A Unique Human Norovirus Lineage with a Distinct HBGA Binding Interface.

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.

• Authors: Wu Liu, Yutao Chen, Xi Jiang, Ming Xia, Yang Yang, Ming Tan, Xuemei Li, Zihe Rao
• Journal: PLoS pathogens (PLoS Pathog) Vol. 11 Issue 7 Pg. e1005025 (Jul 2015) ISSN: 1553-7374 [Electronic] United States
• PMID: 26147716 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• Blood Group Antigens
• Viral Proteins

Topics

• Amino Acid Sequence
• Binding Sites (genetics)
• Biological Evolution
• Blood Group Antigens (metabolism)
• Crystallography, X-Ray
• Humans
• Molecular Sequence Data
• Mutagenesis, Site-Directed
• Norovirus (genetics)
• Phylogeny
• Protein Binding (genetics)
• Protein Conformation
• Viral Proteins (chemistry, genetics, metabolism)
• Virus Attachment