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Genetic diversity and evolution of enterovirus A71 subgenogroup C1 from children with hand, foot, and mouth disease in Thailand

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Abstract

Enterovirus A71 (EV-A71) can cause hand, foot, and mouth disease (HFMD) in children and may be associated with severe neurological complications. There have been numerous reports of increased incidence of EV-A71 subgenogroup C1 (EV-A71 C1) infections associated with neurological diseases since the first occurrence in Germany in 2015. Here, we describe 11 full-length genome sequences of 2019 EV-A71 C1 strains isolated from HFMD patients in Thailand from 2019 to early 2020. The genetic evolution of 2019 EV-A71 C1 was traced in the outbreaks, and the emergence of multiple lineages was detected. Our results demonstrated that 2019 EV-A71 C1 from Thailand emerged through recombination between its nonstructural protein gene and those of other EV-A genotypes. Bayesian-based phylogenetic analysis showed that the 2019 EV-A71 C1 Thai strains share a common ancestor with variants in Europe (Denmark and France). The substitution rate for the 2019 EV-A71 C1 genome was estimated to be 4.38 × 10−3 substitutions/(site∙year−1) (95% highest posterior density interval: 3.84–4.94 × 10−3 substitutions/[site∙year−1]), approximating that observed between previous EV-A71 C1 outbreaks. These data are essential for understanding the evolution of EV-A C1 during the ongoing HFMD outbreak and may be relevant to disease outcomes in children worldwide.

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Acknowledgements

This study was funded by the project of Thailand Grand Challenge of National Research Council of Thailand, the Research Chair Grant from the National Science and Technology Development Agency (P-15-5004), the Center of Excellence in Clinical Virology at Chulalongkorn University, King Chulalongkorn Memorial Hospital, and the Rachadapisek Sompote Fund of Chulalongkorn University, which provided postdoctoral fellowships to Jiratchaya Puenpa.

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Authors and Affiliations

  1. Department of Pediatrics, Faculty of Medicine, Center of Excellence in Clinical Virology, Chulalongkorn University, Bangkok, Thailand

    Jiratchaya Puenpa, Jira Chansaenroj, Chompoonut Auphimai, Nasamon Wanlapakorn, Sompong Vongpunsawad & Yong Poovorawan

  2. Department of Microbiology, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand

    Kamol Suwannakarn

  3. Division of Academic Affairs, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand

    Nasamon Wanlapakorn

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  1. Jiratchaya Puenpa
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Contributions

JP analyzed data and drafted the manuscript. KS performed sequence analysis and edited the manuscript. JC and CA collected data and performed genome sequencing. NW, SV and YP supervised the study and finalized the manuscript. All authors reviewed the manuscript.

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Correspondence to Yong Poovorawan.

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The authors declare no competing interests.

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The research proposal was approved by the Institutional Review Board of the Ethics Committee of the Faculty of Medicine, Chulalongkorn University, Thailand (IRB number 286/58). The institutional review board of the Ethics Committee for human research waived the need for consent because all samples were anonymous. All methods were performed in accordance with the relevant guidelines and regulations.

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Puenpa, J., Suwannakarn, K., Chansaenroj, J. et al. Genetic diversity and evolution of enterovirus A71 subgenogroup C1 from children with hand, foot, and mouth disease in Thailand. Arch Virol 166, 2209–2216 (2021). https://doi.org/10.1007/s00705-021-05130-x

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