Structural basis of glycan specificity of P[19] VP8*: Implications for rotavirus zoonosis and evolution

• DOI: 10.1371/journal.ppat.1006707
• Publication Date: 2017-11-14T13:46:14Z
• Authors: Yang Liu; Shenyuan Xu; Andrew L. Woodruff; Ming Xia; Ming Tan; Michael A. Kennedy; Xi Jiang
• Keywords: Rotavirus; 0301 basic medicine; Binding Sites; Genotype; QH301-705.5; Genetic Variation; RNA-Binding Proteins; RC581-607; Viral Nonstructural Proteins; Host Specificity; Rotavirus Infections; 3. Good health; 03 medical and health sciences; Polysaccharides; Zoonoses; Animals; Humans; Immunologic diseases. Allergy; Biology (General); Research Article

Recognition of specific cell surface glycans, mediated by the VP8* domain spike protein VP4, is essential first step in rotavirus (RV) infection. Due to lack direct structural information virus-ligand interactions, molecular basis ligand-controlled host ranges major human RVs (P[8] and P[4]) P[II] genogroup remains unknown. Here, through characterization a minor RV (P[19]) that can infect both animals (pigs) humans, we made an important advance fill this knowledge gap solving crystal structures P[19] complex with its ligands. Our data showed use novel binding site differs from known ones other genotypes/genogroups. This capable interacting two types mucin core type 1 histo-blood group antigens (HBGAs) common GlcNAc as central saccharide. The apparently shared possibly genotypes (P[10] P[12]) P[I] shown their highly conserved GlcNAc-interacting residues. These provide strong evidence evolutionary connections among these animal RVs, pointing ancestor possible origin. While properties GlcNAc-containing saccharides are maintained, changes additional residues, such those polymorphic HBGAs may occur course evolution, explaining mainly causes diseases humans but also some animals.