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

Recognition of specific cell surface glycans,mediated by the vp8* domain of the spike protein vp4,is the essential first step in rotavirus (rv) infection. due to lack of direct structural information of virus-ligand interactions,the molecular basis of ligand-controlled host ranges of the major human rvs (p[8] and p[4]) in p[ii] genogroup remains unknown. here,through characterization of a minor p[ii] rv (p[19]) that can infect both animals (pigs) and humans,we made an important advance to fill this knowledge gap by solving the crystal structures of the p[19] vp8* in complex with its ligands. our data showed that p[19] rvs use a novel binding site that differs from the known ones of other genotypes/genogroups. this binding site is capable of interacting with two types of glycans,the mucin core and type 1 histo-blood group antigens (hbgas) with a common glcnac as the central binding saccharide. the binding site is apparently shared by other p[ii] rvs and possibly two genotypes (p[10] and p[12]) in p[i] as shown by their highly conserved glcnac-interacting residues. these data provide strong evidence of evolutionary connections among these human and animal rvs,pointing to a common ancestor in p[i] with a possible animal host origin. while the binding properties to glcnac-containing saccharides are maintained,changes in binding to additional residues,such as those in the polymorphic type 1 hbgas may occur in the course of rv evolution,explaining the complex p[ii] genogroup that mainly causes diseases in humans but also in some animals. © 2017 liu et al.