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Journal of Virology, May 2005, p. 6472-6477, Vol. 79, No. 10
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.10.6472-6477.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Accumulation of Amino Acid Substitutions Promotes Irreversible Structural Changes in the Hemagglutinin of Human Influenza AH3 Virus during Evolution

Katsuhisa Nakajima,^1* Eri Nobusawa,¹ Alexander Nagy,² and Setsuko Nakajima¹

Department of Virology, Medical School, Nagoya City University, 1 Kawasumi, Mizuho-chou, Mizuho-ku, Nagoya 467-8601, Japan,¹ State Veterinary Institute, Sidlistni 24, 165 03 Prague, Czech Republic²

Received 25 October 2004/ Accepted 27 December 2004

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.

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* Corresponding author. Mailing address: Department of Virology, Medical School, Nagoya City University, 1 Kawasumi, Mizuho-chou, Mizuho-ku, Nagoya 467-8601, Japan. Phone: 81-52-853-8189. Fax: 81-52-853-3638. E-mail: nakajima{at}med.nagoya-cu.ac.jp.

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Journal of Virology, May 2005, p. 6472-6477, Vol. 79, No. 10
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.10.6472-6477.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

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