Genetic characteristics of Coxsackievirus A6 from children with hand, foot and mouth disease in Beijing, China, 2017–2019

Object: To investigate the evolutionary and genetic characteristics of Coxsackievirus A6 (CV-A6) which acted as the predominant pathogen of hand, foot and mouth disease (HFMD) in children in Beijing, China, during 2017–2019. Methods Throat swab specimens were collected for general Enterovirus (EV), EV-A71 and CV-A16 detection by Real-time PCR. These general EV-positive samples were identified by semi-nested RT-PCR method and sequencing. The CV-A6 VP1 gene and genome sequences were amplified sequenced. The phylogenetic, variation and recombination analyses were performed. Results A total of 1721 HFMD patients were enrolled in this study, with the male to female ratio of 1.62:1. The majority of cases were less than five years, which accounted for 73.50%. The overall detection rate of EV was 88.32% (1520/1721). A total of 8 EV types were identified (CV-A6 (55.86%), CV-A16 (26.32%), EV-A71 (2.24%), CV-A10 (2.04%), CV-A4 (1.05%), CV-A5 (0.59%), CV-A2 (0.33%), and CV-A8 (0.07%), while 175 (11.51%) EV were untyped. The main pathogen of HFMD is CV-A6 from 2017 to 2018, while CV-A6 and CV-A16 are the main causative pathogens in 2019. The nucleotide and amino acid sequence identities of the 120 CV-A6 complete VP1 gene sequences in this study were 91.2–100.0% and 97.7–100.0%, respectively. Compared with the prototype strain (Gdula) of CV-A6, the nucleotide and amino acid sequence identities were 81.7–84% and 94.7–96.3%, respectively. The phylogenetic tree indicated that all 120 CV-A6 sequences belonged to sub-genotype D3, while 119 CV-A6 sequences belonged to evolutionary branch D3a, except one from 2017 belonged to D3b. Recombination analyses based on the complete genome sequences showed that potential multiple recombination may have occurred in 2B and 3D protein coding regions with EV-A114. Conclusions The main pathogens of HFMD were CV-A6 and CV-A16 in Beijing, China between 2017 and 2019; while these CV-A6, as recombination strains, belonged to the D3a evolutionary branch.