Association analyses of large-scale glycan microarray data reveal novel host-specific substructures in influenza A virus binding glycans.

Nan Zhao,Xiu-Feng Wan,Brigitte E Martin,Feng Luo,Chun-Kai Yang

doi:10.1038/srep15778

Nan Zhao, Xiu-Feng Wan + Show 3 more

Open Access

https://doi.org/10.1038/srep15778

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Abstract

Influenza A viruses can infect a wide variety of animal species and, occasionally, humans. Infection occurs through the binding formed by viral surface glycoprotein hemagglutinin and certain types of glycan receptors on host cell membranes. Studies have shown that the α2,3-linked sialic acid motif (SA2,3Gal) in avian, equine, and canine species; the α2,6-linked sialic acid motif (SA2,6Gal) in humans; and SA2,3Gal and SA2,6Gal in swine are responsible for the corresponding host tropisms. However, more detailed and refined substructures that determine host tropisms are still not clear. Thus, in this study, we applied association mining on a set of glycan microarray data for 211 influenza viruses from five host groups: humans, swine, canine, migratory waterfowl, and terrestrial birds. The results suggest that besides Neu5Acα2–6Galβ, human-origin viruses could bind glycans with Neu5Acα2–8Neu5Acα2–8Neu5Ac and Neu5Gcα2–6Galβ1–4GlcNAc substructures; Galβ and GlcNAcβ terminal substructures, without sialic acid branches, were associated with the binding of human-, swine-, and avian-origin viruses; sulfated Neu5Acα2–3 substructures were associated with the binding of human- and swine-origin viruses. Finally, through three-dimensional structure characterization, we revealed that the role of glycan chain shapes is more important than that of torsion angles or of overall structural similarities in virus host tropisms.

Highlights

In this study, we applied association mining on a set of glycan microarray data for 211 influenza viruses from five host groups: humans, swine, canine, migratory waterfowl, and terrestrial birds
The results suggest that besides Neu5Acα2–6Galβ, human-origin viruses could bind glycans with Neu5Acα2–8Neu5Acα2–8Neu5Ac and Neu5Gcα2–6Galβ1–4GlcNAc substructures; Galβ and GlcNAcβ terminal substructures, without sialic acid branches, were associated with the binding of human, swine, and avian-origin viruses; sulfated Neu5Acα[2,3] substructures were associated with the binding of human- and swine-origin viruses
Influenza virus–specific features derived from glycan microarray data by partial least squares (PLS) regression and feature selection

Summary

Introduction

In this study, we applied association mining on a set of glycan microarray data for 211 influenza viruses from five host groups: humans, swine, canine, migratory waterfowl, and terrestrial birds. The carbohydrates or glycans in host cells serve as the receptors for influenza viruses and are key to successful virus entry, the first step in influenza infection[5]. The structures of these glycan receptors have been shown to be unique in animal hosts and even within different tissues in the same host, and these unique glycan structures determine host and tissue tropisms of influenza A viruses. By presenting multiple glycans or glycoconjugates printed on a single slide, the glycan microarray technique has offered high-throughput analyses of the glycan-binding profile of influenza viruses[15,16]

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