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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

Comparison of the seven major surface loops of OIF virus with those of five other GII noroviruses.Color schemes: cyan, OIF virus (GII.21); brown, VA387 (GII.4); yellow, VA207 (GII.9); purple, Vietnam026 (VN026, GII.10); green, Hiro (GII.12).
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ppat.1005025.g003: Comparison of the seven major surface loops of OIF virus with those of five other GII noroviruses.Color schemes: cyan, OIF virus (GII.21); brown, VA387 (GII.4); yellow, VA207 (GII.9); purple, Vietnam026 (VN026, GII.10); green, Hiro (GII.12).

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)

Comparison of the seven major surface loops of OIF virus with those of five other GII noroviruses.Color schemes: cyan, OIF virus (GII.21); brown, VA387 (GII.4); yellow, VA207 (GII.9); purple, Vietnam026 (VN026, GII.10); green, Hiro (GII.12).
© Copyright Policy
Related In: Results  -  Collection

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

ppat.1005025.g003: Comparison of the seven major surface loops of OIF virus with those of five other GII noroviruses.Color schemes: cyan, OIF virus (GII.21); brown, VA387 (GII.4); yellow, VA207 (GII.9); purple, Vietnam026 (VN026, GII.10); green, Hiro (GII.12).
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