title: Population dynamics and genetic diversity of C4 strains of human enterovirus 71 in Mainland China, 1998-2010.
abstract: BACKGROUND
  Since 1997, several countries within the Asian Pacific region have been affected by one or more massive outbreaks of Hand Foot and Mouth Disease (HFMD). Virus typing experiments revealed that these outbreaks were caused by strains of human enterovirus 71 (EV71) belonging to several different, recently emerged subgenogroups. In mainland China, a different situation was observed. The first outbreak, localized in Shangdong Province, was reported in 2007, and was followed by a wide-spread outbreak in mainland China in 2008. Since then, numbers of reported HFMD cases have been persistently high.
  
  
  RESULTS
  To gain insight in the epidemiological behavior of EV71 in China, we studied genetic diversity and EV71 population dynamics to address whether the increase in number of reported EV71 infections reflects a real increase in viral spread or is just the result of increased awareness and surveillance. We used systematically collected VP1 gene sequences of 257 EV71 strains collected in Guangdong province from 2008 to 2010 as part of HFMD surveillance activities, and supplemented them with 305 GenBank EV71 reference stains collected in China from 1998 to 2010. All isolates from Guangdong Province belonged to subgenogroup C4. Viral population dynamics indicated that the increased reporting of HFMD in China since 2007 reflects a real increase in viral spread and continued replacement of viral lineages through time. Amino acid sequence comparisons revealed substitution of amino acid in residues 22, 145 and 289 through time regularly with the VP1 gene of EV71 strains isolated in mainland China from 1998 to 2010.
  
  
  CONCLUSIONS
  EV71 strains isolated in mainland China mainly belonged to subgenogroup C4. There was exponential growth of the EV71 virus population in 2007 and 2008. There was amino acid substitution through time regularly with the VP1 gene which possibly increased viral spread and/or ability of the virus to circulate persistently among the Chinese population.
authors.affiliation: Key Laboratory of Pathogen Detection for Emergency Response of Guangdong Province, Center for Disease Control and Prevention of Guangdong Province, Guangzhou, Guangdong, China.
authors.forename: Dawei
authors.initials: D
authors.lastname: Guan
authors.forename: Sabine
authors.initials: S
authors.lastname: van der Sanden
authors.forename: Hanri
authors.initials: H
authors.lastname: Zeng
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.forename: Huanying
authors.initials: H
authors.lastname: Zheng
authors.forename: Cong
authors.initials: C
authors.lastname: Ma
authors.forename: Juan
authors.initials: J
authors.lastname: Su
authors.forename: Zheng
authors.initials: Z
authors.lastname: Liu
authors.forename: Xue
authors.initials: X
authors.lastname: Guo
authors.forename: Xin
authors.initials: X
authors.lastname: Zhang
authors.forename: Leng
authors.initials: L
authors.lastname: Liu
authors.forename: Marion
authors.initials: M
authors.lastname: Koopmans
authors.forename: Changwen
authors.initials: C
authors.lastname: Ke
mesh_terms: D000465:Algorithms; D000595:Amino Acid Sequence; D001499:Bayes Theorem; D002681:China / Q000453:epidemiology; D004279:DNA, Viral; D004196:Disease Outbreaks; D029821:Enterovirus A, Human / Q000235:genetics* / Q000302:isolation & purification; D014644:Genetic Variation; D006232:Hand, Foot and Mouth Disease / Q000821:virology; D006801:Humans; D008969:Molecular Sequence Data; D009010:Monte Carlo Method; D009154:Mutation; D010802:Phylogeny; D017422:Sequence Analysis, DNA; D017386:Sequence Homology, Amino Acid
chemical_list: D004279:DNA, Viral