title: Molecular evolutionary analysis of the influenza A(H1N1)pdm, May-September, 2009: temporal and spatial spreading profile of the viruses in Japan.
abstract: BACKGROUND
  In March 2009, pandemic influenza A(H1N1) (A(H1N1)pdm) emerged in Mexico and the United States. In Japan, since the first outbreak of A(H1N1)pdm in Osaka and Hyogo Prefectures occurred in the middle of May 2009, the virus had spread over 16 of 47 prefectures as of June 4, 2009.
  
  
  RESULTS
  We analyzed all-segment concatenated genome sequences of 75 isolates of A(H1N1)pdm viruses in Japan, and compared them with 163 full-genome sequences in the world. Two analyzing methods, distance-based and Bayesian coalescent MCMC inferences were adopted to elucidate an evolutionary relationship of the viruses in the world and Japan. Regardless of the method, the viruses in the world were classified into four distinct clusters with a few exceptions. Cluster 1 was originated earlier than cluster 2, while cluster 2 was more widely spread around the world. The other two clusters (clusters 1.2 and 1.3) were suggested to be distinct reassortants with different types of segment assortments. The viruses in Japan seemed to be a multiple origin, which were derived from approximately 28 transported cases. Twelve cases were associated with monophyletic groups consisting of Japanese viruses, which were referred to as micro-clade. While most of the micro-clades belonged to the cluster 2, the clade of the first cases of infection in Japan originated from cluster 1.2. Micro-clades of Osaka/Kobe and the Fukuoka cases, both of which were school-wide outbreaks, were eradicated. Time of most recent common ancestor (tMRCA) for each micro-clade demonstrated that some distinct viruses were transmitted in Japan between late May and early June, 2009, and appeared to spread nation-wide throughout summer.
  
  
  CONCLUSIONS
  Our results suggest that many viruses were transmitted from abroad in late May 2009 irrespective of preventive actions against the pandemic influenza, and that the influenza A(H1N1)pdm had become a pandemic stage in June 2009 in Japan.
authors.affiliation: Infectious Diseases Surveillance Center, National Institute of Infectious Diseases, Tokyo, Japan.
authors.forename: Teiichiro
authors.initials: T
authors.lastname: Shiino
authors.forename: Nobuhiko
authors.initials: N
authors.lastname: Okabe
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Yasui
authors.forename: Tomimasa
authors.initials: T
authors.lastname: Sunagawa
authors.forename: Makoto
authors.initials: M
authors.lastname: Ujike
authors.forename: Masatsugu
authors.initials: M
authors.lastname: Obuchi
authors.forename: Noriko
authors.initials: N
authors.lastname: Kishida
authors.forename: Hong
authors.initials: H
authors.lastname: Xu
authors.forename: Emi
authors.initials: E
authors.lastname: Takashita
authors.forename: Akane
authors.initials: A
authors.lastname: Anraku
authors.forename: Reiko
authors.initials: R
authors.lastname: Ito
authors.forename: Teruko
authors.initials: T
authors.lastname: Doi
authors.forename: Miho
authors.initials: M
authors.lastname: Ejima
authors.forename: Hiromi
authors.initials: H
authors.lastname: Sugawara
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Horikawa
authors.forename: Shuji
authors.initials: S
authors.lastname: Yamazaki
authors.forename: Yumiko
authors.initials: Y
authors.lastname: Kato
authors.forename: Akio
authors.initials: A
authors.lastname: Oguchi
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Fujita
authors.forename: Takato
authors.initials: T
authors.lastname: Odagiri
authors.forename: Masato
authors.initials: M
authors.lastname: Tashiro
authors.forename: Haruo
authors.initials: H
authors.lastname: Watanabe
mesh_terms: D001499:Bayes Theorem; D016000:Cluster Analysis; D019143:Evolution, Molecular; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000302:isolation & purification*; D007251:Influenza, Human / Q000453:epidemiology* / Q000821:virology; D007564:Japan / Q000453:epidemiology