Association analyses of large-scale glycan microarray data reveal novel host-specific substructures in influenza A virus binding glycans.
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.
Department of Basic Sciences, College of Veterinary Medicine, Mississippi State University, MS, USA.|Institute for Genomics, Biocomputing &Biotechnology, Mississippi State University, MS, USA.
Nan
N
Zhao
Department of Basic Sciences, College of Veterinary Medicine, Mississippi State University, MS, USA.
Brigitte E
BE
Martin
Department of Basic Sciences, College of Veterinary Medicine, Mississippi State University, MS, USA.
Chun-Kai
CK
Yang
School of Computing, Clemson University, Clemson, SC, USA.
Feng
F
Luo
Department of Basic Sciences, College of Veterinary Medicine, Mississippi State University, MS, USA.|Institute for Genomics, Biocomputing &Biotechnology, Mississippi State University, MS, USA.
Xiu-Feng
XF
Wan
D000595:Amino Acid Sequence / Q000502:physiology; D000818:Animals; D001717:Birds / Q000821:virology; D004285:Dogs; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000378:metabolism; D006801:Humans; D009980:Influenza A virus / Q000378:metabolism*; D046228:Microarray Analysis / Q000379:methods; D019158:N-Acetylneuraminic Acid / Q000378:metabolism; D011134:Polysaccharides / Q000378:metabolism*; D011991:Receptors, Virus / Q000378:metabolism; D013552:Swine
D019267:Hemagglutinin Glycoproteins, Influenza Virus; D011134:Polysaccharides; D011991:Receptors, Virus; D019158:N-Acetylneuraminic Acid