Noroviruses (NoVs) are a major cause of epidemic acute gastroenteritis affecting millions of people worldwide. Infection by NoVs relies on recognition of human histo-blood group antigens (HBGAs) as ligands or receptors for attachment, an early infection event that most likely controls host susceptibility and resistance to NoVs. HBGAs are complex carbohydrates on red blood cells, mucosal epithelia, saliva, milk and other body fluids, which are highly polymorphic and are related to the ABO, secretor and Lewis families. The interaction between NoVs and HBGAs has been extensively studied since it was discovered in 2002. Early studies using variable in vitro binding assays to measure the binding of NoV-like particles (VLPs) with HBGAs revealed diverse binding patterns. Further studies in human volunteer challenge and outbreak investigations provided direct evidence on the linkage between host blood types and susceptibility to NoV infection and, therefore, implicated HBGAs as NoV receptors or co-receptors, although undefined results were also reported.
Recent structural and functional analysis of the HBGA binding interfaces of NoVs has significantly advanced our understanding of the complicated interaction between NoVs and human HBGAs. For the first time, crystal structures of the HBGA binding interfaces of representative NoVs in complex with different HBGAs precisely elucidated interactions between individual amino acids in the binding interfaces of NoVs with specific saccharides of HBGAs. This article summarizes these advancements, proposes a new model of NoV–HBGA interaction, and discusses the role of HBGAs in NoV evolution and the resulting impacts on epidemiology and classification of human NoVs.
Norovirus-host interaction: Multi-selections by human histo-blood group antigens. Trends Microbiol. Jun 24 2011
The discovery of human histo-blood group antigens (HBGAs) as receptors or ligands of noroviruses (NoVs) raises a question about the potential role of host factors in the evolution and diversity of NoVs. Recent structural analysis of selected strains in the two major genogroups of human NoVs (GI and GII) demonstrated highly conserved HBGA binding interfaces within the two groups but not between them, indicating convergent evolution of GI and GII NoVs. GI and GII NoVs are probably introduced to humans from different non-human hosts with the HBGAs as a common niche. Each genogroup has further diverged into multiple sub-lineages (genotypes) through selections by the polymorphic HBGAs of the hosts. An elucidation of such pathogen–host interaction, including determination of the phenotypes of NoV–HBGAs interaction for each genotype, is important in understanding the epidemiology, classification and disease control and prevention of NoVs. A model of this multi-selection of NoVs by HBGAs is proposed.