Genome Analysis of Coxsackievirus A4 Identified from Herpangina Children in Northern China

Sporadic epidemics of coxsackievirus A4 (CVA4) have been reported worldwide. However, the lack of the whole genome sequence has restricted the study of the gene characterization and evolution of CVA4. In this study, four whole genome sequences and 17 VP1 sequences of CVA4 identified from Linyi, northern China, in summer 2024 were used for genetic characterization and phylogenetic analysis. Four genotypes (A, B, C, and D) and five subgenotypes (C1-C5) were identified based on VP1 sequences. The Linyi CVA4 strains belong to subgenotype C2, which has also been the main prevalent subgenotype in China in recent years. The Linyi CVA4 strains exhibited high homology with the CVA4 prototype strain in the P1 region while exhibited higher homology with some non-CVA4 EV-A strains identified in China, including five CVA2 strains, three CVA5 strains, three CVA6 strains, one CVA8 strain, one CVA12 strain, and one CVA14 strain in the P2 and P3 regions. Recombination analysis of the whole genome sequences of the Linyi CV4 strains revealed that two Linyi CVA4 strains might be recombinants of one Shanghai CVA4 strain (KJ541163) and one Jiangsu CVA2 strain (OL519580). One Linyi CVA4 strain might be a recombinant of one Shandong CVA2 strain (MK967660) and one Shanghai CVA4 strain (KJ541163).