Monoclonal antibodies differentially affect the interaction between the hemagglutinin of H9 influenza virus escape mutants and sialic receptors.
To determine the receptor binding properties of various H9 influenza virus escape mutants in the presence and absence of antibody, sialyloligosaccharides conjugated with biotinylated polyacrylamide were used. A mutant virus with a L226Q substitution showed an increased affinity for the Neu5Acalpha2-3Galbeta1-4Glc. Several escape mutants viruses carrying the mutation N193D bound to Neu5Acalpha2-6Galbeta1-4GlcNAc considerably stronger than to Neu5Acalpha2-6Galbeta1-4Glc. Several monoclonal antibodies unable to neutralize the escape mutants preserved the ability to bind to the hemagglutinin as revealed by enzyme-linked immunosorbent assay. In each case, the bound monoclonal antibodies did not prevent the binding of the mutant HA to high affinity substrates and did not displace them from the virus binding sites. Together, these data suggest that amino acid changes selected by antibody pressure may be involved in the specificity of host-cell recognition by H9 hemagglutinin and in the ability of viruses with these mutations to escape the neutralizing effect of antibodies in a differential way, depending on the specificity of the host cell receptor. It may be important in the natural evolution of the H9 subtype, a plausible candidate for the agent likely to cause a future pandemic.
Laboratory of Virus Physiology, The D.I. Ivanovsky Institute of Virology, 16 Gamaleya Street, Moscow 123098, Russia. Ilyushina_NA@inbox.ru
Natalia
N
Ilyushina
Irina
I
Rudneva
Alexandra
A
Gambaryan
Nicolai
N
Bovin
Nikolai
N
Kaverin
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology*; D000940:Antigenic Variation; D001665:Binding Sites; D001667:Binding, Competitive; D006385:Hemagglutination Inhibition Tests; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000737:chemistry / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D009980:Influenza A virus / Q000145:classification / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009154:Mutation; D009844:Oligosaccharides / Q000378:metabolism*; D011991:Receptors, Virus / Q000378:metabolism*; D017422:Sequence Analysis, DNA
D000911:Antibodies, Monoclonal; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D009844:Oligosaccharides; D011991:Receptors, Virus; C016735:sialooligosaccharides