Department of Pediatrics, Faculty of Medicine, Center of Excellence in Clinical Virology, Chulalongkorn University, Bangkok, Thailand.
FRS(T), The Royal Society of Thailand , Sanam Sueapa, Dusit, Bangkok, Thailand.
Sci Rep. 2024 Nov 6;14(1):26902. doi: 10.1038/s41598-024-77832-6.
Coxsackievirus A4 (CVA4) has recently become one of the most common causative agents of hand, foot, and mouth disease. The current study investigated the genetic diversity and spread of recombinant CVA4 by analyzing circulating genotypes and recombinant strains in Bangkok, Thailand, from 2017 to 2023. Partial VP1, 3Dpol, and whole genome sequencing of CVA4 samples collected from collaborating hospitals were conducted. Phylogenetic analysis of CVA4 VP1 and 3Dpol genome regions revealed discordance, indicating recombination. The predominant CVA4 genotype was C3, primarily observed in 2019. The predominant genotype in 2017 was C1. D2, commonly found in China, was occasionally observed. In nucleotide similarity analysis, intertypic recombination between CVA4 and EV-A during the evolutionary history of the virus was evident, particularly in the nonstructural region. The estimated emergence of genotypes C1 and C3 in Thailand occurred around 2014, with an evolutionary rate of 5.8 × 10 nucleotide substitutions per site per year. Genotype D2 exhibited notable variability across both the entire genome and the structural protein region compared to genotype C. Monitoring the genetic diversity and circulation of recombinant CVA4 is crucial for identifying newly emerging virus strains, enabling prompt public health responses and containment efforts, and enhancing surveillance in Thailand.
柯萨奇病毒 A4 型（CVA4）已成为手足口病的主要病原体之一。本研究通过分析 2017 年至 2023 年在泰国曼谷流行的基因型和重组株，探讨了 CVA4 的遗传多样性和传播情况。对合作医院采集的 CVA4 样本进行部分 VP1、3Dpol 和全基因组测序。CVA4 VP1 和 3Dpol 基因组区的系统进化分析显示存在不一致性，表明存在重组。主要流行的 CVA4 基因型为 C3，主要发生在 2019 年。2017 年主要流行的基因型是 C1。D2 型在中国较为常见，偶尔会出现。在核苷酸相似性分析中，病毒进化过程中 CVA4 与 EV-A 之间存在明显的异型重组，尤其是在非结构区。泰国 C1 和 C3 基因型的估计出现时间约为 2014 年，每年每个位点的核苷酸取代率为 5.8×10。与基因型 C 相比，基因型 D2 在整个基因组和结构蛋白区都表现出显著的变异性。监测重组 CVA4 的遗传多样性和传播对于识别新出现的病毒株至关重要，能够及时采取公共卫生应对措施和遏制措施，并加强泰国的监测。
