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

PLoS Pathogens

Ming Xia¹  Andrew L. Woodruff¹  Michael A. Kennedy²  Shenyuan Xu²  Ming Tan²  Yang Liu³  Xi Jiang⁴ 

[1] Department of Chemistry and Biochemistry, Miami University, Oxford, OH, United States of America;Division of Infectious Diseases, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, United States of America;Tianjin Key Laboratory of Molecular Nuclear Medicine, Institute of Radiation Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China;University of Cincinnati College of Medicine, Cincinnati, OH, United States of America

关键词: Mucin;    Animal evolution;    Crystal structure;    Evolutionary genetics;    Hydrogen bonding;    Viral evolution;    Host-pathogen interactions;    Rotavirus infection;   

DOI  :  10.1371/journal.ppat.1006707

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

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.

【 授权许可】

CC BY