Lewis结合型诺罗病毒衣壳蛋白与血型寡糖的结构功能研究

Norovirus is the main cause for outbreaks of non-bacterial gastroenteritis around the world. The virus is highly contagious and adaptable, and usually breaks out each year worldwide, causing death to seriously infected patients by depletion of water. Previous studies have shown that different noroviruses can recognize different human histo-blood group antigens(HBGA) as receptors by binding to the outermost oligosaccharides. Up to now, eight receptor binding patterns have been identified representing norovirus' various binding abilities with different types of HBGA. Our application project is based on Boxer strain from G-I genogroup and OIF strain from G-II genogroup, both recognizing Lewis-type HBGA, which is currently not a well understood area concerning the structure and function of virus capsid-Lewis oligosaccharide receptor complexes. Therefore solving the structures of these two capsid proteins in complex with Lewis oligosaccharides followed by functional studies will not only help elucidate the human receptor recognition, invasion and infection of norovirus but will also provide scientific basis for understanding the evolutionary relationship between norovirus and human host cells. It will also be an important guide to designing novel drugs against different noroviruses.

诺罗病毒作为引起人类非细菌型胃肠炎的主要病原体，具有高度传染性和宿主适应性,每年在世界多次爆发，严重感染者可导致脱水并死亡。不同诺罗病毒能识别人类宿主细胞表面不同类型的组织血型抗原（HBGA），其识别主要通过病毒衣壳蛋白与HBGA末端的寡糖残基结合来完成。迄今为止，已总共发现了8种诺罗病毒与HBGA的识别模式。本项目的研究对象是诺罗病毒G-I基因群的Boxer病毒株与G-II基因群的OIF病毒株，主要识别Lewis型血型抗原，且目前对诺罗病毒中Lewis结合型的病毒衣壳蛋白和寡糖受体复合物尚未有深入的结构与功能研究。通过对此两种衣壳蛋白与Lewis型寡糖复合物的结构功能研究，能为诺罗病毒与组织血型抗原的识别作用和病毒侵染过程的研究提供全面、合理的结构解释，对深入了解宿主细胞和诺罗病毒衣壳蛋白在长期进化过程中的相互选择与分化具有重要指导意义，同时也为研发抗诺罗病毒新型药物提供重要的科学依据。

诺罗病毒属于杯状病毒科，是引起人类非细菌性传染性急性胃肠炎最主要的病原体，在全世界范围内都具有较高的发病率和传染性。诺罗病毒能够通过与人类组织-血型抗原结合对宿主进行特异性侵染，其中，GI与GII基因族采用两种截然不同的结合模式。本项目的主要研究对象是诺罗病毒GI基因群的Boxer病毒株与GII基因群的OIF病毒株，主要识别Lewis型血型抗原。通过对此两种衣壳蛋白与Lewis型寡糖复合物的结构功能研究，能为诺罗病毒与组织血型抗原的识别作用和病毒侵染过程的研究提供全面、合理的结构解释,为诺罗病毒的预防和药物治疗提供新的策略和思路，为更深入地研究诺罗病毒与宿主相互作用、宿主范围以及疾病防控、疫苗和抗病毒药物研发等提供坚实的科学依据。