Avian influenza A viruses differ from human viruses by recognition of sialyloligosaccharides and gangliosides and by a higher conservation of the HA receptor-binding site.

Avian influenza virus strains representing most hemagglutinin (HA) subtypes were compared with human influenza A (H1N1,H3N2) and B virus isolates, including those with no history of passaging in embryonated hen's eggs, for their ability to bind free N-acetylneuraminic acid (Neu5Ac) and sialylollgosaccharides in a competitive binding assay and to attach to gangliosides in a solid-phase adsorption assay. The avian viruses, irrespective of their HA subtype, showed a higher affinity for sialyl-3-lactose and the other Neu5Ac2-3Gal-terminated oligosaccharides and a lower affinity for sialyl-6-lactose than for free Neu5Ac, indicative of specific interactions between the HA and the 3-linked Gal and poor accommodation of 6-linked Gal in the avian receptor-binding site (RBS). Human H1 and H3 strains, by contrast, were unable to bind to 3-linked Gal, interacting instead with the asialic portion of sialyl-6-(N-acetyllactosamine). Different parts of this moiety were recognized by H3 and H1 subtype viruses (Gal and GlcNAc, respectively). Comparison of the HA amino acid sequences revealed that residues in positions. 138, 190, 194, 225, 226, and 228 are conserved in the avian RBS, while the human HAs harbor substitutions at these positions. A characteristic feature of avian viruses was their binding to Neu5Ac2-3Gal-containing gangliosides. This property of avian precursor viruses was preserved in early human H3 isolates, but was gradually lost with further circulation of the H3 HA in humans. Consequently, later human H3 isolates, as well as H1 and type B human strains, were unable to bind to short Neu5Ac2-3Gal-terminated gangliosides, an incompatibility that correlated with higher glycosylation of the HA globular head of human viruses. Our results suggest that the RBS is highly conserved among HA subtypes of avian influenza virus, while that of human viruses displays distinctive genotypic and phenotypic variability.

[1]  I. Schulze,et al.  Single amino acid substitutions in the hemagglutinin can alter the host range and receptor binding properties of H1 strains of influenza A virus , 1991, Journal of virology.

[2]  R. Webster,et al.  Influenza—an emerging and re-emerging disease , 1994 .

[3]  S. Hakomori.  Chemistry of Glycosphingolipids , 1983 .

[4]  G. N. Rogers,et al.  Receptor binding properties of human and animal H1 influenza virus isolates. , 1989, Virology.

[5]  S. Teneberg,et al.  Influenza viruses display high-affinity binding to human polyglycosylceramides represented on a solid-phase assay surface. , 1996, Virology.

[6]  W. Garten,et al.  A H1 hemagglutinin of a human influenza A virus with a carbohydrate-modulated receptor binding site and an unusual cleavage site , 1993, Virus Research.

[7]  H. Klenk,et al.  Sialic Acid as Receptor Determinant of Ortho- and Paramyxoviruses , 1995 .

[8]  M. Iwamori,et al.  Ganglioside composition of rabbit thymus. , 1981, Biochimica et Biophysica Acta.

[9]  M. Matrosovich,et al.  A solid-phase enzyme-linked assay for influenza virus receptor-binding activity. , 1992, Journal of virological methods.

[10]  J. Robertson.  Clinical influenza virus and the embryonated Hen's egg , 1993 .

[11]  Y. Suzuki,et al.  Gangliosides as influenza virus receptors. Variation of influenza viruses and their recognition of the receptor sialo-sugar chains. , 1994, Progress in lipid research.

[12]  W. J. Bean,et al.  Evolution of the H3 influenza virus hemagglutinin from human and nonhuman hosts , 1992, Journal of virology.

[13]  R. Webster,et al.  Receptor specificity in human, avian, and equine H2 and H3 influenza virus isolates. , 1994, Virology.

[14]  J. Paulson,et al.  Recognition of monovalent sialosides by influenza virus H3 hemagglutinin. , 1987, Virology.

[15]  K. Karlsson.  Preparation of total nonacid glycolipids for overlay analysis of receptors for bacteria and viruses and for other studies. , 1987, Methods in enzymology.

[16]  S. Teneberg,et al.  Receptor‐active glycolipids of epithelial cells of the small intestine of young and adult pigs in relation to susceptibility to infection with Escherichia coli K99 , 1990, FEBS letters.

[17]  N. Bovin,et al.  Human influenza virus recognition of sialyloligosaccharides , 1995, FEBS letters.

[18]  J. Skehel,et al.  The structure and function of the hemagglutinin membrane glycoprotein of influenza virus. , 1987, Annual review of biochemistry.

[19]  A. Rosenberg.  Biology of the Sialic Acids , 1995, Springer US.

[20]  N. Cox,et al.  Genetic and antigenic analyses of influenza A (H1N1) viruses, 1986-1991. , 1993, Virus research.

[21]  R. Webster,et al.  Influence of host cell-mediated variation on the international surveillance of influenza A (H3N2) viruses. , 1993, Virology.

[22]  R. Yu,et al.  Methods for Isolation and Analysis of Gangliosides , 1978 .

[23]  S. Cusack,et al.  Structure of the influenza virus haemagglutinin complexed with its receptor, sialic acid , 1988, Nature.

[24]  K. Karlsson.  Animal glycosphingolipids as membrane attachment sites for bacteria. , 1989, Annual review of biochemistry.

[25]  N. Cox,et al.  The antigenicity and evolution of influenza H1 haemagglutinin, from 1950-1957 and 1977-1983: two pathways from one gene. , 1986, Virology.

[26]  A. Golbraikh,et al.  Probing of the receptor-binding sites of the H1 and H3 influenza A and influenza B virus hemagglutinins by synthetic and natural sialosides. , 1993, Virology.

[27]  J. Skehel,et al.  Binding of influenza virus hemagglutinin to analogs of its cell-surface receptor, sialic acid: analysis by proton nuclear magnetic resonance spectroscopy and X-ray crystallography. , 1994, Biochemistry.

[28]  C. Naeve,et al.  Egg fluids and cells of the chorioallantoic membrane of embryonated chicken eggs can select different variants of influenza A (H3N2) viruses. , 1995, Virology.

[29]  V. Hinshaw,et al.  The hemagglutinins of duck and human H1 influenza viruses differ in sequence conservation and in glycosylation , 1993, Journal of virology.

[30]  W. J. Bean,et al.  Origin of the pandemic 1957 H2 influenza A virus and the persistence of its possible progenitors in the avian reservoir. , 1993, Virology.

[31]  C. Naeve,et al.  Mutations in the hemagglutinin receptor-binding site can change the biological properties of an influenza virus , 1984, Journal of virology.

[32]  J. Paulson.  Interactions of Animal Viruses with Cell Surface Receptors , 1985 .

[33]  Y Tateno,et al.  Comparison of complete amino acid sequences and receptor-binding properties among 13 serotypes of hemagglutinins of influenza A viruses. , 1991, Virology.