title: Circulating pattern and genomic characteristics of influenza B viruses in Taiwan from 2003 to 2014.
abstract: OBJECTIVE
  Influenza B viruses are antigenically classified into Yamagata and Victoria lineages according to their hemagglutinin (HA) proteins. These two lineages are known to either appear sequentially or cocirculate in Taiwan.
  
  
  METHODS
  Taiwanese influenza B viral HA and neuraminidase (NA) sequences between 2003 and 2014 were determined and analyzed. A time-scaled phylogenetic tree was constructed to decipher the evolutionary trends of these sequences, and the reassortment between the two lineages. Positively selected amino acids were predicted, demonstrating the adaptive mutations of the circulating pattern.
  
  
  RESULTS
  The HA phylogenetic tree revealed that the Victoria lineage evolved into a ladder-like pattern, whereas the Yamagata lineage exhibited complex topology with several independently evolved clades on which viruses from different influenza seasons interlaced. For several seasons, HA sequences were found to be dominated by strains of the same lineage as the corresponding vaccine strain. Inspecting these sequences revealed that frequent mutations occurred in neutralizing epitopes and glycosylation sites. Amino acid positions 212 and 214 of N-glycosylation sites, which are known to be critical determinants of receptor-binding specificity, were found to be subject to positive selection. No drug-resistant sites were noticed in the NA sequences. In addition, we identified several cases of NA reassortment with an overall incidence rate of 6% for the investigated Taiwan strains.
  
  
  CONCLUSIONS
  We highlighted the interplay between mutations in the glycosylation sites and epitope during HA evolution. These are crucial molecular signatures to be monitored for influenza B epidemics in the future.
authors.affiliation: Research Center for Emerging Viral Infections, College of Medicine, Chang Gung University, Taoyuan City, Taiwan.
authors.forename: Shu-Ming
authors.initials: SM
authors.lastname: Kuo
authors.affiliation: Research Center for Emerging Viral Infections, College of Medicine, Chang Gung University, Taoyuan City, Taiwan; Department of Computer Science and Information Engineering, School of Electrical and Computer Engineering, College of Engineering, Chang Gung University, Taoyuan City, Taiwan. Electronic address: gwchen@mail.cgu.edu.tw.
authors.forename: Guang-Wu
authors.initials: GW
authors.lastname: Chen
authors.affiliation: Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan City, Taiwan.
authors.forename: Arul Balaji
authors.initials: AB
authors.lastname: Velu
authors.affiliation: Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan City, Taiwan.
authors.forename: Srinivas
authors.initials: S
authors.lastname: Dash
authors.affiliation: Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan City, Taiwan.
authors.forename: Yi-Ju
authors.initials: YJ
authors.lastname: Han
authors.affiliation: Clinical Virology Laboratory, Linkou Chang Gung Memorial Hospital, Taoyuan City, Taiwan.
authors.forename: Kuo-Chien
authors.initials: KC
authors.lastname: Tsao
authors.affiliation: Research Center for Emerging Viral Infections, College of Medicine, Chang Gung University, Taoyuan City, Taiwan; Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan City, Taiwan; Clinical Virology Laboratory, Linkou Chang Gung Memorial Hospital, Taoyuan City, Taiwan. Electronic address: srshih@mail.cgu.edu.tw.
authors.forename: Shin-Ru
authors.initials: SR
authors.lastname: Shih
mesh_terms: D023281:Genomics; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000235:genetics*; D006801:Humans; D009981:Influenza B virus / Q000235:genetics* / Q000302:isolation & purification*; D007251:Influenza, Human / Q000453:epidemiology* / Q000821:virology; D009154:Mutation; D009439:Neuraminidase / Q000235:genetics*; D010802:Phylogeny; D012367:RNA, Viral / Q000032:analysis; D017423:Sequence Analysis, RNA; D013624:Taiwan / Q000453:epidemiology
chemical_list: D019267:Hemagglutinin Glycoproteins, Influenza Virus; D012367:RNA, Viral; C493831:hemagglutinin HA1, influenza B virus; D009439:Neuraminidase
keywords: evolution; glycosylation site; hemagglutinin; influenza B virus; neuraminidase reassortment