title: 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.affiliation: School of Life Sciences, University of Science and Technology of China, Hefei, Anhui, China.
authors.forename: Wu
authors.initials: W
authors.lastname: Liu
authors.affiliation: National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.
authors.forename: Yutao
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Division of Infectious Diseases, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio United States of America; University of Cincinnati College of Medicine, Cincinnati, Ohio, United States of America.
authors.forename: Xi
authors.initials: X
authors.lastname: Jiang
authors.affiliation: Division of Infectious Diseases, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio United States of America.
authors.forename: Ming
authors.initials: M
authors.lastname: Xia
authors.affiliation: National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Division of Infectious Diseases, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio United States of America; University of Cincinnati College of Medicine, Cincinnati, Ohio, United States of America.
authors.forename: Ming
authors.initials: M
authors.lastname: Tan
authors.affiliation: National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.
authors.forename: Xuemei
authors.initials: X
authors.lastname: Li
authors.affiliation: National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.
authors.forename: Zihe
authors.initials: Z
authors.lastname: Rao
mesh_terms: D000595:Amino Acid Sequence; D001665:Binding Sites / Q000235:genetics; D005075:Biological Evolution; D001789:Blood Group Antigens / Q000378:metabolism*; D018360:Crystallography, X-Ray; D006801:Humans; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D029322:Norovirus / Q000235:genetics*; D010802:Phylogeny; D011485:Protein Binding / Q000235:genetics; D011487:Protein Conformation; D014764:Viral Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D053585:Virus Attachment
chemical_list: D001789:Blood Group Antigens; D014764:Viral Proteins