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Carbohydrate recognition in the immune system: contributions of neoglycolipid-based microarrays to carbohydrate ligand discovery.

Feizi T - Ann. N. Y. Acad. Sci. (2013)

Bottom Line: The pinpointing and characterizing of oligosaccharide ligands within glycomes has been one of the most challenging aspects of molecular cell biology, as oligosaccharides cannot be cloned and are generally available in limited amounts.This overview recounts the background to the development of a microarray system that is poised for surveying proteomes for carbohydrate-binding activities and glycomes for assigning the oligosaccharide ligands.Particularly highlighted are sulfo-oligosaccharide and gluco-oligosaccharide recognition systems elucidated using microarrays.

View Article: PubMed Central - PubMed

Affiliation: The Glycosciences Laboratory, Department of Medicine, Imperial College London, London, United Kingdom. t.feizi@imperial.ac.uk

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Related in: MedlinePlus

Highlights of microarray analyses of pandemic influenza A(H1N1) 2009 (pdm) viruses showing wild-type (222D) pdm viruses binding to α2,3 sialyl sequences with sulphate or fucose at penultimate N-acetylglucosamine, and mutant (222G) viruses increased binding to these and also binding to unmodified or internally fucosylated (VIM-2) sequences. The latter are known to be expressed on ciliated epithelial cells of the human bronchus (adapted from Refs. 56 and 57).
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fig06: Highlights of microarray analyses of pandemic influenza A(H1N1) 2009 (pdm) viruses showing wild-type (222D) pdm viruses binding to α2,3 sialyl sequences with sulphate or fucose at penultimate N-acetylglucosamine, and mutant (222G) viruses increased binding to these and also binding to unmodified or internally fucosylated (VIM-2) sequences. The latter are known to be expressed on ciliated epithelial cells of the human bronchus (adapted from Refs. 56 and 57).

Mentions: With the NGL-based microarray system, we have also observed an influence of sulfation of sialyl oligosaccharides on receptor-binding by the pandemic influenza A(H1N1) 2009 (pdm) virus.56,57 Although, as with seasonal influenza viruses, the strongest binding, overall, of the pdm viruses was to α2,6-linked sialyl sequences that are abundantly expressed in the upper respiratory tract, we detected binding of pdm viruses also to α2,3-linked sialyl sequences with sulfate (or fucose) at penultimate N-acetylglucosamine of the type that occur lower down in the respiratory tract (Fig. 6). The intensity of binding to these was enhanced with mutant viruses (D222G mutation of hemagglutinin) isolated from cases of severe or fatal pdm virus infection: with the D222G mutant pdm viruses there was binding also to nonsulfated internally fucosylated (VIM-2 antigen-bearing) sequences of the type expressed on ciliated cells of the bronchus (Fig. 6).57 The D222G mutant pdm viruses showed a change in cell tropism in cultures of differentiated human airway epithelial cells; they infected a higher proportion of ciliated epithelial cells than the wild-type pdm viruses. The additional binding of pdm viruses to α2–3 sialyl sequences that occur throughout the airway, including the lung, may account, at least in part, for the capacity of the pdm viruses to cause more severe disease than observed with seasonal influenza. These findings uncover potential mechanisms linking mutation D222G to severity of disease. If the mutant virus were to acquire the ability to spread more widely, the potential consequences would be of great significance, hence the need to closely monitor the evolution of this virus.


Carbohydrate recognition in the immune system: contributions of neoglycolipid-based microarrays to carbohydrate ligand discovery.

Feizi T - Ann. N. Y. Acad. Sci. (2013)

Highlights of microarray analyses of pandemic influenza A(H1N1) 2009 (pdm) viruses showing wild-type (222D) pdm viruses binding to α2,3 sialyl sequences with sulphate or fucose at penultimate N-acetylglucosamine, and mutant (222G) viruses increased binding to these and also binding to unmodified or internally fucosylated (VIM-2) sequences. The latter are known to be expressed on ciliated epithelial cells of the human bronchus (adapted from Refs. 56 and 57).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4260124&req=5

fig06: Highlights of microarray analyses of pandemic influenza A(H1N1) 2009 (pdm) viruses showing wild-type (222D) pdm viruses binding to α2,3 sialyl sequences with sulphate or fucose at penultimate N-acetylglucosamine, and mutant (222G) viruses increased binding to these and also binding to unmodified or internally fucosylated (VIM-2) sequences. The latter are known to be expressed on ciliated epithelial cells of the human bronchus (adapted from Refs. 56 and 57).
Mentions: With the NGL-based microarray system, we have also observed an influence of sulfation of sialyl oligosaccharides on receptor-binding by the pandemic influenza A(H1N1) 2009 (pdm) virus.56,57 Although, as with seasonal influenza viruses, the strongest binding, overall, of the pdm viruses was to α2,6-linked sialyl sequences that are abundantly expressed in the upper respiratory tract, we detected binding of pdm viruses also to α2,3-linked sialyl sequences with sulfate (or fucose) at penultimate N-acetylglucosamine of the type that occur lower down in the respiratory tract (Fig. 6). The intensity of binding to these was enhanced with mutant viruses (D222G mutation of hemagglutinin) isolated from cases of severe or fatal pdm virus infection: with the D222G mutant pdm viruses there was binding also to nonsulfated internally fucosylated (VIM-2 antigen-bearing) sequences of the type expressed on ciliated cells of the bronchus (Fig. 6).57 The D222G mutant pdm viruses showed a change in cell tropism in cultures of differentiated human airway epithelial cells; they infected a higher proportion of ciliated epithelial cells than the wild-type pdm viruses. The additional binding of pdm viruses to α2–3 sialyl sequences that occur throughout the airway, including the lung, may account, at least in part, for the capacity of the pdm viruses to cause more severe disease than observed with seasonal influenza. These findings uncover potential mechanisms linking mutation D222G to severity of disease. If the mutant virus were to acquire the ability to spread more widely, the potential consequences would be of great significance, hence the need to closely monitor the evolution of this virus.

Bottom Line: The pinpointing and characterizing of oligosaccharide ligands within glycomes has been one of the most challenging aspects of molecular cell biology, as oligosaccharides cannot be cloned and are generally available in limited amounts.This overview recounts the background to the development of a microarray system that is poised for surveying proteomes for carbohydrate-binding activities and glycomes for assigning the oligosaccharide ligands.Particularly highlighted are sulfo-oligosaccharide and gluco-oligosaccharide recognition systems elucidated using microarrays.

View Article: PubMed Central - PubMed

Affiliation: The Glycosciences Laboratory, Department of Medicine, Imperial College London, London, United Kingdom. t.feizi@imperial.ac.uk

Show MeSH
Related in: MedlinePlus