State Key Laboratory for Molecular Virology and Genetic Engineering, Institute of Pathogen Biology, Chinese Academy Medical Sciences & Peking Union Medical College, No 6, Rongjing Road, Economic and Technological Development Zone, Beijing 100076, People’s Republic of China.
J Clin Microbiol. 2011 Jul;49(7):2426-34. doi: 10.1128/JCM.00007-11. Epub 2011 May 4.
Coxsackievirus (CV) strains CVA2, CVA4, CVA5, and CVA10 were isolated from patients with hand, foot, and mouth disease during a 2009 outbreak in China. Full genome sequences for four representative strains, CVA2/SD/CHN/09 (A2SD09), CVA4/SZ/CHN/09 (A4SZ09), CVA5/SD/CHN/09 (A5SD09), and CVA10/SD/CHN/09 (A10SD09), were determined. Phylogenetic and recombination analyses of the isolates by comparison with human enterovirus A prototype strains revealed that genetic recombination occurred during cocirculation of the viruses. The A2SD09 and A4SZ09 strains were most closely related to their corresponding prototype strains in the capsid region but shared noncapsid sequences with each other. Similarly, strains A5SD09 and A10SD09 had serotype-specific homology for the capsid proteins but shared noncapsid sequences with each other. Phylogenetic analyses of the four isolates with homotypic strains showed that CVA2 strains were divided into five genotypes. The A2SD09 strain clustered with Mongolia strains isolated in 2003, forming genotype V. The A4SZ09 strain and other isolates from mainland China and Taiwan clustered with genotype III strains and are likely related to strains that circulated in Europe and Mongolia. The A5SD09 strain is closely related to other Chinese strains isolated in 2008. The A10SD09 isolate, together with other Chinese strains isolated since 2004, formed a distinct lineage that was likely imported from Japan and South Korea. This study shows that natural recombination is a frequent event in human enterovirus A evolution. More comprehensive surveillance of enteroviruses that focus not only on EV71 or CVA16 is needed for us to understand the molecular epidemiology of enteroviruses and to track recombination events which may ultimately affect the virulence of viruses during outbreaks.
柯萨奇病毒（CV）株 CVA2、CVA4、CVA5 和 CVA10 是从中国 2009 年手足口病患者中分离出来的。对 4 株代表株，即 CVA2/SD/CHN/09（A2SD09）、CVA4/SZ/CHN/09（A4SZ09）、CVA5/SD/CHN/09（A5SD09）和 CVA10/SD/CHN/09（A10SD09）的全基因组序列进行了测定。通过与人类肠道病毒 A 原型株的比较，对分离株进行了系统进化和重组分析，结果表明，这些病毒在共同传播过程中发生了基因重组。A2SD09 和 A4SZ09 株在衣壳区与相应的原型株最为密切相关，但彼此之间存在非衣壳序列。同样，A5SD09 和 A10SD09 株在衣壳蛋白上具有血清型特异性同源性，但彼此之间存在非衣壳序列。对 4 株同源株的系统进化分析表明，CVA2 株分为 5 个基因型。A2SD09 株与 2003 年从蒙古分离的株聚在一起，形成了 V 型。A4SZ09 株和中国大陆及台湾的其他分离株与 III 型株聚在一起，可能与在欧洲和蒙古流行的株有关。A5SD09 株与其他中国 2008 年分离的株密切相关。A10SD09 分离株与自 2004 年以来从中国分离的其他株形成一个独特的分支，可能是从日本和韩国输入的。本研究表明，自然重组是人类肠道病毒 A 进化过程中的一个常见事件。我们需要更全面地监测肠道病毒，不仅要关注 EV71 或 CVA16，以便了解肠道病毒的分子流行病学，并跟踪重组事件，这可能最终影响病毒在暴发期间的毒力。
