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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

Phylogenetic and sequence analysis of genogroup (G) II noroviruses (NoVs).(A), Phylogenetic tree of GII NoVs that is re-drawn according to [52]. The unique genetic branch consisting of GII.13 and GII.21 genotypes is indicated by a green frame. (B), P domain sequence alignment of NoVs representing each of the 20 GII genotypes with a focus on the residues at the HBGA binding interface. The conserved amino acids constituting the GII conventional HBGA binding interface are indicated with colored letter in frames. The GenBank accession numbers of the P domain sequences are: AY038600.3 (VA387), U07611 (Hawaii), AY134748 (SMV), U22498 (Mexico), X86557 (Lordsdale), AF397156 (MOH), AF414407 (Florida269), AJ277608 (Leeds), AF195848 (Amsterdam), AAK84676 (VA207), AF427118 (Erfurt), AB074893 (SW918), AJ277618 (Wortley), AY113106 (Fayettevil), AY130761 (M7), AY130762 (J23), AY502010 (Tiffin), AY502009 (CS-E1), AY823304 (SW101), AY823306 (SW170), EU373815 (Lucken), AY675554 (OIF), and AB083780.1 (YURI).
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ppat.1005025.g001: Phylogenetic and sequence analysis of genogroup (G) II noroviruses (NoVs).(A), Phylogenetic tree of GII NoVs that is re-drawn according to [52]. The unique genetic branch consisting of GII.13 and GII.21 genotypes is indicated by a green frame. (B), P domain sequence alignment of NoVs representing each of the 20 GII genotypes with a focus on the residues at the HBGA binding interface. The conserved amino acids constituting the GII conventional HBGA binding interface are indicated with colored letter in frames. The GenBank accession numbers of the P domain sequences are: AY038600.3 (VA387), U07611 (Hawaii), AY134748 (SMV), U22498 (Mexico), X86557 (Lordsdale), AF397156 (MOH), AF414407 (Florida269), AJ277608 (Leeds), AF195848 (Amsterdam), AAK84676 (VA207), AF427118 (Erfurt), AB074893 (SW918), AJ277618 (Wortley), AY113106 (Fayettevil), AY130761 (M7), AY130762 (J23), AY502010 (Tiffin), AY502009 (CS-E1), AY823304 (SW101), AY823306 (SW170), EU373815 (Lucken), AY675554 (OIF), and AB083780.1 (YURI).

Mentions: Structural analysis of known HBGA binding interfaces of huNoVs showed that GI and GII huNoVs recognize HBGAs through a conserved, genogroup-specific binding interface (reviewed in [27–29]), suggesting a strong selection of huNoV evolution by human HBGAs. On the other hand, the GI and GII HBGA-binding interfaces are distinct in the locations, structures, residue compositions, and HBGA binding modes [27–29], indicating a long separation of the two genetic lineages. In this study we report a new evolutionary lineage consisting of GII.13 and GII.21 genotypes within GII, which does not share the conventional GII HBGA binding interface (Fig 1), but remains binding ability to HBGAs [5, 30]. X-ray crystallography of the GII.21 OIF virus P domain complexed with a Lea antigen revealed a new HBGA binding interface that is distinct from the GII conventional binding interface. Sequence alignment further showed that the amino acid composition of the new binding interface of OIF is highly conserved among all members of both GII.21 and a closely related GII.13 genotype. These results indicate that the genetic branch consisting of GII.21 and GII.13 developed along a novel evolutionary path that split from the mainstream lineage of GII NoVs selected by HBGAs. While many questions on the cause and mechanisms behind the emergence of this new lineage remain unanswered, our data point towards a continual occurrence of new lineages, which may significantly impact future epidemiology and prevention strategies against huNoVs.


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)

Phylogenetic and sequence analysis of genogroup (G) II noroviruses (NoVs).(A), Phylogenetic tree of GII NoVs that is re-drawn according to [52]. The unique genetic branch consisting of GII.13 and GII.21 genotypes is indicated by a green frame. (B), P domain sequence alignment of NoVs representing each of the 20 GII genotypes with a focus on the residues at the HBGA binding interface. The conserved amino acids constituting the GII conventional HBGA binding interface are indicated with colored letter in frames. The GenBank accession numbers of the P domain sequences are: AY038600.3 (VA387), U07611 (Hawaii), AY134748 (SMV), U22498 (Mexico), X86557 (Lordsdale), AF397156 (MOH), AF414407 (Florida269), AJ277608 (Leeds), AF195848 (Amsterdam), AAK84676 (VA207), AF427118 (Erfurt), AB074893 (SW918), AJ277618 (Wortley), AY113106 (Fayettevil), AY130761 (M7), AY130762 (J23), AY502010 (Tiffin), AY502009 (CS-E1), AY823304 (SW101), AY823306 (SW170), EU373815 (Lucken), AY675554 (OIF), and AB083780.1 (YURI).
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Related In: Results  -  Collection

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ppat.1005025.g001: Phylogenetic and sequence analysis of genogroup (G) II noroviruses (NoVs).(A), Phylogenetic tree of GII NoVs that is re-drawn according to [52]. The unique genetic branch consisting of GII.13 and GII.21 genotypes is indicated by a green frame. (B), P domain sequence alignment of NoVs representing each of the 20 GII genotypes with a focus on the residues at the HBGA binding interface. The conserved amino acids constituting the GII conventional HBGA binding interface are indicated with colored letter in frames. The GenBank accession numbers of the P domain sequences are: AY038600.3 (VA387), U07611 (Hawaii), AY134748 (SMV), U22498 (Mexico), X86557 (Lordsdale), AF397156 (MOH), AF414407 (Florida269), AJ277608 (Leeds), AF195848 (Amsterdam), AAK84676 (VA207), AF427118 (Erfurt), AB074893 (SW918), AJ277618 (Wortley), AY113106 (Fayettevil), AY130761 (M7), AY130762 (J23), AY502010 (Tiffin), AY502009 (CS-E1), AY823304 (SW101), AY823306 (SW170), EU373815 (Lucken), AY675554 (OIF), and AB083780.1 (YURI).
Mentions: Structural analysis of known HBGA binding interfaces of huNoVs showed that GI and GII huNoVs recognize HBGAs through a conserved, genogroup-specific binding interface (reviewed in [27–29]), suggesting a strong selection of huNoV evolution by human HBGAs. On the other hand, the GI and GII HBGA-binding interfaces are distinct in the locations, structures, residue compositions, and HBGA binding modes [27–29], indicating a long separation of the two genetic lineages. In this study we report a new evolutionary lineage consisting of GII.13 and GII.21 genotypes within GII, which does not share the conventional GII HBGA binding interface (Fig 1), but remains binding ability to HBGAs [5, 30]. X-ray crystallography of the GII.21 OIF virus P domain complexed with a Lea antigen revealed a new HBGA binding interface that is distinct from the GII conventional binding interface. Sequence alignment further showed that the amino acid composition of the new binding interface of OIF is highly conserved among all members of both GII.21 and a closely related GII.13 genotype. These results indicate that the genetic branch consisting of GII.21 and GII.13 developed along a novel evolutionary path that split from the mainstream lineage of GII NoVs selected by HBGAs. While many questions on the cause and mechanisms behind the emergence of this new lineage remain unanswered, our data point towards a continual occurrence of new lineages, which may significantly impact future epidemiology and prevention strategies against huNoVs.

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