Single-amino-acid substitution in an antigenic site of influenza virus hemagglutinin can alter the specificity of binding to cell membrane-associated gangliosides.
Antigenic variants of influenza virus A/Mem/1/71-Bel/42 (H3N1) selected with monoclonal antibodies and having single substitutions in their hemagglutinins were examined for their ability to hemagglutinate and hemolyse erythrocytes coated with different gangliosides. The majority of variants, including one with a substitution near the receptor-binding site (Asn-133----Lys), did not differ from the parent in specificity for receptor molecules. However, a substitution in HA1 at residue 205 (Ser----Tyr), which is distant from the receptor-binding site in antigenic site D, affected hemagglutination and hemolysis of erythrocytes coated with sialyl-paraglobosides. The variant preferentially recognized N-acetylneuraminic acid-alpha 2,6-galactose linkages to sialylparaglobosides, whereas the parent and other variants preferentially recognized N-acetylneuraminic acid-alpha 2,3-galactose linkages. In the trimeric hemagglutinin molecule, residue 205 is located across the subunit interface from the receptor-binding site. The bulky hydrophobic tyrosine in the variant may cause a conformational change in the receptor-binding pocket on the neighboring subunit and influence receptor binding.
Suzuki
Y
Y
Department of Biochemistry, University of Shizuoka School of Pharmaceutical Science, Japan.
Kato
H
H
Naeve
C W
CW
Webster
R G
RG
D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D000939:Epitopes; D005732:Gangliosides / Q000378:metabolism*; D006384:Hemagglutination; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D006389:Hemagglutinins, Viral / Q000032:analysis / Q000276:immunology* / Q000378:metabolism; D006461:Hemolysis; D009980:Influenza A virus / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D019158:N-Acetylneuraminic Acid; D012794:Sialic Acids / Q000378:metabolism
D000939:Epitopes; D005732:Gangliosides; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D006389:Hemagglutinins, Viral; D012794:Sialic Acids; D019158:N-Acetylneuraminic Acid