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| Genetic characteristics of the VP1 region of Coxsackievirus A4 from 1996 to 2024 |
| YAO Xuejun, CHEN Guoqing, XU Shilin, LI Changcheng
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| Yancheng Center for Disease Control and Prevention, Yancheng, Jiangsu 224000, China |
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Abstract Objective To analyze the genetic characteristics of the full-length nucleotide sequences in the VP1 region of Coxsackievirus A4 (CVA4) from 1996 to 2024, so as to provide the evidence for the prevention and control of hand, foot and mouth disease and herpangina, as well as for vaccine development. Methods The full-length VP1 nucleotide sequences of CVA4 isolates uploaded in China before December 16, 2025, were collected through the Enterovirus Database of the Bacterial and Viral Bioinformatics Resource Center. Genotypes, homology, sequence composition, evolutionary rate and high-frequency amino acid mutation sites were analyzed. Results A total of 423 full-length VP1 nucleotide sequences of CVA4 isolates from 27 provinces (autonomous regions and municipalities) in China from 1996 to 2024 were included. Among them, 377 strains were collected from 2010 to 2023, accounting for 89.13%; 234 strains were from the southwest region, accounting for 55.32%; and 412 strains belonged to subgenotype C2, accounting for 97.40%. The mean nucleotide homology of the VP1 region of CVA4 isolates compared with reference sequences was 93.81%, and the mean amino acid homology was 98.66%. nucleotide composition was adenine, cytosine, uracil, and guanine, accounting for 28.49%, 25.45%, 23.79%, and 22.27%, respectively. The three most abundant amino acids were threonine, alanine, and serine, accounting for 10.96%, 7.69%, and 7.62%, respectively. The nucleotide evolutionary rate of the VP1 region of subgenotype C2 strains was approximately 2.93×10-3 (95%CI: 2.86×10-3-2.99×10-3) substitutions per (site per year). Positions 200 and 274 of the VP1 region of CVA4 isolates were identified as high-frequency mutation sites, with entropy values of 0.61 and 0.69, respectively. The dominant substitutions were VP1-A200T and VP1-K274R. Conclusions CVA4 isolates were predominantly circulated in the southwestern region and belonged to subgenotype C2 from 1996 to 2024. The VP1 region presented distinct evolutionary features and high-frequency mutation sites.
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Received: 29 January 2026
Revised: 17 March 2026
Published: 22 June 2026
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