Enterovirus A71 Phenotypes Causing Hand, Foot and Mouth Disease, Vietnam

Abstract

We investigated enterovirus A71-associated hand, foot and mouth disease in Vietnam and found that, after replacing subgenogroup C4 in 2013, B5 remained the leading cause of this disease. In contrast with previous observations, this switch did not result in an explosive outbreak, and B5 evolution was driven by negative selection.

Keywords: Enterovirus A71; Picornaviruses; Vietnam; hand foot and mouth disease; phenotypes; viruses.

Figure 1

Maximum-clade credibility tree illustrating results of phylogeographic analysis of enterovirus A71 subgenogroup B5 coding sequences, Vietnam, July 2013–April 2015. Black circles indicate posterior probabilities ≥70% and state probabilities ≥70% at all nodes. Branch colors represent sampling locations from 5 discrete states in Vietnam (inset map; https://mapchart.net). Small sample sizes from individual provinces precluded phylogeographic analyses at a finer spatial scale. Except for Ho Chi Minh City, we grouped provinces in Vietnam from which we sampled viruses into discrete locations, including southeast (Ba Ria, Binh Duong, Binh Phuoc, Dong Nai, Tay Ninh, and Vung Tau Provinces), Mekong Delta (Can Tho, Dong Thap, Hau Giang, Kien Giang, Long An, and Tien Giang Provinces), and Central Highlands (Dac Nong and Lam Dong Provinces). We analyzed whole-genome sequence data using general time reversible plus gamma 4 nt substitution models suggested by IQ-TREE version 1.4.3 (http://www.iqtree.org). Viral protein 1–based analysis yielded similar results (Appendix Figure 2). Enterovirus A71 sequences generated in this study were submitted to GenBank under accession nos. MH_716248–6393 and KP_691643–66.

Figure 2

Complete coding sequence–based Bayesian skyline plot illustrating the relative genetic diversity of enterovirus A71 subgenogroup B5 in Vietnam over time. Black line indicates the mean; gray shading shows the upper and lower 95% highest posterior density values. Viral protein 1–based analysis yielded similar results (Appendix Figure 3f).