GⅡ.23基因型诺如病毒P蛋白的寡糖结合特征

Glycan Binding Patterns of P Protein of GⅡ.23 Nororirus

诺如病毒(Noroviruses,NoVs)是导致人急性胃肠炎的最重要病原体之一,也是引起食源性疾病暴发的首要病原体。组织血型抗原(Histo-blood groups antigens,HBGAs)是NoVs的受体或宿主易感因子。已有研究表明HBGAs与NoVs的感染和流行高度相关。GⅡ.23是最近报道的NoVs新基因型。为了研究GⅡ.23与HBGAs的结合特征,表达纯化GⅡ.23基因型的P蛋白之后,通过唾液和寡糖结合实验研究其与HBGAs的结合特性,并通过同源结构模拟探索GⅡ.23 P蛋白与糖抗原潜在的对接分子机制,与已经解析的GⅡ.10的P蛋白与岩藻糖的复合物结构进行重叠。结果发现,GⅡ.23 P蛋白可以与B型唾液结合,但不结合A、O^+和O^-非分泌型唾液;P蛋白与H双糖抗原发生结合;分子模拟显示GⅡ.23 P蛋白具有与岩藻糖环结合的类似特征。本研究首次揭示了GⅡ.23 P蛋白与HBGAs受体的结合特征,为深入探索GⅡ.23基因型NoVs的进化、感染以及流行的具体机制提供了基础资料。

Noroviruses(NoVs)cause acute gastroenteritis and the primary pathogens inducing outbreaks of food-borne diseases.Histo-blood groups antigens(HBGAs)might be receptors or host susceptibility factors of NoVs.HBGAs have been shown to be closely associated with NoVs infection and prevalence.The GⅡ.23 genotype of NoVs was reported recently.To study the binding pattern between GⅡ.23 and HBGAs,the P protein of GⅡ.23 were expressed and purified,and the binding feature of P protein to HBGAs was investigated using saliva and glycan binding assays.Homology modeling of P protein was built.The superimposition structural analysis of P protein of GⅡ.10 in complex with fucose was undertaken to explore the possible docking structural basis of P protein of GⅡ.23 and fucose.The results showed that P protein of GⅡ.23 was bound to type B saliva,and not bound to A or O secretors or non-secretor saliva.P protein could bind to the antigens of H disaccharides antigens.Homology modeling indicated that P protein could bind to the antigens of H disaccharides using a potential glycan-binding site.The results suggested an interaction between P protein of GⅡ.23 with HBGAs.These findings offer a potential basis for elucidating the mechanism of the evolution,infection and epidemiology of the GⅡgenotype.