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Publication Abstract from PubMed

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[lsqb]2[rsqb] RVC VP8* that is responsible for host receptor interaction. Glycan microarrays demonstrated that the human RVC VP8* recognizes type A histo-blood 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, high resolution crystal structure of the human RVC VP8* was solved, showing a typical galectin-like structure consisting of two beta-sheets but with significant differences to cogent proteins of 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 (aa) residues of the C-D, G-H, and K-L loops. RVC VP8* interacts with type A HBGAs through a unique mechanism compared with RVAs. Our findings shed light on the host-virus interaction and co-evolution of RVCs and will facilitate the development of specific antivirals and vaccines.IMPORTANCE Group/species C rotaviruses (RVCs), members of Reoviridae 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 RV host ligand binding domain that shares only approximately 15% homology to those of RVAs, recognizes type A HBGA at an as-yet-unknown glycan binding site through a distinct mechanism compared with 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.

Human group C rotavirus VP8*s recognize type A histo-blood group antigens as ligands.,Sun X, Wang L, Qi J, Li D, Wang M, Cong X, Peng R, Chai W, Zhang Q, Wang H, Wen H, Gao GF, Tan M, Duan Z J Virol. 2018 Mar 28. pii: JVI.00442-18. doi: 10.1128/JVI.00442-18. PMID:29593033^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.