title: Molecular evolution of HA gene of the influenza A H1N1 pdm09 strain during the consecutive seasons 2009-2011 in Hangzhou, China: several immune-escape variants without positively selected sites.
abstract: BACKGROUND
  Even under immune pressure, the highly active influenza A H1N1 pdm09 variants emerged again in December 2010. Did the variability lead to poor vaccine effectiveness?
  
  
  OBJECTIVE
  To study the genetic distance and antigenic drift of the influenza A H1N1 pdm09 strains based on the sequence analysis of HA virus gene segments during consecutive seasons 2009-2011 in Hangzhou, China.
  
  
  METHODS
  39 Clinical samples from influenza-like-illness patients with culture-confirmed influenza A H1N1 pdm09 infections were collected over seasons in routine influenza surveillance. The HA gene was amplified and sequenced. A perspective analysis of genetic distance, antigenic drift and positively selected sites were conducted.
  
  
  RESULTS
  Analyses of human influenza A H1N1 pdm09 strains isolated in Hangzhou revealed that during the seasons 2009-2011, the antigenic drift had occurred, away from the northern hemisphere 2010/2011 influenza vaccine strain A/California/07/2009. The 2010/2011 viruses cluster in two main branches with a significant genetic distance, characterized by either S202T and S468N, or K180T/I, V216A, P288S, I312V and I389F. Interestingly, the epitopes corresponding to the immune-escape characteristic have altered much, but none of the amino acid substitutions in 2010/2011 variants were positively selected.
  
  
  CONCLUSIONS
  The results of genetic surveillance in this study might account for frequent outbreaks of the influenza A H1N1 pdm09 strains since December 2010 and the disappearance after three months circulation. It facilitates early detection of antigenic sites for the virus to escape immunological restraint in 2010/2011 season. Continuous monitoring of antigenic changes is recommended.
authors.affiliation: Microbiology Laboratory, Hangzhou Center for Disease Control and Prevention, Zhejiang 310021, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Li
authors.forename: Tie-juan
authors.initials: TJ
authors.lastname: Shao
authors.forename: Xin-fen
authors.initials: XF
authors.lastname: Yu
authors.forename: Jin-cao
authors.initials: JC
authors.lastname: Pan
authors.forename: Xiao-ying
authors.initials: XY
authors.lastname: Pu
authors.forename: Hao-qiu
authors.initials: HQ
authors.lastname: Wang
authors.forename: Yu
authors.initials: Y
authors.lastname: Kou
mesh_terms: D000956:Antigens, Viral / Q000235:genetics*; D002681:China; D016000:Cluster Analysis; D019143:Evolution, Molecular; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000235:genetics*; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000235:genetics* / Q000302:isolation & purification; D007251:Influenza, Human / Q000821:virology*; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D010802:Phylogeny; D012367:RNA, Viral / Q000235:genetics; D017422:Sequence Analysis, DNA; D017385:Sequence Homology
chemical_list: D000956:Antigens, Viral; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D012367:RNA, Viral