title: Emergence and phylogenetic analysis of amantadine-resistant influenza a subtype H3N2 viruses in Dublin, Ireland, over Six Seasons from 2003/2004 to 2008/2009.
abstract: OBJECTIVE
  To determine the prevalence of amantadine-resistant influenza A viruses and perform genetic analysis of isolates collected in Dublin during six seasons (2003/2004 to 2008/2009).
  
  
  METHODS
  Known mutations in the matrix 2 gene (M2) conferring amantadine resistance were screened and phylogenetic analysis of the haemagglutinin gene (HA) performed.
  
  
  RESULTS
  Of 1,180 samples, 67 influenza A viruses were isolated, 88% of which were subtype H3N2. Amantadine resistance was only found in subtype H3N2 and increased dramatically from 7% in 2003/2004 to 90% in 2008/2009. A maximum likelihood tree of the HA gene of influenza A H3N2 isolates differentiated them into two distinct clades, clade N and clade S, where the majority of isolates were amantadine-resistant and amantadine-sensitive, respectively. The clades were distinguished by amino acid substitutions, S193F and D225N, which probably conferred a selective advantage for the spread of such viruses. Phylogenetic analysis showed some degree of antigenic drift when compared with the vaccine strain of the corresponding season.
  
  
  CONCLUSIONS
  This study showed that circulation in Ireland of a distinct lineage, clade N, among H3N2 viruses favoured emergence of amantadine resistance. Furthermore, comparison of circulating Irish viruses and vaccine strains used in the northern hemisphere showed high similarity.
authors.affiliation: Department of Clinical Microbiology, Trinity College Dublin, Ireland.
authors.forename: A
authors.initials: A
authors.lastname: Salter
authors.forename: B
authors.initials: B
authors.lastname: Ni Laoi
authors.forename: B
authors.initials: B
authors.lastname: Crowley
mesh_terms: D000547:Amantadine / Q000494:pharmacology / Q000627:therapeutic use*; D000595:Amino Acid Sequence; D000998:Antiviral Agents / Q000494:pharmacology / Q000627:therapeutic use*; D004252:DNA Mutational Analysis; D024882:Drug Resistance, Viral; D040961:Genetic Drift; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000235:genetics; D006801:Humans; D053122:Influenza A Virus, H3N2 Subtype / Q000187:drug effects / Q000235:genetics*; D007251:Influenza, Human / Q000188:drug therapy* / Q000453:epidemiology; D007494:Ireland / Q000453:epidemiology; D016013:Likelihood Functions; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D010802:Phylogeny; D014763:Viral Matrix Proteins / Q000235:genetics; D000086082:Viroporin Proteins
chemical_list: D000547:Amantadine; D000998:Antiviral Agents; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D014763:Viral Matrix Proteins; C488937:M2 protein, Influenza A virus; D000086082:Viroporin Proteins