柯萨奇病毒A组6型构象表位的生物信息学预测  

Bioinformatics-Based Prediction of Conformational Epitopes for Coxsackievirus A6

作　　者：王丽萍 戎浩 方雨露 陈琴 董长征 WANG Liping;RONG Hao;FANG Yulu;CHEN Qin;DONG Changzheng(Department of Preventive Medicine,School of Medicine,Ningbo University,Ningbo 315211,China;Zhejiang Provincial Key Laboratory of Pathological and Physiological Technology,Ningbo 315211,China;Hwa Mei Hospital,University of Chinese Academy of Sciences(Ningbo No.2 Hospital),Ningbo 315010,China)

机构地区：[1]宁波大学医学院预防医学系,宁波315211 [2]浙江省病理生理学技术研究重点实验室,宁波315211 [3]中国科学院大学宁波华美医院(宁波市第二医院),宁波315010

出　　处：《病毒学报》2020年第6期1075-1084,共10页Chinese Journal of Virology

基　　金：浙江省基础公益研究计划项目(项目号:LGF18C060001),题目:人肠道病毒构象表位研究及在手足口病疫情监测预警中的应用;宁波市自然科学基金(项目号:2018A610240),题目:人肠道病毒构象表位的生物信息学研究;宁波大学研究生科研创新基金(项目号:G19131),题目:人肠道病毒A组构象表位的生物信息学研究;宁波大学“大学生科研创新计划”(项目号:2019SRIP1921),题目:柯萨奇病毒A组10型的生物信息学研究。

摘　　要：柯萨奇病毒A组6型(Coxsackievirus A6,CV-A6)近年成为手足口病(Hand,foot,and mouth disease,HFMD)最重要的病原体之一。本实验室在之前的研究中发展了人肠道病毒构象表位的生物信息学预测算法,并成功应用于柯萨奇病毒A组10型(Coxsackievirus A10,CV-A10)构象表位的预测,发现CV-A10的构象表位在病毒衣壳表面呈现site 1、site 2和site 3三簇分布。本研究中,应用相同算法对CV-A6的构象表位进行系统性预测,并将CV-A6和CV-A10这两种手足口病的病原体的构象表位进行对比。结果显示:CV-A6(A颗粒)和CV-A10(A颗粒)的构象表位具有高度一致的site 1、site 2和site 3三簇分布模式,而且这种分布一致性超过了CV-A10两种颗粒状态(A颗粒和成熟颗粒)的一致性,说明衣壳结构和颗粒状态对于构象表位非常重要。虽然CV-A6(A颗粒)和CV-A10(A颗粒)具有高度一致的构象表位分布模式,但在共享的58个氨基酸残基位点中,仅有21个(36.2%)残基保守,而且绝大多数构象表位都有3个以上残基差异,提示构象表位残基上的差异造成了CV-A6和CV-A10的血清型差异。CV-A6构象表位的预测结果,为其构象表位的实验鉴定、分子流行病学研究和疫苗研发提供了重要支持。Coxsackievirus A6(CV-A6)has emerged as one of the predominant pathogens of hand,foot,and mouth disease(HFMD).A bioinformatics-based algorithm of conformational epitopes for human enteroviruses has been developed by our research team previously and applied to predict the conformational epitopes of CV-A10.These epitopes on the surface of viral capsids were clustered into three sites:site 1,site 2 and site 3.In the present study,we used the same algorithm to systematically predict the conformational epitopes of CV-A6 and compared the predicted epitopes of CV-A6 and CV-A10(both of which cause HFMD).Results revealed that the conformational epitopes of CV-A6(A-particle)and CV-A10(A-particle)are highly consistent in three sites(site 1,2 and 3)distribution pattern.This distribution consistency exceeded that between two particles(Aparticle and mature particle)of CV-A10,which suggested that the capsid structure and particle state were crucial for conformational epitopes.Even though the conformational epitopes of CV-A6(A-particle)and CVA10(A-particle)showed similar distribution patterns,only 21(36.2%)of 58 sites of amino-acid residues shared by these two viruses were conserved,and more than three residues varied in most epitopes.These data suggested that residue diversity in conformational epitopes contributed to the serotype difference of CV-A6 and CV-A10.Our prediction results of CV-A6 are important for providing support for experimental identification of conformational epitopes,molecular epidemiological studies and vaccine design.

关 键 词：柯萨奇病毒A组6型(CV-A6) 柯萨奇病毒A组10型(CV-A10) 构象表位 抗原表位 生物信息学预测 手足口病(HFMD) 

分 类 号：R373.2[医药卫生—病原生物学] R511[医药卫生—基础医学]