Evolutionary and Genetic Recombination Analyses of Coxsackievirus A6 Variants Associated with Hand, Foot, and Mouth Disease Outbreaks in Thailand between 2019 and 2022

Viruses. 2022 Dec 27;15(1):73. doi: 10.3390/v15010073.


Coxsackievirus (CV)-A6 infections cause hand, foot, and mouth disease (HFMD) in children and adults. Despite the serious public health threat presented by CV-A6 infections, our understanding of the mechanisms by which new CV-A6 strains emerge remains limited. This study investigated the molecular epidemiological trends, evolutionary dynamics, and recombination characteristics of CV-A6-associated HFMD in Thailand between 2019 and 2022. In the HFMD patient samples collected during the 4-year study period, we identified enterovirus (EV) RNA in 368 samples (48.7%), of which CV-A6 (23.7%) was the predominant genotype, followed by CV-A4 (6%), EV-A71 (3.7%), and CV-A16 (3.4%). According to the partial viral protein (VP) 1 sequences, all these CV-A6 strains belonged to the D3 clade. Based on the viral-RNA-dependent RNA polymerase (RdRp) gene, four recombinant forms (RFs), RF-A (147, 84.5%), RF-N (11, 6.3%), RF-H (1, 0.6%), and newly RF-Y (15, 8.6%), were identified throughout the study period. Results from the similarity plot and bootscan analyses revealed that the 3D polymerase (3Dpol) region of the D3/RF-Y subclade consists of sequences highly similar to CV-A10. We envisage that the epidemiological and evolutionarily insights presented in this manuscript will contribute to the development of vaccines to prevent the spread of CV-A6 infection.

Keywords: complete genome sequencing; coxsackievirus A6; evolution; genetic recombination; hand, foot, and mouth disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antibodies, Viral / genetics
  • Biological Evolution
  • Child
  • China / epidemiology
  • Disease Outbreaks
  • Enterovirus A, Human* / genetics
  • Enterovirus* / genetics
  • Genotype
  • Hand, Foot and Mouth Disease* / epidemiology
  • Humans
  • Recombination, Genetic
  • Thailand / epidemiology


  • Antibodies, Viral

Grants and funding

This research was funded by the National Research Council of Thailand, the Center of Excellence in Clinical Virology at Chulalongkorn University, the King Chulalongkorn Memorial Hospital, the MK Restaurant Group x Aunt Thongkam Foundation, and the BJC Big C Foundation. The Rachadapisek Sompote Fund of Chulalongkorn University awarded postdoctoral fellowships to Jiratchaya Puenpa.