title: Spatiotemporal phylogenetic analysis and molecular characterization of coxsackievirus A4.
abstract: Coxsackievirus A4 outbreaks occurred in Taiwan in 2004 and 2006. The spatiotemporal transmission of this error-prone RNA virus involves a continuous interaction between rapid sequence variation and natural selection. To elucidate the molecular characteristics of CV-A4 and the spatiotemporal dynamic changes in CV-A4 transmission, worldwide sequences of the 3' VP1 region (420 nt) obtained from GenBank were analyzed together with sequences isolated in Taiwan from 2002 to 2009. Sequences were characterized in terms of recombination, variability, and selection. Phylogenetic trees were constructed using neighbor-joining, maximum likelihood and Monte Carlo Markov Chain methods. Spatiotemporal dynamics of CV-A4 transmission were further estimated by a Bayesian statistical inference framework. No recombination was detected in the 420 nt region. The estimated evolution rate of CV-A4 was 8.65 × 10(-3) substitutions/site/year, and a purifying selection (d(N)/d(S)=0.032) was noted over the 3' VP1 region. All trees had similar topology: two genotypes (GI and GII), each including two subgenotypes (A and B), with the prototype and a Kenyan strain in separate branches. The results revealed that the virus first appeared in USA in 1950. Since 1998, it has evolved into the Kenya, GI-A (Asia) and GII-A (Asia and Europe) strains. Since 2004, GI-B and GII-B have evolved continuously and have remained prevalent. The co-existence of several positive selection lineages of GI-B in 2006 indicates that the subgenotype might have survived lineage extinction. This study revealed rapid lineage turnover of CV-A4 and the replacement of previously circulating strains by a new dominant variant. Therefore, continuous surveillance for further CV-A4 transmission is essential.
authors.affiliation: Department of Medical Laboratory Science and Biotechnology, College of Health Science, Kaohsiung Medical University, Kaohsiung, Taiwan. peiyuchu@kmu.edu.tw
authors.forename: Pei-Yu
authors.initials: PY
authors.lastname: Chu
authors.forename: Po-Liang
authors.initials: PL
authors.lastname: Lu
authors.forename: Yu-Ling
authors.initials: YL
authors.lastname: Tsai
authors.forename: Edward
authors.initials: E
authors.lastname: Hsi
authors.forename: Ching-Yuan
authors.initials: CY
authors.lastname: Yao
authors.forename: Yu-Hsien
authors.initials: YH
authors.lastname: Chen
authors.forename: Li-Ching
authors.initials: LC
authors.lastname: Hsu
authors.forename: Sheng-Yu
authors.initials: SY
authors.lastname: Wang
authors.forename: Ho-Sheng
authors.initials: HS
authors.lastname: Wu
authors.forename: Yi-Ying
authors.initials: YY
authors.lastname: Lin
authors.forename: Hui-Ju
authors.initials: HJ
authors.lastname: Su
authors.forename: Kuei-Hsiang
authors.initials: KH
authors.lastname: Lin
mesh_terms: D000595:Amino Acid Sequence; D002675:Child, Preschool; D004770:Enterovirus / Q000235:genetics*; D005260:Female; D006557:Herpangina / Q000453:epidemiology / Q000821:virology*; D006801:Humans; D007223:Infant; D008297:Male; D008969:Molecular Sequence Data; D010802:Phylogeny; D058974:Phylogeography; D011336:Probability; D011995:Recombination, Genetic; D017423:Sequence Analysis, RNA; D013624:Taiwan / Q000453:epidemiology; D014764:Viral Proteins / Q000235:genetics
chemical_list: D014764:Viral Proteins