Unraveling the role of the secretor antigen in human rotavirus attachment to histo-blood group antigens

• DOI: 10.1371/journal.ppat.1007865
• Publication Date: 2019-06-21T17:34:52Z
• Authors: Roberto Gozalbo-R...; J. Rafael Ciges-T...; Susana Vila-Vicent; Javier Buesa; Cristina Santiso-...; Vicente Monedero; María J. Yebra; Alberto Marina; Jesús Rodríguez-Díaz
• Keywords: Fucosylation; Binding selectivity

Rotavirus is the leading agent causing acute gastroenteritis in young children, with P[8] genotype accounting for more than 80% of infections humans. The molecular bases binding VP8* domain from VP4 spike protein to its cellular receptor, secretory H type-1 antigen (Fuc-α1,2-Gal-β1,3-GlcNAc; H1), and precursor lacto-N-biose (Gal-β1,3-GlcNAc; LNB) have been determined. resolution crystal structures complex H1 LNB site-directed mutagenesis experiments revealed that both glycans bind through a pocket shared other members P[II] genogroup (i.e.: P[4], P[6] P[19]). Our results show L-fucose moiety only displays indirect contacts VP8*. However, induced conformational changes increase ligand affinity by two-fold, as measured surface plasmon resonance (SPR), providing explanation different susceptibility rotavirus infection between secretor non-secretor individuals. unexpected interaction LNB, building block human milk oligosaccharides, resulted inhibition infection, highlighting role possible application this disaccharide an antiviral. While key amino acids H1/LNB were highly conserved genogroup, differences found affinities among distinct genetic lineages. variation explained subtle structural acid vicinity pocket, fine-tuning mechanism glycan rotavirus.