title: Frequency of D222G and Q223R hemagglutinin mutants of pandemic (H1N1) 2009 influenza virus in Japan between 2009 and 2010.
abstract: BACKGROUND
  In April 2009, a novel swine-derived influenza A virus (H1N1pdm) emerged and rapidly spread around the world, including Japan. It has been suggested that the virus can bind to both 2,3- and 2,6-linked sialic acid receptors in infected mammals, in contrast to contemporary seasonal H1N1 viruses, which have a predilection for 2,6-linked sialic acid.
  
  
  RESULTS
  To elucidate the existence and transmissibility of α2,3 sialic acid-specific viruses in H1N1pdm, amino acid substitutions within viral hemagglutinin molecules were investigated, especially D187E, D222G, and Q223R, which are related to a shift from human to avian receptor specificity. Samples from individuals infected during the first and second waves of the outbreak in Japan were examined using a high-throughput sequencing approach. In May 2009, three specimens from mild cases showed D222G and/or Q223R substitutions in a minor subpopulation of viruses infecting these individuals. However, the substitutions almost disappeared in the samples from five mild cases in December 2010. The D187E substitution was not widespread in specimens, even in May 2009.
  
  
  CONCLUSIONS
  These results suggest that α2,3 sialic acid-specific viruses, including G222 and R223, existed in humans as a minor population in the early phase of the pandemic, and that D222 and Q223 became more dominant through human-to-human transmission during the first and second waves of the epidemic. These results are consistent with the low substitution rates identified in seasonal H1N1 viruses in 2008.
authors.affiliation: International Research Center for Infectious Diseases, Research Institute for Microbial Diseases (RIMD), Osaka University, Suita, Osaka, Japan.
authors.forename: Mayo
authors.initials: M
authors.lastname: Yasugi
authors.forename: Shota
authors.initials: S
authors.lastname: Nakamura
authors.forename: Tomo
authors.initials: T
authors.lastname: Daidoji
authors.forename: Norihito
authors.initials: N
authors.lastname: Kawashita
authors.forename: Ririn
authors.initials: R
authors.lastname: Ramadhany
authors.forename: Cheng-Song
authors.initials: CS
authors.lastname: Yang
authors.forename: Teruo
authors.initials: T
authors.lastname: Yasunaga
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Iida
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Horii
authors.forename: Kazuyoshi
authors.initials: K
authors.lastname: Ikuta
authors.forename: Kazuo
authors.initials: K
authors.lastname: Takahashi
authors.forename: Takaaki
authors.initials: T
authors.lastname: Nakaya
mesh_terms: D000595:Amino Acid Sequence; D019943:Amino Acid Substitution / Q000235:genetics*; D000818:Animals; D001665:Binding Sites; D002460:Cell Line; D002642:Chick Embryo; D004285:Dogs; D006386:Hemagglutination Tests; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000235:genetics*; D007564:Japan / Q000453:epidemiology; D008969:Molecular Sequence Data; D050505:Mutant Proteins / Q000737:chemistry; D059645:Mutation Rate; D009666:Nose / Q000382:microbiology; D010063:Ovum / Q000821:virology; D058873:Pandemics; D011991:Receptors, Virus / Q000378:metabolism; D016415:Sequence Alignment; D020539:Sequence Analysis, Protein; D012692:Serial Passage; D013048:Specimen Handling
chemical_list: D019267:Hemagglutinin Glycoproteins, Influenza Virus; D050505:Mutant Proteins; D011991:Receptors, Virus