摘要
埃可病毒18型(Echovirus 18,E18)可引起手足口病、病毒性脑膜炎和急性胃肠炎等疾病,近20年来开始在全球流行.本文首先使用前期研发的人肠道病毒构象表位的生物信息学预测算法,对肠道病毒B种的E18构象表位进行系统性预测,发现其表位分布模式呈三簇分布,其中VP1 BC环和C-端、VP2 EF环是E18表位的主要构成区域;其次基于E18的VP1和基因组序列的分子进化分析发现,进化分支的形成伴随表位处氨基酸突变,而VP1 C-端和VP2 EF环是突变热点区域;最后通过足迹图发现,大多数E18衣壳表面的分支突变都位于表位上或附近,受体结合位置处的突变罕见,提示表位处的突变产生了新的进化分支,但分支突变尽量避开受体结合位置,以免影响病毒与宿主细胞的结合能力.E18构象表位的生物信息学研究,为进一步通过实验鉴定表位、病毒的监测和预警以及抗病毒药物和疫苗的研发提供了重要支持.
Echovirus 18(E18)causes aseptic meningitis(AM),hand-foot-mouth disease(HFMD),and acute gastroenteritis,which has been prevalent worldwide for the last two decades.In the present study,a bioinformatics-based algorithm of conformational epitopes for human enteroviruses developed previously was used to systematically predict the conformational epitopes of E18 of enterovirus B.The results show that the epitopes were distributed into three clusters,where the VP1 BC loop,VP1 C-terminus and VP2 EF loop were the main regions of E18 epitopes.Further,molecular evolution analysis based on the VP1 and genome sequences of E18 revealed that the emergence of evolutionary clades was accompanied by amino acid mutations on epitopes,and the VP1 C-terminus and VP2 EF loop were mutation hotspot regions.Finally,the roadmap revealed that most of the clade-specific mutations on the E18 capsid surface were located on or near the epitopes,while mutations on the receptor binding sites were rare.This suggested that the mutations on the epitopes give rise to a new evolutionary clade,but the clade-specific mutations try to avoid the receptor binding site so as not to affect the ability of the virus to bind to the host cells.The bioinformatics study of E18 conformational epitopes provides important support for experimental identification of epitopes,virus surveillance and early warning,and the development of antiviral drugs and vaccines.
作者
王惠
贾永涛
方雨露
董长征
WANG Hui;JIA Yongtao;FANG Yulu;DONG Changzheng(School of Medicine,Ningbo University,Ningbo 315211,China;Zhejiang Provincial Key Laboratory of Pathological and Physiological Technology,Ningbo 315211,China)
出处
《宁波大学学报（理工版）》
CAS
2023年第1期75-83,共9页
Journal of Ningbo University：Natural Science and Engineering Edition
基金
浙江省基础公益研究计划项目(LGF18C060001)
宁波市公益项目(2021S135)
宁波大学研究生科研创新基金(IF2022190)。
关键词
埃可病毒18型
肠道病毒
构象表位
抗原表位
分子进化分析
生物信息学
echovirus 18
enterovirus
conformational epitope
antigenic epitope
molecular evolutionary analysis
bioinformatics
