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A Unique Human Norovirus Lineage with a Distinct HBGA Binding Interface.

Liu W, Chen Y, Jiang X, Xia M, Yang Y, Tan M, Li X, Rao Z - PLoS Pathog. (2015)

Bottom Line: Each of the two major genogroups (GI and GII) of human NoVs recognizes a unique set of HBGAs through a distinct binding interface that is conserved within a genogroup, indicating a distinct evolutionary path for each genogroup.In addition, we found that glycerol inhibits OIF binding to HBGAs, potentially allowing production of cheap antivirals against human NoVs.Taken together, our results reveal a new evolutionary lineage of NoVs selected by HBGAs, a finding that is important for understanding the diversity and widespread nature of NoVs.

View Article: PubMed Central - PubMed

Affiliation: School of Life Sciences, University of Science and Technology of China, Hefei, Anhui, China.

ABSTRACT
Norovirus (NoV) causes epidemic acute gastroenteritis in humans, whereby histo-blood group antigens (HBGAs) play an important role in host susceptibility. Each of the two major genogroups (GI and GII) of human NoVs recognizes a unique set of HBGAs through a distinct binding interface that is conserved within a genogroup, indicating a distinct evolutionary path for each genogroup. Here, we characterize a Lewis a (Lea) antigen binding strain (OIF virus) in the GII.21 genotype that does not share the conserved GII binding interface, revealing a new evolution lineage with a distinct HBGA binding interface. Sequence alignment showed that the major residues contributing to the new HBGA binding interface are conserved among most members of the GII.21, as well as a closely related GII.13 genotype. In addition, we found that glycerol inhibits OIF binding to HBGAs, potentially allowing production of cheap antivirals against human NoVs. Taken together, our results reveal a new evolutionary lineage of NoVs selected by HBGAs, a finding that is important for understanding the diversity and widespread nature of NoVs.

No MeSH data available.


Related in: MedlinePlus

HBGA-binding of wild type and various mutant P particles with single amino acid mutations at the HBGA-binding interface of OIF virus.(A), Binding of wild type OIF P particles with a panel of oligosaccharides representing different HBGAs (A, B, Lea, Leb, Lex, Ley, H1, H2, H3, sialyl Lea and sialyl Lex) and the type 1 (Pre1) and type 2 (Pre 2) precursors. (B to L), Binding of various mutant P particles with single amino acid mutations at the HBGA-binding interface with the same panel of oligosaccharides as in (A). The concentrations of the P particles were 10 μg/ml, while oligosaccharides for plate coating at 2 μg/ml. Y axes indicate the binding signals in optical densities at 450 nm (OD450), while the X-axes indicate different oligosaccharides.
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ppat.1005025.g006: HBGA-binding of wild type and various mutant P particles with single amino acid mutations at the HBGA-binding interface of OIF virus.(A), Binding of wild type OIF P particles with a panel of oligosaccharides representing different HBGAs (A, B, Lea, Leb, Lex, Ley, H1, H2, H3, sialyl Lea and sialyl Lex) and the type 1 (Pre1) and type 2 (Pre 2) precursors. (B to L), Binding of various mutant P particles with single amino acid mutations at the HBGA-binding interface with the same panel of oligosaccharides as in (A). The concentrations of the P particles were 10 μg/ml, while oligosaccharides for plate coating at 2 μg/ml. Y axes indicate the binding signals in optical densities at 450 nm (OD450), while the X-axes indicate different oligosaccharides.

Mentions: We further investigated the roles of the eleven residues that form the HBGA binding interface of the OIF virus using single-point mutagenesis (Figs 5 and 6). Compared with the wild type P particle of OIF virus that binds strongly to Lea oligosaccharide, but not other oligosaccharides representing different HBGA types, including precursors (Fig 6A), mutant P particles with a single mutation at one of those amino acids to an alanine lost the binding to Lea antigen completely (Fig 6C–6L) or nearly completely (Fig 6B). These results confirmed the importance of these residues for the structural and functional integrity of the HBGA binding interface. In addition, except for a slight increase in binding to the A antigen of the E358A mutant, no changes in binding to other HBGA types were observed for these interface mutants.


A Unique Human Norovirus Lineage with a Distinct HBGA Binding Interface.

Liu W, Chen Y, Jiang X, Xia M, Yang Y, Tan M, Li X, Rao Z - PLoS Pathog. (2015)

HBGA-binding of wild type and various mutant P particles with single amino acid mutations at the HBGA-binding interface of OIF virus.(A), Binding of wild type OIF P particles with a panel of oligosaccharides representing different HBGAs (A, B, Lea, Leb, Lex, Ley, H1, H2, H3, sialyl Lea and sialyl Lex) and the type 1 (Pre1) and type 2 (Pre 2) precursors. (B to L), Binding of various mutant P particles with single amino acid mutations at the HBGA-binding interface with the same panel of oligosaccharides as in (A). The concentrations of the P particles were 10 μg/ml, while oligosaccharides for plate coating at 2 μg/ml. Y axes indicate the binding signals in optical densities at 450 nm (OD450), while the X-axes indicate different oligosaccharides.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4493018&req=5

ppat.1005025.g006: HBGA-binding of wild type and various mutant P particles with single amino acid mutations at the HBGA-binding interface of OIF virus.(A), Binding of wild type OIF P particles with a panel of oligosaccharides representing different HBGAs (A, B, Lea, Leb, Lex, Ley, H1, H2, H3, sialyl Lea and sialyl Lex) and the type 1 (Pre1) and type 2 (Pre 2) precursors. (B to L), Binding of various mutant P particles with single amino acid mutations at the HBGA-binding interface with the same panel of oligosaccharides as in (A). The concentrations of the P particles were 10 μg/ml, while oligosaccharides for plate coating at 2 μg/ml. Y axes indicate the binding signals in optical densities at 450 nm (OD450), while the X-axes indicate different oligosaccharides.
Mentions: We further investigated the roles of the eleven residues that form the HBGA binding interface of the OIF virus using single-point mutagenesis (Figs 5 and 6). Compared with the wild type P particle of OIF virus that binds strongly to Lea oligosaccharide, but not other oligosaccharides representing different HBGA types, including precursors (Fig 6A), mutant P particles with a single mutation at one of those amino acids to an alanine lost the binding to Lea antigen completely (Fig 6C–6L) or nearly completely (Fig 6B). These results confirmed the importance of these residues for the structural and functional integrity of the HBGA binding interface. In addition, except for a slight increase in binding to the A antigen of the E358A mutant, no changes in binding to other HBGA types were observed for these interface mutants.

Bottom Line: Each of the two major genogroups (GI and GII) of human NoVs recognizes a unique set of HBGAs through a distinct binding interface that is conserved within a genogroup, indicating a distinct evolutionary path for each genogroup.In addition, we found that glycerol inhibits OIF binding to HBGAs, potentially allowing production of cheap antivirals against human NoVs.Taken together, our results reveal a new evolutionary lineage of NoVs selected by HBGAs, a finding that is important for understanding the diversity and widespread nature of NoVs.

View Article: PubMed Central - PubMed

Affiliation: School of Life Sciences, University of Science and Technology of China, Hefei, Anhui, China.

ABSTRACT
Norovirus (NoV) causes epidemic acute gastroenteritis in humans, whereby histo-blood group antigens (HBGAs) play an important role in host susceptibility. Each of the two major genogroups (GI and GII) of human NoVs recognizes a unique set of HBGAs through a distinct binding interface that is conserved within a genogroup, indicating a distinct evolutionary path for each genogroup. Here, we characterize a Lewis a (Lea) antigen binding strain (OIF virus) in the GII.21 genotype that does not share the conserved GII binding interface, revealing a new evolution lineage with a distinct HBGA binding interface. Sequence alignment showed that the major residues contributing to the new HBGA binding interface are conserved among most members of the GII.21, as well as a closely related GII.13 genotype. In addition, we found that glycerol inhibits OIF binding to HBGAs, potentially allowing production of cheap antivirals against human NoVs. Taken together, our results reveal a new evolutionary lineage of NoVs selected by HBGAs, a finding that is important for understanding the diversity and widespread nature of NoVs.

No MeSH data available.


Related in: MedlinePlus