Trends in Microbiology
OpinionNorovirus–host interaction: Multi-selections by human histo-blood group antigens
Section snippets
Norovirus–host cell interactions
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 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12. HBGAs are complex carbohydrates on red blood cells, mucosal epithelia, saliva, milk and other body fluids, which are highly
Multi-interaction network between NoVs and HBGAs
The Norwalk virus (GI.1), NoV VA387 (GII.4) and NoV VA207 (GII.9) represent three major HBGA binding patterns 5, 6 and three genotypes in genogroups I and II (GI and GII). The HBGA binding interfaces of these three NoVs have been resolved by co-crystallization of the P domains of the viral capsid in complex with corresponding HBGA oligosaccharides 17, 18, 19, 20. All three NoVs revealed two symmetric HBGA binding interfaces on each arch-like P dimer, corresponding to the outermost surface of
A model of NoV–HBGA interaction
The majority of human blood types, including the secretor, ABO and Lewis blood types are determined by three unique types of saccharides (Figure 2a). The α-1,2 Fuc (H epitope) is the determinant of the secretor blood type; this saccharide is added to the precursor of the HBGAs by the α-1,2 fucosyl transferase encoded by FUT2. The two saccharides, α-GalNAc and α-Gal (the A/B epitopes), are the determinants for the A/B blood types and are added to the H antigen by the A/B enzymes, respectively.
Conservation of binding interfaces
Sequence alignments of the P domain showed that the amino acid compositions of the HBGA binding interfaces are highly conserved among strains within but not between the two major genogroups (GI and GII) of human NoVs [30]. All eight genotypes of GI share similar residue composition of binding interfaces with the Norwalk virus, in which D327, H329, W375, S377 and S378 (numbered according to Norwalk virus) are highly conserved, whereas Q342 and D344 are modestly conserved [30]. Similarly, all 17
Implications for evolution of NoVs
The high conservation of the HBGA binding interfaces indicates an important role of human HBGAs in NoV evolution. The segregation of the primary sequences of the genomes, the difference of overall structures of the capsids, and the distinct structures, amino acid compositions and binding modes of the HBGA binding interfaces between GI and GII strongly suggest that these two genogroups were two species that might have developed their HBGA binding ability independently either prior to or once
Implications for epidemiology
The structural basis of the NoV–HBGA interaction and its implication in evolution of NoVs provides new insights into the epidemiology of human NoVs. First, the separation of the two genogroups into two independent species (lineages) highlights their difference in genetic make-up, biological properties and thus epidemiological outcomes. The GI NoVs are more frequently detected in environmental contamination than the GII NoVs, such as in waste water 44, 45. However, the GII NoVs cause the
Concluding remarks
The crystal structure analysis of the NoV P domain–HBGA complex has led to the elucidation of the interaction between NoVs and variable HBGAs. Further sequence comparison in combination with phylogenetic analysis has resulted in the discovery of high conservation of the HBGA binding interfaces and segregation of two binding interfaces in the two genogroups of human NoVs. These new advances have led to the concept of convergent evolution of NoVs via selection by human HBGAs. This new concept
Acknowledgments
We thank Dr Yutao Chen from the Institute of Biophysics, Chinese Academic of Sciences for help in preparing the figures. The research in Tan and Jiang's laboratory was supported by the National Institute of Health, the National Institute of Allergy and Infectious Diseases (R01 AI37093, R01 AI055649 and R01 AI089634), the Department of Defense (PR033018) to X.J. and by an Institutional Clinical and Translational Science Award, NIH/NCRR Grant Number 1UL1RR026314-01 to M.T.
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