural protein VP1 98 and 145 sites were analyzed by selective pressure,mutation prone site entropy and amino acid diversity,combined with the stages of hand,foot and mouth disease outbreak and clinical symptoms.Results During the epidemic and evolution of C4 EV-A71 in the mainland of China,dominant substitution occurred from C4b to C4a-1 and then to C4a-2,and the selection pressure sites of VP1 in different evolutionary clades were differed.The VP1-98 and 145 sites are the essential amino acid sites changed during the evolution of domestic C4 EV-A71,which might be closely related to virulence and transmission characteristics.Amino acid combinations at VP1-98 and 145 were mainly composed of 98E145E(EE),which accounts for 89.24%,98K145E(KE) representing for 6.78%,98E145G(EG) accounting for 1.76%,and 98E145Q(EQ) make up 1.66%,respectively.Among them,EE was the most common type,while KE was significantly associated with the occurrence of clinically severe disease(P<0.001).Conclusion The dominant circulating strain of EV-A71 in the mainland of China was still the C4a-2 genotype,and the 98 and 145 sites in VP1 region of structural protein might be important virulence related sites.

关 键 词：手足口病 肠道病毒A71型 结构蛋白VP1区第98和145位点 分子进化 病毒毒力相关位点 氨基酸多样性 

分 类 号：R37[医药卫生—病原生物学]