title: Mutation analysis of 2009 pandemic influenza A(H1N1) viruses collected in Japan during the peak phase of the pandemic.
abstract: BACKGROUND
  Pandemic influenza A(H1N1) virus infection quickly circulated worldwide in 2009. In Japan, the first case was reported in May 2009, one month after its outbreak in Mexico. Thereafter, A(H1N1) infection spread widely throughout the country. It is of great importance to profile and understand the situation regarding viral mutations and their circulation in Japan to accumulate a knowledge base and to prepare clinical response platforms before a second pandemic (pdm) wave emerges.
  
  
  METHODS
  A total of 253 swab samples were collected from patients with influenza-like illness in the Osaka, Tokyo, and Chiba areas both in May 2009 and between October 2009 and January 2010. We analyzed partial sequences of the hemagglutinin (HA) and neuraminidase (NA) genes of the 2009 pdm influenza virus in the collected clinical samples. By phylogenetic analysis, we identified major variants of the 2009 pdm influenza virus and critical mutations associated with severe cases, including drug-resistance mutations.
  
  
  CONCLUSIONS
  Our sequence analysis has revealed that both HA-S220T and NA-N248D are major non-synonymous mutations that clearly discriminate the 2009 pdm influenza viruses identified in the very early phase (May 2009) from those found in the peak phase (October 2009 to January 2010) in Japan. By phylogenetic analysis, we found 14 micro-clades within the viruses collected during the peak phase. Among them, 12 were new micro-clades, while two were previously reported. Oseltamivir resistance-related mutations, i.e., NA-H275Y and NA-N295S, were also detected in sporadic cases in Osaka and Tokyo.
authors.affiliation: Omics Science Center, RIKEN Yokohama Institute, Yokohama, Japan.
authors.forename: Jean-Étienne
authors.initials: JÉ
authors.lastname: Morlighem
authors.forename: Shintaro
authors.initials: S
authors.lastname: Aoki
authors.forename: Mami
authors.initials: M
authors.lastname: Kishima
authors.forename: Mitsue
authors.initials: M
authors.lastname: Hanami
authors.forename: Chihiro
authors.initials: C
authors.lastname: Ogawa
authors.forename: Amadu
authors.initials: A
authors.lastname: Jalloh
authors.forename: Yukari
authors.initials: Y
authors.lastname: Takahashi
authors.forename: Yuki
authors.initials: Y
authors.lastname: Kawai
authors.forename: Satomi
authors.initials: S
authors.lastname: Saga
authors.forename: Eiji
authors.initials: E
authors.lastname: Hayashi
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Ban
authors.forename: Shinyu
authors.initials: S
authors.lastname: Izumi
authors.forename: Akira
authors.initials: A
authors.lastname: Wada
authors.forename: Masayuki
authors.initials: M
authors.lastname: Mano
authors.forename: Megumu
authors.initials: M
authors.lastname: Fukunaga
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Kijima
authors.forename: Masashi
authors.initials: M
authors.lastname: Shiomi
authors.forename: Kaoru
authors.initials: K
authors.lastname: Inoue
authors.forename: Takeshi
authors.initials: T
authors.lastname: Hata
authors.forename: Yukihiro
authors.initials: Y
authors.lastname: Koretsune
authors.forename: Koichiro
authors.initials: K
authors.lastname: Kudo
authors.forename: Yuji
authors.initials: Y
authors.lastname: Himeno
authors.forename: Aizan
authors.initials: A
authors.lastname: Hirai
authors.forename: Kazuo
authors.initials: K
authors.lastname: Takahashi
authors.forename: Yuko
authors.initials: Y
authors.lastname: Sakai-Tagawa
authors.forename: Kiyoko
authors.initials: K
authors.lastname: Iwatsuki-Horimoto
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Kawaoka
authors.forename: Yoshihide
authors.initials: Y
authors.lastname: Hayashizaki
authors.forename: Toshihisa
authors.initials: T
authors.lastname: Ishikawa
mesh_terms: D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D000998:Antiviral Agents / Q000494:pharmacology; D001499:Bayes Theorem; D016000:Cluster Analysis; D004252:DNA Mutational Analysis; D024882:Drug Resistance, Viral / Q000235:genetics; D006389:Hemagglutinins, Viral / Q000737:chemistry / Q000145:classification / Q000235:genetics; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000187:drug effects / Q000235:genetics* / Q000302:isolation & purification; D007251:Influenza, Human / Q000453:epidemiology / Q000821:virology*; D007564:Japan / Q000453:epidemiology; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009154:Mutation; D009439:Neuraminidase / Q000737:chemistry / Q000145:classification / Q000235:genetics; D053139:Oseltamivir / Q000494:pharmacology; D058873:Pandemics; D010802:Phylogeny; D011487:Protein Conformation; D055503:Protein Multimerization; D012621:Seasons; D014764:Viral Proteins / Q000737:chemistry / Q000145:classification / Q000235:genetics*
chemical_list: D000998:Antiviral Agents; D006389:Hemagglutinins, Viral; D014764:Viral Proteins; D053139:Oseltamivir; D009439:Neuraminidase