Avidity of α-fucose on human milk oligosaccharides and blood group-unrelated oligo/polyfucoses is essential for potent norovirus-binding targets
There is agreement with respect to norovirus infection routes in humans regarding binding of the pathogen to gastrointestinal epithelia via recognition of blood group-active mucin-typeO-glycans as the initiating and essential event. Among food additives playing a potential role in applications to pr...
Saved in:
| Main Authors: | , , , |
|---|---|
| Format: | Article (Journal) |
| Language: | English |
| Published: |
June 1, 2018
|
| In: |
The journal of biological chemistry
Year: 2018, Volume: 293, Issue: 30, Pages: 11955-11965 |
| ISSN: | 1083-351X |
| DOI: | 10.1074/jbc.RA117.001369 |
| Online Access: | Verlag, kostenfrei, Volltext: http://dx.doi.org/10.1074/jbc.RA117.001369 Verlag, kostenfrei, Volltext: http://www.jbc.org/content/293/30/11955 
|
| Author Notes: | Franz-Georg Hanisch, Grant S. Hansman, Vasily Morozov, Clemens Kunz, Horst Schroten |
| Summary: | There is agreement with respect to norovirus infection routes in humans regarding binding of the pathogen to gastrointestinal epithelia via recognition of blood group-active mucin-typeO-glycans as the initiating and essential event. Among food additives playing a potential role in applications to protect newborns, human milk oligosaccharides (HMOs) as competitors are of major importance. By focusing on fractions of high-molecular mass HMOs with high fucose contents, we attempted to identify the structural elements required for norovirus GII.4 (Sydney 2012, JX459908) capsid binding in neoglycolipid-based arrays. We provide evidence that HMO fractions with the strongest binding capacities contained hepta- to decasaccharides expressing branches with terminal blood group H1 or Lewis-b antigen. H2 antigen, as recognized by UEA-I lectin, is apparently not expressed in high-mass HMOs. Beyond affinity, sterical and valency effects contribute more to virus-like particle binding, as revealed for oligovalent fucose conjugates of α-cyclodextrin and oligofucoses from fucoidan. Accordingly, high-mass HMOs with oligovalent fucose can exhibit stronger binding capacities compared with monovalent fucose HMOs. The above features were revealed for the most clinically relevant and prevalent GII.4 strain and are distinct from other strains, like GII.10 (Vietnam 026, AF504671), which showed a preference for blood group Lewis-a positive glycans. |
|---|---|
| Item Description: | Gesehen am 09.08.2018 |
| Physical Description: | Online Resource |
| ISSN: | 1083-351X |
| DOI: | 10.1074/jbc.RA117.001369 |