Complete genome analysis demonstrates multiple introductions of enterovirus 71 and coxsackievirus A16 recombinant strains into Thailand during the past decade

Abstract

Hand, foot, and mouth disease (HFMD) caused by enteroviruses remains a public health threat, particularly in the Asia-Pacific region during the past two decades. Moreover, the introduction of multiple subgenotypes and the emergence of recombinant viruses is of epidemiological importance. Based on either the full genome or VP1 sequences, 32 enteroviruses (30 from HFMD patients, 1 from an encephalitic patient, and 1 from an asymptomatic contact case) isolated in Thailand between 2006 and 2014 were identified as 25 enterovirus 71 (EV71) isolates (comprising 20 B5, 1 C2, 2 C4a, and 2 C4b subgenotypes) and 7 coxsackievirus A16 (CA16) isolates (comprising 6 B1a and 1 B1b subgenotypes). The EV71 subgenotype C4b was introduced into Thailand for the first time in 2006 and was replaced by subgenotype C4a strains in 2009. Phylogenetic, similarity plot and bootscan analyses of the complete viral genomes identified 12 recombinant viruses among the 32 viral isolates. Only one EV71-B5 isolate out of 20 was a recombinant virus with one region of intratypic or intertypic recombination, while all four EV71-C4 isolates were recombinant viruses having undergone double recombination, and all seven CA16 isolates were recombinant viruses. The recombination breakpoints of these recombinants are located solely within the P2 and P3 regions. Surveillance for circulating strains and subgenotype replacement are important with respect to molecular epidemiology and the selection of the upcoming EV71 vaccine. In addition, the clinical importance of recombinant viruses needs to be further explored.

Acknowledgements

This work was supported by the National Science and Technology Development Agency. The authors would like to thank Prof. Duncan R. Smith from the Institute of Molecular Biosciences, Mahidol University for English editing of this paper.

Author contributions

P.P. conceived and designed the research study and wrote the paper; P.N. performed the experiments, analyzed the data, and wrote the paper; K.S. performed the experiments and analyzed the data; J.P. and C.K. performed the experiments; S.P. analyzed the data; R.B., A.M., A.T., and K.C. provided the clinical specimens for viral isolation. All authors read and approved the final version of the paper.

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary information

Supplementary Information accompanies this paper at (10.1038/s41426-018-0215-x).

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