Molecular epidemiology and the evolution of human coxsackievirus A6

Coxsackievirus A6 (CV-A6) is a major aetiologic agent for hand, foot and mouth disease (HFMD) in recent years. HFMD outbreaks associated with CV-A6 resulted from the evolutionary dynamics of CV-A6 and the appearance of novel recombinant forms (RFs). To examine this, 151 variants collected in 2013 and 2014 from Germany, Spain, Sweden, Denmark and Thailand were genotyped for the VP1 capsid and 3Dpol genes. Analysis of the VP1 gene showed an increasing correspondence between CV-A6 genome recombination and sequence divergence (estimated substitution rate of 8.1×10-3 substitutions site-1 year-1 and RF half-life of 3.1 years). Bayesian phylogenetic analysis showed that recent recombination groups (RF-E, -F, -H, -J and -K) shared a common ancestor (RF-A). Thirty-nine full-length genomes of different RFs revealed recombination breakpoints between the 2A-2C and the 5' UTRs. The emergence of new CV-A6 recombination groups has become widespread in Europe and Asia within the last 8 years.