Journal
SCIENTIFIC REPORTS
Volume 8, Issue -, Pages -Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/s41598-018-34175-3
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Funding
- Austrian Science Fund (FWF) [J3342-B21]
- Australian Research Council (ARC) [DP110104028, FT120100419]
- National Health and Medical Research Council (NHMRC) [1071659, 1006618]
- Area of Excellence Scheme of the University Grants Committee by Government of Hong Kong Special Administrative Region [AoE/M-12/96]
- Australian Research Council [FT120100419] Funding Source: Australian Research Council
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The initial stage of host cell infection by influenza A viruses (IAV) is mediated through interaction of the viral haemagglutinin (HA) with cell surface glycans. The binding requirement of IAVs for Gal beta(1,4) Glc/GlcNAc (lactose/lactosamine) glycans with a terminal alpha(2,6)-linked (human receptors) or alpha(2,3)linked (avian receptors) N-acetylneuraminic residue commonly found on N-glycans, is well-established. However the role and significance of sialylated Gal beta(1,3) GalNAc (core 1) epitopes that are typical O-glycoforms in influenza virus pathogenesis remains poorly detailed. Here we report a multidisciplinary study using NMR spectroscopy, virus neutralization assays and molecular modelling, into the potential for IAV to engage sialyl-Gal beta(1,3) GalNAc O-glycoforms for cell attachment. H5 containing virus like particles (VLPs) derived from an H5N1 avian IAV strain show a significant involvement of the O-glycan-specific GalNAc residue, coordinated by a EQTKLY motif conserved in highly pathogenic avian influenza (HPAI) strains. Notably, human pandemic H1N1 influenza viruses shift the preference from 'huma-nlike' a(2,6)-linkages in sialylated Gal beta(1,4) Glc/GlcNAc fragments to 'avian-like' alpha(2,3)-linkages in sialylated Gal beta(1,3) GalNAc without involvement of the GalNAc residue. Overall, our study suggests that sialylated Gal beta(1,3) GalNAc as O-glycan core 1 glycoforms are involved in the influenza A virus life cycle and play a particularly crucial role during infection of HPAI strains.
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