Human influenza A virus hemagglutinin distinguishes sialyloligosaccharides in membrane-associated gangliosides as its receptor which mediates the adsorption and fusion processes of virus infection. Specificity for oligosaccharides and sialic acids and the sequence to which sialic acid is attached.
Human influenza A virus isolates bearing antigenically different H1 (A/PR/8/34), H2 (A/Japan/305/57), and H3 (A/Aichi/2/68, A/X-31) hemagglutinin serotypes caused extensive hemagglutination, low pH fusion, and hemolysis of asialoerythrocytes reconstituted with gangliosides. Sialylparaglobosides (IV3NeuAc-nLc4Cer, IV6NeuAc-nLc4Cer), I-active and i-active (VI3NeuAc-nLc6Cer) gangliosides, and GM3-NeuAc commonly exhibited significant specific receptor activity toward the viruses. A/PR/8/34 recognized IV3NeuAc-nLc4Cer containing the NeuAc alpha 2-3Gal sequence preferentially over IV6NeuAc-nLc4Cer containing NeuAc alpha 2-6Gal, whereas the other two recognized the NeuAc alpha 2-6Gal sequence preferentially over NeuAc alpha 2-3Gal. Responsiveness of erythrocytes labeled with gangliosides containing NeuGc to the viruses used was considerably lower than that of erythrocytes labeled with gangliosides containing NeuAc. The activities of GM1a, GM2, and GD1b bearing NeuAc on inner galactose of the ganglio series core were also very low. These results indicate that sialyloligosaccharides of IV3NeuAc-nLc4Cer, IV6NeuAc-nLc4Cer, I-active ganglioside, and VI3NeuAc-nLc6Cer in addition to GM3-NeuAc and GM1b-NeuAc (Suzuki, Y., Matsunaga, M., and Matsumoto, M. (1985), J. Biol. Chem. 260, 1362-1365; Suzuki, Y., Matsunaga, M., Nagao, Y., Taki, T., Hirabayashi, Y., and Matsumoto, M. (1985) Vaccine 3, 201-203) are functional receptor determinants toward hemagglutinin of human influenza A viruses, and the viruses differentiate microdomains of the gangliosides, such as the sialic acid species (NeuAc, NeuGc) and the sequence of sialic acid linkages (NeuAc alpha 2-3Gal, NeuAc alpha 2-6Gal).
D000818:Animals; D002236:Carbohydrate Conformation; D002240:Carbohydrate Sequence; D002645:Chickens; D004912:Erythrocytes / Q000276:immunology; D005732:Gangliosides / Q000032:analysis* / Q000378:metabolism; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D006389:Hemagglutinins, Viral; D006801:Humans; D009980:Influenza A virus / Q000276:immunology* / Q000502:physiology; D009844:Oligosaccharides / Q000032:analysis*; D011956:Receptors, Cell Surface; D011971:Receptors, Immunologic; D011991:Receptors, Virus; D012703:Serotyping; D012794:Sialic Acids / Q000032:analysis
D005732:Gangliosides; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D006389:Hemagglutinins, Viral; D009844:Oligosaccharides; D011956:Receptors, Cell Surface; D011971:Receptors, Immunologic; D011991:Receptors, Virus; D012794:Sialic Acids; C016735:sialooligosaccharides; C028583:sialyloligosaccharide receptor