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Molecular evolution of human influenza A viruses in a local area during eight influenza epidemics from 2000 to 2007

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Abstract

A total of 1,041 human influenza A virus isolates were collected at a clinic in Niigata, Japan, during eight influenza seasons from 2000 to 2007. The H3N2 subtype accounted for 75.4% of the isolates, and the rest were H1N1. Extremely high rates of amantadine-resistant strains of H3N2 subtype were observed in 2005/2006 (100%) and 2006/2007 (79.4%), while amantadine-resistant strains of H1N1 subtype were only detected in 2006/2007 (48.2%). Sequence and phylogenetic analysis of the HA1 subunit of the hemagglutinin (HA) gene revealed a characteristic linear trunk in the case of H3N2 viruses and a multi-furcated tree in the case of H1N1 and showed a higher sequence diversity among H3N2 strains than H1N1 strains. Mutations in the HA1 from both subtypes were mainly found in the globular region, and only one-third of these were retained for two or more successive years. Higher diversity of H3N2 viruses was mainly attributable to a higher fixation rate of non-synonymous mutations and to a lesser extent to a higher nucleotide substitution rate than for H1N1. Our analysis showed evidence of four positively selected sites in the HA1 of H1 and five sites in that of H3, four of which were novel. Finally, acquisition or loss of N-glycosylation sites was shown to contribute to the evolution of influenza A virus, especially in the case of H3N2, which had a higher tendency to acquire new glycosylation sites.

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Acknowledgments

This study was supported by Japan Grants-in-Aid for Scientific Research, from Monbu Kagakusho (Ministry of Education, Culture, Sports, Science and Technology, Japan), and Acute Respiratory Infections Panels, United States-Japan Cooperative Medical Science Program (US Department of Health and Human Services, US Department of State, United States, Ministry of Foreign Affairs, Ministry of Health, Labor, and Welfare, and Ministry of Education, Culture, Sports, Science and Technology, Japan). We are grateful to Dr. Akinori Miyashita and Dr. Ryozo Kuwano in the Department of Molecular Genetics, Bioresource Science Branch, Center for Bioresources, Brain Research Institute, Niigata University, for use of the DNA sequencer. We thank Ms. Akemi Watanabe for technical assistance for virus isolation, and Ms. Yoshiko Kato for intensive secretarial work.

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Authors and Affiliations

  1. Division of Public Health, Department of Infectious Disease Control and International Medicine, Graduate School of Medical and Dental Sciences, Niigata University, 1-757, Asahimachi-Dori, Niigata, Niigata, 951-8510, Japan

    Hassan Zaraket, Reiko Saito, Yasushi Suzuki, Danjuan Li, Clyde Dapat, Isolde Caperig-Dapat, Taeko Oguma, Asami Sasaki & Hiroshi Suzuki

  2. Yoiko Pediatric Clinic, Niigata, Niigata, Japan

    Isamu Sato

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  1. Hassan Zaraket
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Correspondence to Hassan Zaraket.

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Zaraket, H., Saito, R., Sato, I. et al. Molecular evolution of human influenza A viruses in a local area during eight influenza epidemics from 2000 to 2007. Arch Virol 154, 285–295 (2009). https://doi.org/10.1007/s00705-009-0309-9

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  • DOI: https://doi.org/10.1007/s00705-009-0309-9

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