中國疾控中心病毒病所揭示C組輪狀病毒受體結合特徵
導 讀
輪狀病毒（Rotavirus，RV）是引起病毒性急性胃腸炎的重要病原體之一，可分為10個不同的組。研究人C組RV與宿主受體的相互作用，對於揭示C組RV感染機制、流行特徵、病毒進化以及疫苗研發具有重要指導意義。近日，中國疾病預防控制中心病毒病預防控制所段招軍研究員團隊在C組輪狀病毒受體結合特徵方面取得重要研究進展，發現A型組織血型抗原（HBGA）可能是人C組組輪狀病毒與宿主互作的潛在黏附分子並闡明了人C組輪狀病毒VP8*與A型寡糖受體互作的機制。相關研究成果以Human group C rotavirus VP8*s recognize type Ahisto-blood group antigens as ligands為題，發表在國際病毒學專業期刊Journal of Virology 上。
研究背景
輪狀病毒（Rotavirus，RV）是引起病毒性急性胃腸炎的重要病原體之一，可分為10個不同的組。A組RV在人群中廣泛流行，B組、C組和H組RV的流行水平相對較低。C組RV首次在豬身上被發現，隨後在人類中發現。動物C組RV是豬胃腸炎的重要病原體，同時C組RV也可以感染狗、牛和雪貂。人C組RV是人類中第二常見的RVs種類，與A組RV主要感染嬰幼兒不同，C組RV既可以感染兒童。研究人C組RV與宿主受體的相互作用，對於揭示C組RV感染機制、流行特徵、病毒進化以及疫苗研發具有重要指導意義。
結果速覽
1. 本研究針對人C組RV VP8*蛋白，利用糖點陣實驗、寡糖結合實驗、唾液結合實驗、血凝實驗等方法研究其與組織血型抗原（Histo-blood group antigens，HBGAs）之間的關係（圖1）。結果發現：寡糖結合實驗中人C組RV VP8*蛋白特異地與A型HBGA結合。同樣的，在唾液結合實驗中也觀察到人C組RV VP8*蛋白與A、AB型唾液結合，與B、O、O-（非分泌型）唾液不結合，血凝實驗結果也表明VP8*蛋白特異的凝集A和AB型紅細胞。這些結果顯示A型HBGA可能是人C組RV與宿主互作的潛在黏附分子。
圖1. 2016-2017 GII.P16-GII.2諾如病毒VP1基因序列進化樹分析
2.通過晶體學方法解析了人C組RV VP8*，發現人C組RV VP8*具有與A組RV VP8*不同的結構特徵（圖2）。進一步解析VP8*-A三糖的複合物結構發現人C組RV VP8*受體結合位點及受體結合機制也是與A組RV不同的。根據VP8*序列分析，人C組RV VP8*相對保守，同屬於P[2]基因型。
圖2人C組輪狀病毒VP8*蛋白與A三糖的複合物結構及作用機制
結 語
ABSTRACT
Group/species C rotaviruses (RVCs) have been identi?ed as important pathogens of acute gastroenteritis (AGE) in children, family-based outbreaks, as well as animal infections. However, little is known regarding their host-speci?c interaction, infection, and pathogenesis. In this study, we performed serial studies to characterize the function and structural features of a human G4P[2] RVC VP8*that is responsible for the host receptor interaction. Glycan microarrays demonstrated that the human RVC VP8* recognizes type A histo-blood group antigens (HBGAs), which was con?rmed by synthetic glycan-/saliva-based binding assays and hemagglutination of red blood cells, establishing a paradigm of RVCVP8*-glycan interactions. Furthermore, the high-resolution crystal structure of the human RVC VP8* was solved, showing a typical galectin-like structure consisting of two-sheets but with signi?cant differences from cogent proteins of group A rotaviruses (RVAs). The VP8* in complex with a type A trisaccharide displays a novel ligand binding site that consists of a particular set of amino acid residues of the C-D, G-H, and K-L loops. RVC VP8* interacts with type A HBGAs through a unique mechanism compared with that used by RVAs. Our ?ndings shed light on the host-virus interaction and the coevolution of RVCs and will facilitate the development of speci?c antivirals and vaccines.
IMPORTANCE
Group/speciesC rotaviruses (RVCs), members of Reoviridae family, infect both humans and animals, but our knowledge about the host factors that control host susceptibility and speci?city is rudimentary. In this work, we characterized the glycan binding speci?city and structural basis of a human RVC that recognizes type A HBGAs. We found that human RVC VP8*, the rotavirus host ligand binding domain that shares only 15% homology with the VP8* domains of RVAs, recognizes type A HBGA at an as-yet-unknown glycan binding site through a mechanism distinct from that used by RVAs. Our new advancements provide insights into RVC cell attachment, the critical step of virus infection, which will in turn help the development of control and prevention strategies against RVs.
參考文獻：
1. Xiaoman Sun, Lihong Wang, Jianxun Qi, Dandi Li, Mengxuan Wang,Xin Cong, Ruchao Peng, Wengang Chai, Qing Zhang, Hong Wang, Hongling Wen,George F. Gao, Ming Tan and Zhaojun Duan.Human Group C Rotavirus VP8*s Recognize Type A Histo-Blood Group Antigens as Ligands.J. Virol.June 2018 vol. 92 no. 11 e00442-18
doi: 10.1128/JVI.00442-18
本期編輯：Annabella
TAG:病毒學界 |