Sub-genotype change and recombination of coxsackievirus A6s may be the cause of it being the predominant pathogen for HFMD in children in Beijing, as revealed by analysis of complete genome sequences

Abstract

Objectives: To investigate why coxsackievirus A6 (CVA6) has replaced enterovirus A71 (EV71) and coxsackievirus A16 (CVA16), which used to be the most predominant etiological agents, for hand, foot and mouth disease (HFMD) in children in Beijing, China. Methods: Sixty-four CVA6-positive samples were identified from 2010 to 2016 and selected for whole genome sequence amplification and analysis. Results: It was demonstrated that the whole genome sequences of CVA6s in this study were 7432–7435 nucleotides in length, and the different lengths were only in the 5′UTR region. The phylogenetic tree analysis of the full-length VP1 region of CVA6s indicated that the prevalent CVA6s in Beijing changed from the previous D2 sub-genotype to the D3 sub-genotype in 2013. In this study, two recombinant forms (RFs)– RF-C and RF-D – of CVA6 mainly appeared in 2010 and 2011. Since 2013, three recombinant CVA6 variants – RF-A, J and L – have been prevalent in children with HFMD in Beijing. The recombination region of RF-J was located at the 2C region, while RF-L had a new recombination point in the 3D region. The recombination of prevalent CVA6s in Beijing from 2013 to 2016 occurred within non-capsid regions of the genome, especially the P2 and P3 regions. Conclusions: The sub-genotype change and recombination of CVA6s indicated from this study may explain why CVA6 has become the predominant pathogen causing HFMD since 2013.

Keywords

• Coxsackievirus A6
• Hand, foot and mouth disease
• Phylogenetic analysis
• Recombination