title: Rotavirus VP8*: phylogeny, host range, and interaction with histo-blood group antigens.
abstract: The distal portion of rotavirus (RV) VP4 spike protein (VP8*) is implicated in binding to cellular receptors, thereby facilitating viral attachment and entry. While VP8* of some animal RVs engage sialic acid, human RVs often attach to and enter cells in a sialic acid-independent manner. A recent study demonstrated that the major human RVs (P[4], P[6], and P[8]) recognize human histo-blood group antigens (HBGAs). In this study, we performed a phylogenetic analysis of RVs and showed further variations of RV interaction with HBGAs. On the basis of the VP8* sequences, RVs are grouped into five P genogroups (P[I] to P[V]), of which P[I], P[IV], and P[V] mainly infect animals, P[II] infects humans, and P[III] infects both animals and humans. The sialic acid-dependent RVs (P[1], P[2], P[3], and P[7]) form a subcluster within P[I], while all three major P genotypes of human RVs (P[4], P[6], and P[8]) are clustered in P[II]. We then characterized three human RVs (P[9], P[14], and P[25]) in P[III] and observed a new pattern of binding to the type A antigen which is distinct from that of the P[II] RVs. The binding was demonstrated by hemagglutination and saliva binding assay using recombinant VP8* and native RVs. Homology modeling and mutagenesis study showed that the locations of the carbohydrate binding interfaces are shared with the sialic acid-dependent RVs, although different amino acids are involved. The P[III] VP8* proteins also bind the A antigens of the porcine and bovine mucins, suggesting the A antigen as a possible factor for cross-species transmission of RVs. Our study suggests that HBGAs play an important role in RV infection and evolution.
authors: Division of Infectious Diseases, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA.
authors: Yang
authors: Y
authors: Liu
authors: Pengwei
authors: P
authors: Huang
authors: Ming
authors: M
authors: Tan
authors: Yiliu
authors: Y
authors: Liu
authors: Jacek
authors: J
authors: Biesiada
authors: Jarek
authors: J
authors: Meller
authors: Alejandro A
authors: AA
authors: Castello
authors: Baoming
authors: B
authors: Jiang
authors: Xi
authors: X
authors: Jiang
mesh_terms: D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D000818:Animals; D001665:Binding Sites; D001789:Blood Group Antigens / Q000502:physiology*; D036022:Capsid Proteins / Q000737:chemistry / Q000235:genetics / Q000276:immunology / Q000502:physiology; D002417:Cattle; D058507:Host Specificity / Q000502:physiology; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009077:Mucins / Q000378:metabolism; D016297:Mutagenesis, Site-Directed; D010802:Phylogeny; D054730:Protein Interaction Domains and Motifs; D016601:RNA-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D012401:Rotavirus / Q000145:classification / Q000235:genetics / Q000472:pathogenicity* / Q000502:physiology; D012400:Rotavirus Infections / Q000276:immunology / Q000635:transmission / Q000821:virology; D012794:Sialic Acids / Q000378:metabolism; D013552:Swine; D017361:Viral Nonstructural Proteins / Q000737:chemistry / Q000235:genetics / Q000276:immunology / Q000502:physiology*
chemical_list: D001789:Blood Group Antigens; D036022:Capsid Proteins; D009077:Mucins; D016601:RNA-Binding Proteins; D011994:Recombinant Proteins; D012794:Sialic Acids; C060339:VP4 protein, Rotavirus; D017361:Viral Nonstructural Proteins; C079234:NS35 protein, rotavirus