title: Emergence and transmission pathways of rapidly evolving evolutionary branch C4a strains of human enterovirus 71 in the Central Plain of China.
abstract: BACKGROUND
  Large-scale outbreaks of hand, foot, and mouth disease (HFMD) occurred repeatedly in the Central Plain of China (Shandong, Anhui, and Henan provinces) from 2007 until now. These epidemics have increased in size and severity each year and are a major public health concern in mainland China.
  
  
  RESULTS
  Phylogenetic analysis was performed and a Bayesian Markov chain Monte Carlo tree was constructed based on the complete VP1 sequences of HEV71 isolates. These analyses showed that the HFMD epidemic in the Central Plain of China was caused by at least 5 chains of HEV71 transmission and that the virus continued to circulate and evolve over the winter seasons between outbreaks. Between 1998 and 2010, there were 2 stages of HEV71 circulation in mainland China, with a shift from evolutionary branch C4b to C4a in 2003-2004. The evolution rate of C4a HEV71 was 4.99×10(-3) substitutions per site per year, faster than the mean of all HEV71 genotypes. The most recent common ancestor estimates for the Chinese clusters dated to October 1994 and November 1993 for the C4a and C4b evolutionary branches, respectively. Compared with all C4a HEV71 strains, a nucleotide substitution in all C4b HEV71 genome (A to C reversion at nt2503 in the VP1 coding region, which caused amino acid substitution of VP1-10: Gln to His) had reverted.
  
  
  CONCLUSIONS
  The data suggest that C4a HEV71 strains introduced into the Central Plain of China are responsible for the recent outbreaks. The relationships among HEV71 isolates determined from the combined sequence and epidemiological data reveal the underlying seasonal dynamics of HEV71 circulation. At least 5 HEV71 lineages circulated in the Central Plain of China from 2007 to 2009, and the Shandong and Anhui lineages were found to have passed through a genetic bottleneck during the low-transmission winter season.
authors: WHO WPRO Regional Polio Reference Laboratory and State Key Laboratory for Molecular Virology and Genetic Engineering, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, People's Republic of China.
authors: Yong
authors: Y
authors: Zhang
authors: Jitao
authors: J
authors: Wang
authors: Wanshen
authors: W
authors: Guo
authors: Haiyan
authors: H
authors: Wang
authors: Shuangli
authors: S
authors: Zhu
authors: Dongyan
authors: D
authors: Wang
authors: Ruyin
authors: R
authors: Bai
authors: Xingle
authors: X
authors: Li
authors: Dongmei
authors: D
authors: Yan
authors: Huiling
authors: H
authors: Wang
authors: Yan
authors: Y
authors: Zhang
authors: Zhen
authors: Z
authors: Zhu
authors: Xiaojuan
authors: X
authors: Tan
authors: Hongqiu
authors: H
authors: An
authors: Aiqiang
authors: A
authors: Xu
authors: Wenbo
authors: W
authors: Xu
mesh_terms: D001499:Bayes Theorem; D036022:Capsid Proteins / Q000235:genetics; D002681:China / Q000453:epidemiology; D004196:Disease Outbreaks; D029821:Enterovirus A, Human / Q000145:classification / Q000235:genetics*; D019143:Evolution, Molecular; D016679:Genome, Viral / Q000235:genetics; D005838:Genotype; D006232:Hand, Foot and Mouth Disease / Q000453:epidemiology* / Q000635:transmission* / Q000821:virology; D006801:Humans; D008390:Markov Chains; D008969:Molecular Sequence Data; D009010:Monte Carlo Method; D009154:Mutation; D010802:Phylogeny; D017422:Sequence Analysis, DNA; D013045:Species Specificity
chemical_list: D036022:Capsid Proteins; C442501:VP1 protein, Foot-and-mouth disease virus