A Unique Human Norovirus Lineage with a Distinct HBGA Binding Interface

PLoS Pathogens

Xuemei Li¹  Xi Jiang¹  Yang Yang¹  Yutao Chen²  Ming Tan²  Wu Liu³  Zihe Rao⁴  Ming Xia⁴ 

[1] Division of Infectious Diseases, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio United States of America;National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China;School of Life Sciences, University of Science and Technology of China, Hefei, Anhui, China;University of Cincinnati College of Medicine, Cincinnati, Ohio, United States of America

关键词: Glycerol;    Crystal structure;    Dimers (Chemical physics);    Viral evolution;    Hydrogen bonding;    Viral structure;    Evolutionary genetics;    Sequence alignment;   

DOI  :  10.1371/journal.ppat.1005025

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

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.

【 授权许可】

CC BY