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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

Structures (A) and the structure-based sequence alignment (B) of the P domains of OIF virus.(A), Overall structure (ribbon representation, green) of OIF P protein monomer (left) and its dimeric form (ribbon representation, green and pink) in complex with Lea trisaccharide (stick representation, indicated by arrows) (right). Secondary structural elements are labeled in the P monomer (left). (B), the structure-based sequence alignment of the P domains of GII.21 OIF, GII.4 VA387, GII.9 VA207, GII.10 VN026 and GII.12 Hiro. Regions spanning the P1 and P2 subdomains are indicated by arrows. Identical residues are highlighted with blue background, while similar residues are shown in red characters. Residues forming the HBGA binding interface of the GII.21 OIF are indicated in red frames, while the conserved amino acid residues forming the conventional GII HBGA binding interface are indicated by blue stars. The seven surface loops that constitute the two types of HBGA binding interfaces are indicated by black frames. The letters in blue backgrounds indicate the identical amino acid sequences, while the red letters indicate the similar amino acids among the five NoVs. Blue box fames both identical and similar residues.
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ppat.1005025.g002: Structures (A) and the structure-based sequence alignment (B) of the P domains of OIF virus.(A), Overall structure (ribbon representation, green) of OIF P protein monomer (left) and its dimeric form (ribbon representation, green and pink) in complex with Lea trisaccharide (stick representation, indicated by arrows) (right). Secondary structural elements are labeled in the P monomer (left). (B), the structure-based sequence alignment of the P domains of GII.21 OIF, GII.4 VA387, GII.9 VA207, GII.10 VN026 and GII.12 Hiro. Regions spanning the P1 and P2 subdomains are indicated by arrows. Identical residues are highlighted with blue background, while similar residues are shown in red characters. Residues forming the HBGA binding interface of the GII.21 OIF are indicated in red frames, while the conserved amino acid residues forming the conventional GII HBGA binding interface are indicated by blue stars. The seven surface loops that constitute the two types of HBGA binding interfaces are indicated by black frames. The letters in blue backgrounds indicate the identical amino acid sequences, while the red letters indicate the similar amino acids among the five NoVs. Blue box fames both identical and similar residues.

Mentions: The crystal of the native P domain protein belongs to the P21 space group, with two monomers forming a dimer in an asymmetric unit. The final refined structure of native P domain includes residues 223 to 527, with the exception of a loop region comprising residues 340~342 due to the lack of recognizable electron density. While the P domain of OIF virus shares only ~50% sequence homology with other GII P domains of known crystal structures, it shows an arrangement of overall and secondary structures similar to those huNoV P proteins, including GII.4 VA387 [20], GII.10 Vietnam 026 [23], GII.9 VA207 [21], and GII.12 Hiro [23] with Cα atoms r.m.s.d. = 0.85 Å, 0.83 Å, 0.82 Å, and 0.62 Å, respectively. Like other huNoVs, the OIF P domain has two moieties (Fig 2), with the inner portion or P1 subdomain (residues 223 to 272, and 416 to 527) constituting the leg, and the outer moiety or P2 subdomain (residues 273 to 415) forming the protruding head of the P dimer.


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)

Structures (A) and the structure-based sequence alignment (B) of the P domains of OIF virus.(A), Overall structure (ribbon representation, green) of OIF P protein monomer (left) and its dimeric form (ribbon representation, green and pink) in complex with Lea trisaccharide (stick representation, indicated by arrows) (right). Secondary structural elements are labeled in the P monomer (left). (B), the structure-based sequence alignment of the P domains of GII.21 OIF, GII.4 VA387, GII.9 VA207, GII.10 VN026 and GII.12 Hiro. Regions spanning the P1 and P2 subdomains are indicated by arrows. Identical residues are highlighted with blue background, while similar residues are shown in red characters. Residues forming the HBGA binding interface of the GII.21 OIF are indicated in red frames, while the conserved amino acid residues forming the conventional GII HBGA binding interface are indicated by blue stars. The seven surface loops that constitute the two types of HBGA binding interfaces are indicated by black frames. The letters in blue backgrounds indicate the identical amino acid sequences, while the red letters indicate the similar amino acids among the five NoVs. Blue box fames both identical and similar residues.
© Copyright Policy
Related In: Results  -  Collection

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ppat.1005025.g002: Structures (A) and the structure-based sequence alignment (B) of the P domains of OIF virus.(A), Overall structure (ribbon representation, green) of OIF P protein monomer (left) and its dimeric form (ribbon representation, green and pink) in complex with Lea trisaccharide (stick representation, indicated by arrows) (right). Secondary structural elements are labeled in the P monomer (left). (B), the structure-based sequence alignment of the P domains of GII.21 OIF, GII.4 VA387, GII.9 VA207, GII.10 VN026 and GII.12 Hiro. Regions spanning the P1 and P2 subdomains are indicated by arrows. Identical residues are highlighted with blue background, while similar residues are shown in red characters. Residues forming the HBGA binding interface of the GII.21 OIF are indicated in red frames, while the conserved amino acid residues forming the conventional GII HBGA binding interface are indicated by blue stars. The seven surface loops that constitute the two types of HBGA binding interfaces are indicated by black frames. The letters in blue backgrounds indicate the identical amino acid sequences, while the red letters indicate the similar amino acids among the five NoVs. Blue box fames both identical and similar residues.
Mentions: The crystal of the native P domain protein belongs to the P21 space group, with two monomers forming a dimer in an asymmetric unit. The final refined structure of native P domain includes residues 223 to 527, with the exception of a loop region comprising residues 340~342 due to the lack of recognizable electron density. While the P domain of OIF virus shares only ~50% sequence homology with other GII P domains of known crystal structures, it shows an arrangement of overall and secondary structures similar to those huNoV P proteins, including GII.4 VA387 [20], GII.10 Vietnam 026 [23], GII.9 VA207 [21], and GII.12 Hiro [23] with Cα atoms r.m.s.d. = 0.85 Å, 0.83 Å, 0.82 Å, and 0.62 Å, respectively. Like other huNoVs, the OIF P domain has two moieties (Fig 2), with the inner portion or P1 subdomain (residues 223 to 272, and 416 to 527) constituting the leg, and the outer moiety or P2 subdomain (residues 273 to 415) forming the protruding head of the P dimer.

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