Department of Medical Laboratory Science and Biotechnology, College of Health Science, Kaohsiung Medical University, Kaohsiung, Taiwan.
Infect Genet Evol. 2011 Aug;11(6):1426-35. doi: 10.1016/j.meegid.2011.05.010. Epub 2011 May 24.
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.
柯萨奇病毒 A4 于 2004 年和 2006 年在台湾爆发。这种易错 RNA 病毒的时空传播涉及快速序列变异和自然选择的持续相互作用。为了阐明 CV-A4 的分子特征以及 CV-A4 传播的时空动态变化，对从 GenBank 获得的 3'VP1 区域（420nt）的全球序列与 2002 年至 2009 年在台湾分离的序列进行了分析。对序列进行了重组、变异性和选择特征分析。使用邻接法、最大似然法和蒙特卡罗马尔可夫链方法构建了系统发育树。进一步通过贝叶斯统计推断框架估计了 CV-A4 的时空动态。在 420nt 区域未检测到重组。CV-A4 的估计进化率为 8.65×10(-3)替换/位点/年，并且在 3'VP1 区域观察到纯化选择（d(N)/d(S)=0.032）。所有树的拓扑结构相似：两种基因型（GI 和 GII），每个基因型包括两个亚基因型（A 和 B），原型和肯尼亚株在不同的分支中。结果表明，该病毒于 1950 年首次出现在美国。自 1998 年以来，它已演变成肯尼亚、GI-A（亚洲）和 GII-A（亚洲和欧洲）株。自 2004 年以来，GI-B 和 GII-B 不断进化并持续流行。2006 年 GI-B 的几个阳性选择谱系共存表明，亚基因型可能幸存下来并灭绝。本研究揭示了 CV-A4 的快速谱系更替以及新的优势变异株取代了先前流行的株系。因此，需要对进一步的 CV-A4 传播进行持续监测。
