戊型肝炎病毒基因1型和基因4型中和表位区域分子差异研究  

The Molecular Differences between Genotype 1 and Genotype 4 of HEV in Their Neutralization Region

作　　者：郭清顺[1] 葛胜祥[1] 熊君辉[1] 闫强[1] 李少伟[1] 顾颖[1] 徐平东[1] 史维国[1] 张军[1] 夏宁邵[1] 

机构地区：[1]厦门大学国家传染病诊断试剂与疫苗工程技术研究中心厦门大学生命科学学院,福建厦门361005

出　　处：《病毒学报》2007年第6期454-458,共5页Chinese Journal of Virology

基　　金：863计划(2005DFA30820);国家自然科学基金(30500092);国家自然科学基金(30600106);福建省科技重大专项(2004YZ01-1)

摘　　要：戊型肝炎病毒（HEV）根据易感宿主的差别可以分为两大类：一类只分离自人的H（Human）类，包括HEV-1和HEV-2；一类为人畜共患的Z（Zoonosis）类，包括HEV3和HEV-4。本研究通过比较这两类HEV的ORF2aa368-606区段，发现存在4个类保守的差异位点，均位于HEV的主要中和表位区域aa459～606，分别是aa483、aa492、aa497和aa599；对这四个位点进行定点替换突变，以一组能够捕获HEV-1和／或HEV-4的单克隆抗体比较各种突变体的免疫反应性，结果表明仅aa497的差异造成了这两类HEV中和表位构象的部分差异，提示aa497及其相关的病毒表面结构差异在H类和Z类HEV宿主选择中可能扮演重要角色。HEV is classified into H （human） group and Z （zoonosis） group according to its compatible host. H group contains genotype 1 and genotype 2 HEV isolates which infect human only; Z group contains genotype 3 and genotype 4 HEV isolates which infect both human and animals. After analysis of amino acid sequences between ORF2 aa368 and aa606, four group-conserved sites that were all located in the neutralization region of ORF2 were identified. They are aa483, aa492, aa497 and aa599. Mutation analysis and capture PCR were then performed on these sites with a group of monoclonal antibodies. Results showed that the difference of the aa497 between H and Z groups was responsible for the maintenance of their group-specific immunodominant epitopes, probably through confirmation-dependent epitope changes. Thus, aa497 and its related change on the surface structure of HEV may play important roles in host selection by H and Z groups of HEV.

关 键 词：戊型肝炎病毒 宿主差异 中和表位 

分 类 号：R373[医药卫生—病原生物学] Q78[医药卫生—基础医学]