Genetic characteristics of Coxsackievirus A6 from children with hand, foot and mouth disease in Beijing, China, 2017-2019
Genetic characteristics of Coxsackievirus A6 from children with hand, foot and mouth disease in Beijing, China, 2017-2019
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DOI：
10.1016/j.meegid.2022.105378
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发表时间：
2022-10-26
影响因子：
3.2
通讯作者：
Xie, Zhengde
中科院分区：
文献类型：
--
作者：
Zhang, Meng;Chen, Xiangpeng;Xie, Zhengde
目的：调查2017-2019年北京儿童手足口病（HFMD）主要病原体柯萨奇病毒A6（CVA6）的进化和遗传特征。方法：采集咽拭子标本，采用实时荧光定量PCR检测普通肠道病毒（EV）、肠道病毒A71（EV-A71）和CVA16。这些普通EV阳性样本是通过半巢式RT-PCR方法和测序进行鉴定的。对 CVA6 VP1 基因和基因组序列进行扩增和测序。进行了系统发育、变异和重组分析。结果：共纳入1721例手足口病患者，男女比例为1.62：1。 5年以内的案件居多，占73.50%。 EV总体检出率为88.32%（1520/1721）。共鉴定出 8 种 EV 类型，包括 CVA6（55.86%）、CVA16（26.32%）、EV-A71（2.24%）、CVA10（2.04%）、CVA4（1.05%）、CVA5（0.59%）、CVA2（0.33%）和 CVA8（0.07%），而 175 (11.51%) EV 未定型。 2017-2018年手足口病的主要致病菌为CVA6，2019年的主要致病菌为CVA6和CVA16。本研究中120条CVA6完整VP1基因序列的核苷酸和氨基酸序列同一性分别为91.2%-100.0%和97.7%-100.0%。与CVA6原型菌株(Gdula)相比，核苷酸和氨基酸序列同一性分别为81.7%-84%和94.7%-96.3%。系统发育树表明，所有120个CVA6序列均属于亚基因型D3，而119个CVA6序列属于进化分支D3a，除了2017年的1个序列属于D3b。基于全基因组序列的重组分析表明，EV-A114的2B和3D蛋白编码区可能发生潜在的多重重组。结论：2017-2019年中国北京市手足口病的主要病原体为CVA6和CVA16；而这些CVA6作为重组株，属于D3a进化分支。
Object: To investigate the evolution and genetic characteristics of Coxsackievirus A6 (CVA6) which acted as the predominant pathogen of hand, foot and mouth disease (HFMD) in children in Beijing, China, 2017-2019. Methods: Throat swab specimens were collected for general Enterovirus (EV), enterovirus A71 (EV-A71) and CVA16 detection by Real-time PCR. These general EV-positive samples were identified by semi-nested RT-PCR method and sequencing. The CVA6 VP1 gene and genome sequences were amplified and sequenced. The phylogenetic, variation and recombination analyses were performed. Results: A total of 1721 HFMD patients were enrolled in this study, with the male to female ratio of 1.62:1. The majority of cases were less than five years, which accounted for 73.50%. The overall detection rate of EV was 88.32% (1520/1721). A total of 8 EV types were identified, including CVA6 (55.86%), CVA16 (26.32%), EV-A71 (2.24%), CVA10 (2.04%), CVA4 (1.05%), CVA5 (0.59%), CVA2 (0.33%), and CVA8 (0.07%), while 175 (11.51%) EV were untyped. The main pathogen of HFMD was CVA6 from 2017 to 2018, while CVA6 and CVA16 were the main causative pathogens in 2019. The nucleotide and amino acid sequence identities of the 120 CVA6 complete VP1 gene sequences in this study were 91.2%-100.0% and 97.7%-100.0%, respectively. Compared with the prototype strain (Gdula) of CVA6, the nucleotide and amino acid sequence identities were 81.7%-84% and 94.7%-96.3%, respectively. The phylogenetic tree indicated that all 120 CVA6 sequences belonged to sub-genotype D3, while 119 CVA6 sequences belonged to evolutionary branch D3a, except one from 2017 belonged to D3b. Recombination analysis based on the complete genome sequences showed that potential multiple recombination may have occurred in 2B and 3D protein coding regions with EV-A114.Conclusions: The main pathogens of HFMD were CVA6 and CVA16 in Beijing, China, 2017-2019; while these CVA6, as recombination strains, belonged to the D3a evolutionary branch.