title: Glycan Specificity of P[19] Rotavirus and Comparison with Those of Related P Genotypes.
abstract: The P[19] genotype belongs to the P[II] genogroup of group A rotaviruses (RVs). However, unlike the other P[II] RVs, which mainly infect humans, P[19] RVs commonly infect animals (pigs), making P[19] unique for the study of RV diversity and host ranges. Through in vitro binding assays and saturation transfer difference (STD) nuclear magnetic resonance (NMR), we found that P[19] could bind mucin cores 2, 4, and 6, as well as type 1 histo-blood group antigens (HBGAs). The common sequences of these glycans serve as minimal binding units, while additional residues, such as the A, B, H, and Lewis epitopes of the type 1 HBGAs, can further define the binding outcomes and therefore likely the host ranges for P[19] RVs. This complex binding property of P[19] is shared with the other three P[II] RVs (P[4], P[6], and P[8]) in that all of them recognized the type 1 HBGA precursor, although P[4] and P[8], but not P[6], also bind to mucin cores. Moreover, while essential for P[4] and P[8] binding, the addition of the Lewis epitope blocked P[6] and P[19] binding to type 1 HBGAs. Chemical-shift NMR of P[19] VP8* identified a ligand binding interface that has shifted away from the known RV P-genotype binding sites but is conserved among all P[II] RVs and two P[I] RVs (P[10] and P[12]), suggesting an evolutionary connection among these human and animal RVs. Taken together, these data are important for hypotheses on potential mechanisms for RV diversity, host ranges, and cross-species transmission.
  
  
  OBJECTIVE
  In this study, we found that our P[19] strain and other P[II] RVs recognize mucin cores and the type 1 HBGA precursors as the minimal functional units and that additional saccharides adjacent to these units can alter binding outcomes and thereby possibly host ranges. These data may help to explain why some P[II] RVs, such as P[6] and P[19], commonly infect animals but rarely humans, while others, such as the P[4] and P[8] RVs, mainly infect humans and are predominant over other P genotypes. Elucidation of the molecular bases for strain-specific host ranges and cross-species transmission of these human and animal RVs is important to understand RV epidemiology and disease burden, which may impact development of control and prevention strategies against RV gastroenteritis.
authors: Division of Infectious Diseases, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.
authors: Yang
authors: Y
authors: Liu
authors: Department of Chemistry and Biochemistry, Miami University, Oxford, Ohio, USA.
authors: Theresa A
authors: TA
authors: Ramelot
authors: Division of Infectious Diseases, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.
authors: Pengwei
authors: P
authors: Huang
authors: Glycosciences Laboratory, Department of Medicine, Imperial College London, London, United Kingdom.
authors: Yan
authors: Y
authors: Liu
authors: Glycosciences Laboratory, Department of Medicine, Imperial College London, London, United Kingdom.
authors: Zhen
authors: Z
authors: Li
authors: Glycosciences Laboratory, Department of Medicine, Imperial College London, London, United Kingdom.
authors: Ten
authors: T
authors: Feizi
authors: Division of Infectious Diseases, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.
authors: Weiming
authors: W
authors: Zhong
authors: Center for Research, Diagnostics and Vaccine Development, Centers for Disease Control, Taipei, Taiwan.
authors: Fang-Tzy
authors: FT
authors: Wu
authors: Division of Infectious Diseases, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA.
authors: Ming
authors: M
authors: Tan
authors: Department of Chemistry and Biochemistry, Miami University, Oxford, Ohio, USA.
authors: Michael A
authors: MA
authors: Kennedy
authors: Division of Infectious Diseases, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA Jason.jiang@cchmc.org.
authors: Xi
authors: X
authors: Jiang
mesh_terms: D000818:Animals; D001665:Binding Sites / Q000235:genetics; D001789:Blood Group Antigens / Q000235:genetics; D000939:Epitopes / Q000235:genetics; D005759:Gastroenteritis / Q000821:virology; D005838:Genotype; D058507:Host Specificity / Q000235:genetics; D006801:Humans; D009077:Mucins / Q000235:genetics; D011134:Polysaccharides / Q000235:genetics*; D011485:Protein Binding / Q000235:genetics; D012401:Rotavirus / Q000235:genetics*; D012400:Rotavirus Infections / Q000821:virology*; D013552:Swine; D017361:Viral Nonstructural Proteins / Q000235:genetics; D053585:Virus Attachment
chemical_list: D001789:Blood Group Antigens; D000939:Epitopes; D009077:Mucins; D011134:Polysaccharides; D017361:Viral Nonstructural Proteins