title: Molecular evolution of human influenza A viruses in a local area during eight influenza epidemics from 2000 to 2007.
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.
authors.affiliation: 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. hasanz@med.niigata-u.ac.jp
authors.forename: Hassan
authors.initials: H
authors.lastname: Zaraket
authors.forename: Reiko
authors.initials: R
authors.lastname: Saito
authors.forename: Isamu
authors.initials: I
authors.lastname: Sato
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Suzuki
authors.forename: Danjuan
authors.initials: D
authors.lastname: Li
authors.forename: Clyde
authors.initials: C
authors.lastname: Dapat
authors.forename: Isolde
authors.initials: I
authors.lastname: Caperig-Dapat
authors.forename: Taeko
authors.initials: T
authors.lastname: Oguma
authors.forename: Asami
authors.initials: A
authors.lastname: Sasaki
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Suzuki
mesh_terms: D000547:Amantadine / Q000494:pharmacology; D000998:Antiviral Agents / Q000494:pharmacology; D004196:Disease Outbreaks; D024882:Drug Resistance, Viral / Q000235:genetics; D019143:Evolution, Molecular; D014644:Genetic Variation; D006031:Glycosylation; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000235:genetics / Q000378:metabolism; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000145:classification / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D053122:Influenza A Virus, H3N2 Subtype / Q000145:classification / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D009980:Influenza A virus / Q000145:classification* / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D007251:Influenza, Human / Q000453:epidemiology* / Q000821:virology; D007564:Japan / Q000453:epidemiology; D008969:Molecular Sequence Data; D015394:Molecular Structure; D010802:Phylogeny; D021122:Protein Subunits / Q000737:chemistry / Q000235:genetics
chemical_list: D000998:Antiviral Agents; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D021122:Protein Subunits; C483468:hemagglutinin, human influenza A virus; D000547:Amantadine