title: Accumulation of amino acid substitutions promotes irreversible structural changes in the hemagglutinin of human influenza AH3 virus during evolution.
abstract: In order to clarify the effect of an accumulation of amino acid substitutions on the hemadsorption character of the influenza AH3 virus hemagglutinin (HA) protein, we introduced single-point amino acid changes into the HA1 domain of the HA proteins of influenza viruses isolated in 1968 (A/Aichi/2/68) and 1997 (A/Sydney/5/97) by using PCR-based random mutation or site-directed mutagenesis. These substitutions were classified as positive or negative according to their effects on the hemadsorption activity. The rate of positive substitutions was about 50% for both strains. Of 44 amino acid changes that were identical in the two strains with regard to both the substituted amino acids and their positions in the HA1 domain, 22% of the changes that were positive in A/Aichi/2/68 were negative in A/Sydney/5/97 and 27% of the changes that were negative in A/Aichi/2/68 were positive in A/Sydney/5/97. A similar discordance rate was also seen for the antigenic sites. These results suggest that the accumulation of amino acid substitutions in the HA protein during evolution promoted irreversible structural changes and therefore that antigenic changes in the H3HA protein may not be limited.
authors.affiliation: Department of Virology, Medical School, Nagoya City University, 1 Kawasumi, Mizuho-chou, Mizuho-ku, Nagoya 467-8601, Japan. nakajima@med.nagoya-cu.ac.jp
authors.forename: Katsuhisa
authors.initials: K
authors.lastname: Nakajima
authors.forename: Eri
authors.initials: E
authors.lastname: Nobusawa
authors.forename: Alexander
authors.initials: A
authors.lastname: Nagy
authors.forename: Setsuko
authors.initials: S
authors.lastname: Nakajima
mesh_terms: D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D000818:Animals; D000956:Antigens, Viral / Q000235:genetics* / Q000378:metabolism; D005075:Biological Evolution; D019556:COS Cells; D002522:Chlorocebus aethiops; D006382:Hemadsorption; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D009980:Influenza A virus / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D017354:Point Mutation; D017434:Protein Structure, Tertiary; D016415:Sequence Alignment
chemical_list: D000956:Antigens, Viral; D019267:Hemagglutinin Glycoproteins, Influenza Virus; C483468:hemagglutinin, human influenza A virus