title: The human H3N2 influenza viruses A/Victoria/3/75 and A/Hiroshima/52/2005 preferentially bind to α2-3-sialylated monosialogangliosides with fucosylated poly-N-acetyllactosaminyl chains.
abstract: Among influenza A viruses, subtype H3N2 is the major cause of human influenza morbidity and is associated with seasonal epidemics causing annually half million deaths worldwide. Influenza A virus infection is initiated via hemagglutinin that binds to terminally sialylated glycoconjugates exposed on the surface of target cells. Gangliosides from human granulocytes were probed using thin-layer chromatography overlay assays for their binding potential to H3N2 virus strains A/Victoria/3/75 and A/Hiroshima/52/2005. Highly polar gangliosides with poly-N-acetyllactosaminyl chains showing low chromatographic mobility exhibited strong virus adhesion which was entirely abolished by sialidase treatment. Auxiliary overlay assays using anti-sialyl Lewis(x) (sLe(x)) monoclonal antibodies showed identical binding patterns compared with those performed with the viruses. A comprehensive structural analysis of fractionated gangliosides by electrospray ionization quadrupole time-of-flight mass spectrometry revealed sLe(x) gangliosides with terminal Neu5Acα2-3Galβ1-4(Fucα1-3)GlcNAc epitope and extended neolacto (nLc)-series core structures as the preferential virus binding gangliosides. More precisely, sLe(x) gangliosides with nLc8, nLc10 and nLc12Cer cores, carrying sphingosine (d18:1) and a fatty acid with variable chain length (mostly C24:0, C24:1 or C16:0) in the ceramide moiety and one or two additional internal fucose residues in the oligosaccharide portion, were identified as the preferred receptors recognized by H3N2 virus strains A/Victoria/3/75 and A/Hiroshima/52/2005. This study describes glycan-binding requirements of hemagglutinin beyond binding to glycans with a specific sialic acid linkage of as yet undefined neutrophil receptors acting as ligands for H3N2 viruses. In addition, our results pose new questions on the biological and clinical relevance of this unexpected specificity of a subtype of influenza A viruses.
authors.affiliation: Institute for Hygiene, Biophysics, University of Münster, D-48149 Münster, Germany.
authors.forename: Iris
authors.initials: I
authors.lastname: Meisen
authors.forename: Tabea
authors.initials: T
authors.lastname: Dzudzek
authors.forename: Christina
authors.initials: C
authors.lastname: Ehrhardt
authors.forename: Stephan
authors.initials: S
authors.lastname: Ludwig
authors.forename: Michael
authors.initials: M
authors.lastname: Mormann
authors.forename: Regina
authors.initials: R
authors.lastname: Rosenbrück
authors.forename: Regine
authors.initials: R
authors.lastname: Lümen
authors.forename: Bernhard
authors.initials: B
authors.lastname: Kniep
authors.forename: Helge
authors.initials: H
authors.lastname: Karch
authors.forename: Johannes
authors.initials: J
authors.lastname: Müthing
mesh_terms: D002855:Chromatography, Thin Layer; D005643:Fucose / Q000378:metabolism*; D005732:Gangliosides / Q000378:metabolism*; D006098:Granulocytes / Q000378:metabolism*; D006801:Humans; D053122:Influenza A Virus, H3N2 Subtype / Q000145:classification / Q000378:metabolism*; D007251:Influenza, Human / Q000378:metabolism* / Q000821:virology; D009844:Oligosaccharides / Q000302:isolation & purification / Q000378:metabolism*; D011134:Polysaccharides / Q000378:metabolism*; D000080506:Sialyl Lewis X Antigen; D021241:Spectrometry, Mass, Electrospray Ionization; D053585:Virus Attachment
chemical_list: D005732:Gangliosides; D009844:Oligosaccharides; D011134:Polysaccharides; D000080506:Sialyl Lewis X Antigen; C025447:sialogangliosides; D005643:Fucose; C037199:poly-N-acetyllactosamine