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Journal of Virology, September 2003, p. 10088-10098, Vol. 77, No. 18
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.18.10088-10098.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Restriction of Amino Acid Change in Influenza A Virus H3HA: Comparison of Amino Acid Changes Observed in Nature and In Vitro

Katsuhisa Nakajima,1* Eri Nobusawa,1 Ken Tonegawa,2 and Setsuko Nakajima1

Department of Virology,1 Department of Internal Medicine and Bioregulation, Nagoya City University, 1 Kawasumi, Mizuho-chou, Mizuho-ku, Nagoya 467-8601, Japan2

Received 3 April 2003/ Accepted 19 June 2003

We introduced 248 single-point amino acid changes into hemagglutinin (HA) protein of the A/Aichi/2/68 (H3N2) strain by a PCR random mutation method. These changes were classified as positive or negative according to their effect on hemadsorption activity. We observed following results. (i) The percentage of surviving amino acid changes on the HA1 domain that did not abrogate hemadsorption activity was calculated to be ca. 44%. In nature, it is estimated to be ca. 39.6%. This difference in surviving amino acid changes on the HA protein between natural isolates and in vitro mutants might be due to the immune pressure against the former. (ii) A total of 26 amino acid changes in the in vitro mutants matched those at which mainstream amino acid changes had occurred in the H3HA1 polypeptide from 1968 to 2000. Of these, 25 were positive. We suggest that the majority of amino acid changes on the HA protein during evolution might be restricted to those that were positive on the HA of A/Aichi/2/68. (iii) We constructed two-point amino acid changes on the HA protein by using positive mutants. These two-point amino acid changes with a random combination did not inhibit hemadsorption activity. It is possible that an accumulation of amino acid change might occur without order. (iv) From the analysis of amino acids participating in mainstream amino acid change, each antigenic site could be further divided into smaller sites. The amino acid substitutions in the gaps between these smaller sites resulted in mostly hemadsorption-negative changes. These gap positions may play an important role in maintaining the function of the HA protein, and therefore amino acid changes are restricted at these locations.

* Corresponding author. Mailing address: Department of Virology, 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.

Journal of Virology, September 2003, p. 10088-10098, Vol. 77, No. 18
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.18.10088-10098.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Jian, J.-W., Chen, G.-W., Lai, C.-T., Hsu, L.-C., Chen, P.-J., Kuo, S. H.-S., Wu, H.-S., Shih, S.-R. (2008). Genetic and Epidemiological Analysis of Influenza Virus Epidemics in Taiwan during 2003 to 2006. J. Clin. Microbiol. 46: 1426-1434 [Abstract] [Full Text]  
  • Nakajima, K., Nobusawa, E., Nagy, A., Nakajima, S. (2005). Accumulation of Amino Acid Substitutions Promotes Irreversible Structural Changes in the Hemagglutinin of Human Influenza AH3 Virus during Evolution. J. Virol. 79: 6472-6477 [Abstract] [Full Text]  
  • Abe, Y., Takashita, E., Sugawara, K., Matsuzaki, Y., Muraki, Y., Hongo, S. (2004). Effect of the Addition of Oligosaccharides on the Biological Activities and Antigenicity of Influenza A/H3N2 Virus Hemagglutinin. J. Virol. 78: 9605-9611 [Abstract] [Full Text]  


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