Zhang Xuejie, Li Renqing, Lu Roujian, Wu Changcheng, Liang Zhichao, Zhang Zhongxian, Huang Baoying, Yang Yang, Qi Zhenyong, Zhang Daitao, Zhai Desheng, Wang Quanyi, Tan Wenjie
School of Public Health, Xinxiang Medical University, No. 601 Jinsui Avenue, Hongqi District, Xinxiang 453003, Henan, China.
Institute for Infectious Disease and Endemic Disease Control, Beijing Center for Disease Prevention and Control, No. 16 Hepingli Middle Road, Dongcheng District, Beijing 100013, China.
Virus Evol. 2025 May 11;11(1):veaf036. doi: 10.1093/ve/veaf036. eCollection 2025.
Coxsackievirus A6 (CVA6) is a major pathogen responsible for numerous outbreaks of hand, foot, and mouth disease (HFMD) worldwide. This study investigates the molecular evolution and recombination of CVA6 in Beijing, China. Full-length sequences of 54 CVA6 from Beijing (2019-2023) were obtained through metagenomic next-generation sequencing and Sanger sequencing. These sequences were compared with representative sequences from GenBank to analyse their phylogenetic characteristics, recombination diversity, and evolutionary dynamics. The 54 CVA6 strains co-circulated with those from multiple provinces in China, as well as from South Korea and Japan. Phylogenetic analysis revealed a novel D3c branch, with the VP1 T283A amino acid mutation identified as a key change in its formation. One sequence belonged to the D3a branch, while 53 sequences belonged to the D3c branch. Recombination analysis identified RF-A (46, 85.1%) and three novel recombinant forms (RFs): RF-Z (1, 1.9%), RF-AA (1, 1.9%), and RF-AB (6, 11.1%). Bayesian phylogenetic analysis estimated that the most recent common ancestor of D3c emerged in August 2013 (95% highest probability density (HPD): May 2012 to September 2014), with recombination events occurring in RF-Z (2017-2019), RF-AA (2019-2023), and RF-AB (2021-2023). In conclusion, we revealed a globally circulating CVA6 D3c branch and identified three novel RFs, providing valuable insights for the intervention and control of HFMD.
柯萨奇病毒A6（CVA6）是导致全球众多手足口病（HFMD）疫情的主要病原体。本研究调查了中国北京CVA6的分子进化和重组情况。通过宏基因组二代测序和桑格测序获得了2019 - 2023年来自北京的54株CVA6的全长序列。将这些序列与来自GenBank的代表性序列进行比较，以分析它们的系统发育特征、重组多样性和进化动态。这54株CVA6毒株与来自中国多个省份以及韩国和日本的毒株共同流行。系统发育分析揭示了一个新的D3c分支，其中VP1 T283A氨基酸突变被确定为其形成的关键变化。1个序列属于D3a分支，53个序列属于D3c分支。重组分析确定了RF - A（46株，85.1%）和三种新的重组形式（RFs）：RF - Z（1株，1.9%）、RF - AA（1株，1.9%）和RF - AB（6株，11.1%）。贝叶斯系统发育分析估计，D3c的最近共同祖先出现在2013年8月（95%最高后验密度（HPD）：2012年5月至2014年9月），重组事件发生在RF - Z（2017 - 2019年）、RF - AA（2019 - 2023年）和RF - AB（2021 - 2023年）。总之，我们揭示了全球流行的CVA6 D3c分支并鉴定出三种新的RFs，为手足口病的干预和控制提供了有价值的见解。
