Glycan specificity of P[19] rotavirus and comparison with those of other related P genotypes
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Accepted version
Published version
Author(s)
Type
Journal Article
Abstract
The P[19] genotype belongs to the P[II] genogroup of group A rotaviruses (RVs). However, unlike the other P[II] RVs that mainly infects humans, P[19] RVs commonly infect animals (porcine), making P[19] unique to study RV diversity and host ranges. Through in vitro binding assays and saturation transfer difference (STD) 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 those of 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. IMPORTANCE: In this study, we found that this 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.
Date Issued
2016-08-24
Date Acceptance
2016-08-24
Citation
Journal of Virology, 2016, 90 (21), pp.9983-9996
ISSN
1098-5514
Publisher
American Society for Microbiology
Start Page
9983
End Page
9996
Journal / Book Title
Journal of Virology
Volume
90
Issue
21
Copyright Statement
Copyright © 2016 Liu et al. This is an open-access article distributed under the
terms of the Creative Commons Attribution 4.0 International license.
terms of the Creative Commons Attribution 4.0 International license.
License URL
Sponsor
Wellcome Trust
Grant Number
108430/Z/15/Z
Subjects
Virology
06 Biological Sciences
07 Agricultural And Veterinary Sciences
11 Medical And Health Sciences
Publication Status
Published