Key Laboratory of Medical Virology and Viral Diseases, Ministry of Health of the People's Republic of China, Beijing, China.
National Institute for Viral Disease Control and Prevention, China CDC, Beijing, China.
J Virol. 2018 May 14;92(11). doi: 10.1128/JVI.00442-18. Print 2018 Jun 1.
Group/species C rotaviruses (RVCs) have been identified as important pathogens of acute gastroenteritis (AGE) in children, family-based outbreaks, as well as animal infections. However, little is known regarding their host-specific 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 confirmed by synthetic glycan-/saliva-based binding assays and hemagglutination of red blood cells, establishing a paradigm of RVC VP8*-glycan interactions. Furthermore, the high-resolution crystal structure of the human RVC VP8* was solved, showing a typical galectin-like structure consisting of two β-sheets but with significant 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 findings shed light on the host-virus interaction and the coevolution of RVCs and will facilitate the development of specific antivirals and vaccines. Group/species C rotaviruses (RVCs), members of family, infect both humans and animals, but our knowledge about the host factors that control host susceptibility and specificity is rudimentary. In this work, we characterized the glycan binding specificity 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.
组/种 C 轮状病毒（RVC）已被确定为儿童急性胃肠炎（AGE）、家族性暴发以及动物感染的重要病原体。然而，对于其宿主特异性相互作用、感染和发病机制知之甚少。在这项研究中，我们进行了一系列研究，以表征负责宿主受体相互作用的人 G4P[2]RVCVP8的功能和结构特征。糖组芯片表明，人 RVCVP8识别 A 型组织血型抗原（HBGA），这通过合成聚糖/唾液结合测定和红细胞的血凝作用得到证实，确立了 RVCVP8*-聚糖相互作用的范例。此外，还解析了人 RVCVP8的高分辨率晶体结构，显示出一种典型的半乳凝集素样结构，由两个β-片层组成，但与 A 型轮状病毒（RVAs）的相关蛋白有显著差异。VP8与 A 型三糖复合物显示出一个新的配体结合位点，该位点由 C-D、G-H 和 K-L 环的一组特定氨基酸残基组成。与 RVAs 相比，RVCVP8*通过独特的机制与 A 型 HBGA 相互作用。我们的发现揭示了宿主-病毒相互作用以及 RVC 的共同进化，将有助于开发特定的抗病毒药物和疫苗。
组/种 C 轮状病毒（RVC）属于家族，感染人和动物，但我们对控制宿主易感性和特异性的宿主因素的了解还很基础。在这项工作中，我们对识别 A 型 HBGA 的人 RVC 的聚糖结合特异性和结构基础进行了表征。我们发现，人 RVCVP8*，与 RVAVP8*结构域仅共享约 15%同源性的轮状病毒宿主配体结合结构域，通过一种与 RVAs 不同的机制识别 A 型 HBGA。我们的新进展提供了关于 RVC-细胞附着的见解，这是病毒感染的关键步骤，这反过来将有助于开发针对 RV 的控制和预防策略。
