人轮状病毒感染与组织血型抗原相关性研究

项目名称： 人轮状病毒感染与组织血型抗原相关性研究

项目编号： No.81472003

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 段招军

作者单位： 中国疾病预防控制中心病毒病预防控制所

项目金额： 72万元

中文摘要： 轮状病毒（RV）是引起全球儿童重症腹泻的重要病原，其疾病负担巨大。最新研究发现组织血型抗原（HBGAs）可能是人RV的识别受体，但仅有少数基因型人RV的HBGAs结合模式被确定。不同基因型人RV的HBGAs结合模式、相互作用的分子基础及HBGAs在RV感染中的作用尚不清楚。本项目拟表达不同基因型人RV VP8*蛋白和培养不同基因型RV中国流行株进行HBGAs结合分析（唾液和寡糖）；再利用分子对接模拟导出不同基因型RV与HBGAs结合面氨基酸残基，应用定点突变技术确定不同基因型RV与HBGAs结合的分子基础；构建特异HBGAs、整合素以及热休克蛋白70基因工程细胞株，通过与RV粒子的结合、封闭阻断实验来确定HBGAs在RV感染中的作用；最后通过分子流行病学确定人RV主要流行株（基因型）与HBGAs在临床感染中的相互关系。本课题将为RV新型疫苗设计、感染发病及跨种传播和进化机制的阐明奠定基础。

中文关键词： 轮状病毒；组织血型抗原；重症腹泻；受体；基因型

英文摘要： Rotavirus (RV) is the important pathogen causing the severe diarrhea in children with < 5 years of age. The disease burden caused by RV is large. The previous studies indicated that sialic acids (SA) are the receptor for some animal RVs. However, all human RVs were SA independent (sialidase-insensitive). The recent several studies found that RVs recognize the histo-blood group antigens (HBGAs) as potential receptor. However, so far the HBGA patterns have been only identified in several human RV genotypes. It was still unknown that the HBGA patterns for all different human RV genotypes, the molecular basis for the correlation of the RV with HBGAs and the role of HBGAs in RV infection. In this study, the binding assay (based on saliva and synthesized oligosaccharides) of VP8* protein and cell cultured RV particle of different RV genotypes will be conducted. Amino acids from the binding surface between RVs and HBGAs will be deduced. The molecular basis between RVs and HBGAs will be identified by the site-mutagenesis. The engineered cell lines for special HBGAs, integrin and heat shock protein 70 will be established. The role of HBGAs in RV infection will be identified by the binding assay and inhibiting and blocking assay. Finally, the correlation of HBGAs with RV predominant strains in clinical infection will be identified. This grant will give the basis on the design for novel RV vaccines, the mechanism of infection, cross-species transmission and evolution of the RV.

英文关键词： Rotavirus;histo-blood group antigen;Severe Diarrhea;receptor;genotype