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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

Evolutionary changes of the topologies of the P dimer top surface of OIF compared with other noroviruses.(A), GII.21 OIF virus; (B), GII.4 VA387 (387); (C), GII.9 VA207 (207); (D), GII.10 Vietnam026 (VN026); (E), GII.12 Hiro; (F), GI.1 Norwalk virus (NV). The seven major surface loops, i.e. A-, B-, P-, S-, T-, U-, and N-loops are indicated in light-green, orange, cyan, purple, dark-green, red, and blue, respectively. The locations of the HBGA binding interfaces are indicated by yellow dashed circles. (G and H), Comparison of the top surface structures of the P dimers of OIF virus (G) and VA387 (H). The two P protomers are labeled in grey and sand colors. Bound HBGAs are shown in stick representation, with the major binding saccharide (galactose in OIF, fucose in VA387) colored in yellow.
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ppat.1005025.g004: Evolutionary changes of the topologies of the P dimer top surface of OIF compared with other noroviruses.(A), GII.21 OIF virus; (B), GII.4 VA387 (387); (C), GII.9 VA207 (207); (D), GII.10 Vietnam026 (VN026); (E), GII.12 Hiro; (F), GI.1 Norwalk virus (NV). The seven major surface loops, i.e. A-, B-, P-, S-, T-, U-, and N-loops are indicated in light-green, orange, cyan, purple, dark-green, red, and blue, respectively. The locations of the HBGA binding interfaces are indicated by yellow dashed circles. (G and H), Comparison of the top surface structures of the P dimers of OIF virus (G) and VA387 (H). The two P protomers are labeled in grey and sand colors. Bound HBGAs are shown in stick representation, with the major binding saccharide (galactose in OIF, fucose in VA387) colored in yellow.

Mentions: The two monomers of the OIF P dimer are related by a non-crystallographic two-fold axis, which forms the biologically active protrusion of the NoV capsid. The P dimer has a dimension of 55 Å×64 Å×70 Å with an extensively buried interface of 3,500 Å2 between two protomers, including hydrophobic and hydrophilic interacting residues from both P1 and P2 subdomains (Fig 2A). These extensive inter-molecular interactions contribute to the stability of the P dimer. Although the OIF P dimer shares similar global structures with the previously reported P dimers of other huNoVs, significant differences on the top surface are clearly seen, mainly due to the differences in the sequences, lengths, and conformations of several surface loops (Figs 3 and 4) (see below).


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)

Evolutionary changes of the topologies of the P dimer top surface of OIF compared with other noroviruses.(A), GII.21 OIF virus; (B), GII.4 VA387 (387); (C), GII.9 VA207 (207); (D), GII.10 Vietnam026 (VN026); (E), GII.12 Hiro; (F), GI.1 Norwalk virus (NV). The seven major surface loops, i.e. A-, B-, P-, S-, T-, U-, and N-loops are indicated in light-green, orange, cyan, purple, dark-green, red, and blue, respectively. The locations of the HBGA binding interfaces are indicated by yellow dashed circles. (G and H), Comparison of the top surface structures of the P dimers of OIF virus (G) and VA387 (H). The two P protomers are labeled in grey and sand colors. Bound HBGAs are shown in stick representation, with the major binding saccharide (galactose in OIF, fucose in VA387) colored in yellow.
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4493018&req=5

ppat.1005025.g004: Evolutionary changes of the topologies of the P dimer top surface of OIF compared with other noroviruses.(A), GII.21 OIF virus; (B), GII.4 VA387 (387); (C), GII.9 VA207 (207); (D), GII.10 Vietnam026 (VN026); (E), GII.12 Hiro; (F), GI.1 Norwalk virus (NV). The seven major surface loops, i.e. A-, B-, P-, S-, T-, U-, and N-loops are indicated in light-green, orange, cyan, purple, dark-green, red, and blue, respectively. The locations of the HBGA binding interfaces are indicated by yellow dashed circles. (G and H), Comparison of the top surface structures of the P dimers of OIF virus (G) and VA387 (H). The two P protomers are labeled in grey and sand colors. Bound HBGAs are shown in stick representation, with the major binding saccharide (galactose in OIF, fucose in VA387) colored in yellow.
Mentions: The two monomers of the OIF P dimer are related by a non-crystallographic two-fold axis, which forms the biologically active protrusion of the NoV capsid. The P dimer has a dimension of 55 Å×64 Å×70 Å with an extensively buried interface of 3,500 Å2 between two protomers, including hydrophobic and hydrophilic interacting residues from both P1 and P2 subdomains (Fig 2A). These extensive inter-molecular interactions contribute to the stability of the P dimer. Although the OIF P dimer shares similar global structures with the previously reported P dimers of other huNoVs, significant differences on the top surface are clearly seen, mainly due to the differences in the sequences, lengths, and conformations of several surface loops (Figs 3 and 4) (see below).

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