Genomic characteristics of coxsackievirus A8 strains associated with hand, foot, and mouth disease and herpangina

Coxsackievirus A8 (CV-A8), a member of the genus Enterovirus of the family Picornaviridae, can cause a variety of infectious diseases, such as hand, foot and mouth disease (HFMD), herpangina (HA), encephalitis, paralysis, myelitis, and meningitis. This is a first report of complete genome sequences of CV-A8 strains associated with HFMD/HA since the prototype strain Donovan was identified in 1949. The complete genome sequences of eight new CV-A8 strains showed 19.2 %-20.6 % nucleotide differences when compared to the prototype strain Donovan, and 81.5 %-99.9 % similarity to each other. The topology of a polyphyletic tree based on complete capsid protein gene sequences indicated that the new CV-A8 strains and Donovan are monophyletic. However, seven CV-A8 strains clustered with CV-A10 and CV-A2 in the 5'UTR and P2 region, respectively. In the P3 region, three and four CV-A8 strains grouped with CV-A6 and CV-A2, respectively. Seven CV-A8 strains segregated from Donovan and grouped in a separate lineage in the 3'UTR. The strain CVA8/SZ266/CHN/2014 was most similar to EV71 in the nonstructural proteins regions. Phylogenetic analysis classified worldwide CV-A8 isolates into four distinct clusters, and almost all Chinese and Thai CV-A8 strains evolved independently in their respective lineages, which indicated geographical evolution of CV-A8.