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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

Sequence alignment of the surface loops of the P domains forming the HBGA-binding interfaces.Sequences of the six surface loops forming on the HBGA-binding interfaces representing the two genotypes of the GII.21 and GII.13, as well as GII.17, the genotype genetically close-relating to the GII.13/21 lineage, and GII.4 as a representative of the GII noroviruses (NoVs) with the conventional GII HBGA binding interfaces are aligned. The six surface loops that contribute to the formation of the two types of GII HBGA binding interfaces are labeled. The conserved residues forming the binding interface of OIF virus are shown in red fonts and labeled by red asterisks, while those forming the conventional GII binding interface are shown in blue fonts and labeled by blue asterisks. The GenBank accession numbers of P domain sequences are: AY675554 (OIF), AFC89665.1 (Sal), AY113106 (Fay), JN899242 (173), AY502009 (CSE), AY038600 (387).
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ppat.1005025.g008: Sequence alignment of the surface loops of the P domains forming the HBGA-binding interfaces.Sequences of the six surface loops forming on the HBGA-binding interfaces representing the two genotypes of the GII.21 and GII.13, as well as GII.17, the genotype genetically close-relating to the GII.13/21 lineage, and GII.4 as a representative of the GII noroviruses (NoVs) with the conventional GII HBGA binding interfaces are aligned. The six surface loops that contribute to the formation of the two types of GII HBGA binding interfaces are labeled. The conserved residues forming the binding interface of OIF virus are shown in red fonts and labeled by red asterisks, while those forming the conventional GII binding interface are shown in blue fonts and labeled by blue asterisks. The GenBank accession numbers of P domain sequences are: AY675554 (OIF), AFC89665.1 (Sal), AY113106 (Fay), JN899242 (173), AY502009 (CSE), AY038600 (387).

Mentions: The unique HBGA binding interface of the GII.21 OIF virus prompted us to examine whether this is a common feature of this specific huNoV lineage. Representative P domain sequences of GII.13/21 huNoVs were aligned and compared with those of GII.17, which is genetically closest to the GII.13/21 lineage (Fig 1A), as well as with that of GII.4, which is the most prevalent genotype. We focused on the surface loops that form the OIF HBGA binding pocket (B-, T, and N-loops) and the conventional GII binding interface (P-, S- and A-loops) (Fig 8). We found that most members of the GII.13/21 lineage share the major residues that form the novel HBGA binding pocket, indicating a new evolutionary selection has occurred among members of this genetic lineage. In contrast, GII.17 retained the conventional GII HBGA binding interfaces, indicating that the occurrence of the OIF-like binding pocket in the GII.13/21 lineage was after the evolutionary divergence with the GII.17 genotype.


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)

Sequence alignment of the surface loops of the P domains forming the HBGA-binding interfaces.Sequences of the six surface loops forming on the HBGA-binding interfaces representing the two genotypes of the GII.21 and GII.13, as well as GII.17, the genotype genetically close-relating to the GII.13/21 lineage, and GII.4 as a representative of the GII noroviruses (NoVs) with the conventional GII HBGA binding interfaces are aligned. The six surface loops that contribute to the formation of the two types of GII HBGA binding interfaces are labeled. The conserved residues forming the binding interface of OIF virus are shown in red fonts and labeled by red asterisks, while those forming the conventional GII binding interface are shown in blue fonts and labeled by blue asterisks. The GenBank accession numbers of P domain sequences are: AY675554 (OIF), AFC89665.1 (Sal), AY113106 (Fay), JN899242 (173), AY502009 (CSE), AY038600 (387).
© Copyright Policy
Related In: Results  -  Collection

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

ppat.1005025.g008: Sequence alignment of the surface loops of the P domains forming the HBGA-binding interfaces.Sequences of the six surface loops forming on the HBGA-binding interfaces representing the two genotypes of the GII.21 and GII.13, as well as GII.17, the genotype genetically close-relating to the GII.13/21 lineage, and GII.4 as a representative of the GII noroviruses (NoVs) with the conventional GII HBGA binding interfaces are aligned. The six surface loops that contribute to the formation of the two types of GII HBGA binding interfaces are labeled. The conserved residues forming the binding interface of OIF virus are shown in red fonts and labeled by red asterisks, while those forming the conventional GII binding interface are shown in blue fonts and labeled by blue asterisks. The GenBank accession numbers of P domain sequences are: AY675554 (OIF), AFC89665.1 (Sal), AY113106 (Fay), JN899242 (173), AY502009 (CSE), AY038600 (387).
Mentions: The unique HBGA binding interface of the GII.21 OIF virus prompted us to examine whether this is a common feature of this specific huNoV lineage. Representative P domain sequences of GII.13/21 huNoVs were aligned and compared with those of GII.17, which is genetically closest to the GII.13/21 lineage (Fig 1A), as well as with that of GII.4, which is the most prevalent genotype. We focused on the surface loops that form the OIF HBGA binding pocket (B-, T, and N-loops) and the conventional GII binding interface (P-, S- and A-loops) (Fig 8). We found that most members of the GII.13/21 lineage share the major residues that form the novel HBGA binding pocket, indicating a new evolutionary selection has occurred among members of this genetic lineage. In contrast, GII.17 retained the conventional GII HBGA binding interfaces, indicating that the occurrence of the OIF-like binding pocket in the GII.13/21 lineage was after the evolutionary divergence with the GII.17 genotype.

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