title: Complete genome analysis of the C4 subgenotype strains of enterovirus 71: predominant recombination C4 viruses persistently circulating in China for 14 years.
abstract: Genetic recombination is a well-known phenomenon for enteroviruses. To investigate the genetic characterization and the potential recombination of enterovirus 71 (EV71) circulating in China, we determined the 16 complete genome sequences of EV71 isolated from Hand Foot Mouth Disease (HFMD) patients during the large scale outbreak and non-outbreak years since 1998 in China. The full length genome sequences of 16 Chinese EV71 in present study were aligned with 186 genome sequences of EV71 available from GenBank, including 104 China mainland and 82 international sequences, covering the time period of 1970-2011. The oldest strains of each subgenotype of EV71 and prototype strains of HEV-A were included to do the phylogenetic and Simplot analysis. Phylogenetic analysis indicated that all Chinese strains were clustered into C4 subgenotype of EV71, except for HuB/CHN/2009 clustered into A and Xiamen/CHN/2009 clustered into B5 subgenotype. Most of C4 EV71 were clustered into 2 predominant evolutionary branches: C4b and C4a evolutionary brunches. Our comprehensive recombination analysis showed the evidence of genome recombination of subgenotype C4 (including C4a and C4b) sequences between structural genes from genotype C EV71 and non-structural genes from the prototype strains of CAV16, 14 and 4, but the evidence of intratypic recombination between C4 strains and B subgenotype was not enough strong. This intertypic recombination C4 viruses were first seen in 1998 and became the predominant endemic viruses circulating in China mainland for at least 14 years. A shift between C4a and C4b evolutionary brunches of C4 recombination viruses were observed, and C4a viruses have been associated with large scale nationwide HFMD outbreak with higher morbidity and mortality since 2007.
authors: National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, People's Republic of China.
authors: Yan
authors: Y
authors: Zhang
authors: Xiaojuan
authors: X
authors: Tan
authors: Aili
authors: A
authors: Cui
authors: Naiying
authors: N
authors: Mao
authors: Songtao
authors: S
authors: Xu
authors: Zhen
authors: Z
authors: Zhu
authors: Jianhui
authors: J
authors: Zhou
authors: Jing
authors: J
authors: Shi
authors: Yueping
authors: Y
authors: Zhao
authors: Xianjun
authors: X
authors: Wang
authors: Xueyong
authors: X
authors: Huang
authors: Shuangli
authors: S
authors: Zhu
authors: Yong
authors: Y
authors: Zhang
authors: Wei
authors: W
authors: Tang
authors: Hua
authors: H
authors: Ling
authors: Wenbo
authors: W
authors: Xu
mesh_terms: D002681:China / Q000453:epidemiology; D029821:Enterovirus A, Human / Q000145:classification / Q000235:genetics*; D004769:Enterovirus Infections / Q000453:epidemiology / Q000635:transmission; D019143:Evolution, Molecular; D016679:Genome, Viral; D005838:Genotype; D006801:Humans; D008969:Molecular Sequence Data; D010641:Phenotype; D010802:Phylogeny; D011995:Recombination, Genetic