2011-2014年福建省手足口病相关病原柯萨奇病毒A组4型的分子流行病学分析

Molecular epidemiology of HFMD-associated pathogen coxsackievirus A4 in Fujian Province,2011-2014

目的分析福建省手足口病患者中柯萨奇病毒A组4型(Coxsackievirus A4,CVA4)的流行病学、基因变异及遗传进化等特征。方法应用细胞培养方法获得病毒分离株,RT-PCR方法进行分子分型及扩增CVA4血清型完整VP1区全长序列,并进行序列变异及遗传进化分析。结果 2011-2014年,从福建省手足口病其它肠道病毒病例标本中分子分型33例CVA4病例,在407例的其它肠道病毒病例中的构成比为8.1%,其中2012年31例,2014年2例。CVA4病例在性别、年龄组分布特征,与一般手足口病流行特征相比,没有特异性。VP1区序列差异比较表明,2011-2014年福建省CVA4分离株之间VP1核苷酸及氨基酸序列相似性分别在92.6%~100%、95.7%~100%;与原型株及国外地方株的核苷酸序列相似性较低,分别为83.7%~85.4%、82.1%~89.1%,氨基酸序列相似性分别为96.1%~99.0%、90.4%~99.6%;与国内地方株核苷酸及氨基酸序列相似性较高,分别为87.9%~99.2%、96.1%~100%。进化树结果表明福建CVA4分离株与原型株及国外代表株的遗传距离远,与国内代表株的遗传距离近。福建CVA4分离株在进化树的分布呈多个分支。结论 CVA4已成为近年来福建省除EV71、CVA16、CVA6、CVA10外导致手足口病的又一重要病原体。福建CVA4分离株与国内地方株同进化共循环,在福建省各个地区同时流行多条亲缘关系接近的传播链。

To analyze the epidemiology, genetic variation and genetic evolution of coxsackievirus A4 （CVA4） in patients with hand, foot and mouth disease in Fujian, the virus isolates were molecular typed and amplified the whole VP1 region by RT-PCR, then the genetic variation and evolution were studied. The results showed that 33 CVA4 cases （8. 1%） were con- firmed from the 407 non-EV71 non-CVA16 HFMD cases in F@ian Province during 2011 and 2014, accounting for 31 cases in 2012 and 2 cases in 2014. Compared with common characteristics of the HFMD epidemic, no specificity in the distribution of CVA4 cases was found between gender and age groups. Sequence analysis of VP1 nucleotide sequences of Fujian CVA4 isolates showed that the nucleotide and amino acid sequences similarity were 92.6%- 100% and 95.7 %- 100 % respectively, low simi- larity with the prototype （83.7%-85.4%, 96.1%-99.0%） and abroad isolates （82.1%-89.1Z%, 90.4% -99.6%） both in nucleotide and amino acid sequences, high similarity with domestic isolates both in nucleotide and amino acid sequences, with the similarity of 87.9%-99.2 and 96.1%-100%. The results from phylogenetic tree showed that the genetic distance be- tween Fujian CVA4 isolates and the prototype and abroad strains was far, and the genetic distance was close to domestic iso- lates in China. The distribution of the phylogenetic trees of Fujian CVA4 strains showed multiple branches. Therefore, CVA4 is the major HFMD associated-pathogen other than EV71, CVA 16, CVA6, and CVA10 in Fujian Province from 2011 to 2014.CVA4 strains from Fujian Province is co-circulating and co-e- volving with other domestic isolates. There is existence of multiple closely related CVA4 transmission chains in various regions of Fujian.