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Potent neutralization of human H3N2 viruses by GNL lectin targeting conserved oligomannose N-linked glycans

ABSTRACT: Hemagglutinins (HAs) from human influenza viruses adapt to specifically bind alpha 2-6-linked sialosides, overcoming a receptor-defined species barrier that is distinct from the alpha 2-3 specificity of avian virus progenitors. Additionally, human-adapted HAs incrementally gain glycosylation sites over time, although the nature and biological consequences of the additional glycans remain poorly defined. Using quantitative glycomic analysis, we show that HAs from human pandemic viruses exhibit significant proportions of high-mannose type N-linked glycans throughout the head domain, whereas poorly adapted avian-origin HAs have predominately complex-type glycans. Even at low frequencies, oligomannose sites present in all tested recombinant HAs and whole-viruses can be specifically labelled for universal detection. Using molecular modelling, we find that the positions of high-mannose glycosites on the HA of human H1N1 and H3N2 strains are conserved. Inhibition studies show that high-mannose-binding lectins possess broad capacity to inhibit contemporary H3N2 strains and highlight potential for therapeutic development.

INSTRUMENT(S): Orbitrap Fusion, LTQ Orbitrap Elite

ORGANISM(S): Homo Sapiens (ncbitaxon:9606)

SUBMITTER: James C. Paulson

PROVIDER: MSV000084953 | MassIVE | Wed Feb 12 13:12:00 GMT 2020

REPOSITORIES: MassIVE

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