Comparison of epitope structures of H3HAs through protein modeling of influenza A virus hemagglutinin: mechanism for selection of antigenic variants in the presence of a monoclonal antibody.
Starting with nine plaques of influenza A/Kamata/14/91(H3N2) virus, we selected mutants in the presence of monoclonal antibody 203 (mAb203). In total, amino acid substitutions were found at nine positions (77, 80, 131, 135, 141, 142, 143, 144 and 146), which localized in the antigenic site A of the hemagglutinin (HA). The escape mutants differed in the extent to which they had lost binding to mAb203. HA protein with substitutions of some amino acid residues created by site-directed mutagenesis in the escape mutants retained the ability to bind to mAb203. Changes in the amino acid character affecting charge or hydrophobicity accounted for the binding capacity to the antibody of the HA with most of the substitutions in the escape mutants and binding-positive mutants. However, the effect of some amino acid substitutions remained unexplained. A three-dimensional model of the 1991 HA was constructed and used to analyze substituted amino acids in these mutants for the accessible surface hydrophobic and hydrophilic characters. One amino acid substitution in an escape mutant and another amino acid substitution in a binding-positive mutant seemed to be explained by the changes noted on this model.
Nakajima
Setsuko
S
Department of Virology, Medical School, Nagoya City University, Mizuho-ku, Aichi, Japan. setsuko@med.nagoya-cu.ac.jp
Nakajima
Katsuhisa
K
Nobusawa
Eri
E
Zhao
Jin
J
Tanaka
Shigenori
S
Fukuzawa
Kaori
K
D019943:Amino Acid Substitution / Q000235:genetics* / Q000276:immunology*; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000378:metabolism; D000914:Antibodies, Viral / Q000276:immunology / Q000378:metabolism; D000940:Antigenic Variation / Q000235:genetics / Q000276:immunology*; D000939:Epitopes / Q000235:genetics / Q000276:immunology*; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000235:genetics / Q000276:immunology*; D057927:Hydrophobic and Hydrophilic Interactions; D053122:Influenza A Virus, H3N2 Subtype / Q000235:genetics / Q000276:immunology*; D008958:Models, Molecular; D016297:Mutagenesis, Site-Directed; D011485:Protein Binding
D000911:Antibodies, Monoclonal; D000914:Antibodies, Viral; D000939:Epitopes; D019267:Hemagglutinin Glycoproteins, Influenza Virus; C483468:hemagglutinin, human influenza A virus