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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

Glycerol binds the HBGA binding interface of OIF virus.(A), (Fo-Fc) omit electron density map of glycerol. The omit map was created and contoured as described in Fig 5A. (B and C), The interacting networks between the side chains of the amino acids of the HBGA binding interface of OIF virus with the glycerol molecule. The hydrogen bonds are indicated by dashed lines. Carbon, oxygen and nitrogen atoms are in cyan, red and blue, respectively. (D) Blocking effects of monomeric glycerol (0–10%, X-axis) against the binding (Y-axis) of the polyvalent Lea-tri-PAA (polyacrylamide) conjugates (2 μg/mL) to OIF P particles (4 μg/mL) via ELISA-based blocking assays.
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ppat.1005025.g007: Glycerol binds the HBGA binding interface of OIF virus.(A), (Fo-Fc) omit electron density map of glycerol. The omit map was created and contoured as described in Fig 5A. (B and C), The interacting networks between the side chains of the amino acids of the HBGA binding interface of OIF virus with the glycerol molecule. The hydrogen bonds are indicated by dashed lines. Carbon, oxygen and nitrogen atoms are in cyan, red and blue, respectively. (D) Blocking effects of monomeric glycerol (0–10%, X-axis) against the binding (Y-axis) of the polyvalent Lea-tri-PAA (polyacrylamide) conjugates (2 μg/mL) to OIF P particles (4 μg/mL) via ELISA-based blocking assays.

Mentions: Analysis of the native OIF P domain structure revealed that a glycerol molecule occupies the HBGA binding pocket, which was clearly visible from the 2Fo-Fc omit map (Fig 7A). Originally, glycerol was part of the protease solution acting as a stabilizer during the cleavage of the GST-P domain fusion protein. The glycerol molecule is held firmly inside the HBGA binding pocket by eight direct hydrogen bonds between the hydroxyl groups of the glycerol and the side chains of N392, N394 and T395 from the T-loop, T356 and the main chain of S357 from the N-loop (Fig 7B and 7C). Interestingly, the glycerol molecule resembles partial structures (C2, C3, and C4 with their hydroxyl groups) of the β-Gal that contributes the vast majority of the interactions with the binding pocket (Compare Fig 5F with Fig 7C), thus explaining the observed interactions.


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)

Glycerol binds the HBGA binding interface of OIF virus.(A), (Fo-Fc) omit electron density map of glycerol. The omit map was created and contoured as described in Fig 5A. (B and C), The interacting networks between the side chains of the amino acids of the HBGA binding interface of OIF virus with the glycerol molecule. The hydrogen bonds are indicated by dashed lines. Carbon, oxygen and nitrogen atoms are in cyan, red and blue, respectively. (D) Blocking effects of monomeric glycerol (0–10%, X-axis) against the binding (Y-axis) of the polyvalent Lea-tri-PAA (polyacrylamide) conjugates (2 μg/mL) to OIF P particles (4 μg/mL) via ELISA-based blocking assays.
© Copyright Policy
Related In: Results  -  Collection

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

ppat.1005025.g007: Glycerol binds the HBGA binding interface of OIF virus.(A), (Fo-Fc) omit electron density map of glycerol. The omit map was created and contoured as described in Fig 5A. (B and C), The interacting networks between the side chains of the amino acids of the HBGA binding interface of OIF virus with the glycerol molecule. The hydrogen bonds are indicated by dashed lines. Carbon, oxygen and nitrogen atoms are in cyan, red and blue, respectively. (D) Blocking effects of monomeric glycerol (0–10%, X-axis) against the binding (Y-axis) of the polyvalent Lea-tri-PAA (polyacrylamide) conjugates (2 μg/mL) to OIF P particles (4 μg/mL) via ELISA-based blocking assays.
Mentions: Analysis of the native OIF P domain structure revealed that a glycerol molecule occupies the HBGA binding pocket, which was clearly visible from the 2Fo-Fc omit map (Fig 7A). Originally, glycerol was part of the protease solution acting as a stabilizer during the cleavage of the GST-P domain fusion protein. The glycerol molecule is held firmly inside the HBGA binding pocket by eight direct hydrogen bonds between the hydroxyl groups of the glycerol and the side chains of N392, N394 and T395 from the T-loop, T356 and the main chain of S357 from the N-loop (Fig 7B and 7C). Interestingly, the glycerol molecule resembles partial structures (C2, C3, and C4 with their hydroxyl groups) of the β-Gal that contributes the vast majority of the interactions with the binding pocket (Compare Fig 5F with Fig 7C), thus explaining the observed interactions.

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