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

Setsuko Nakajima, Katsuhisa Nakajima, Eri Nobusawa, Jin Zhao, Shigenori Tanaka, Kaori Fukuzawa

Research output: Contribution to journalArticlepeer-review

10 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)1179-1187
Number of pages9
JournalMICROBIOLOGY and IMMUNOLOGY
Volume51
Issue number12
DOIs
Publication statusPublished - 2007
Externally publishedYes

Keywords

  • Escape mutant
  • Hemagglutinin
  • Influenza virus
  • Protein modeling

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Virology

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