{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T05:59:21Z","timestamp":1792216761185,"version":"4.4.0"},"reference-count":37,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,12,16]],"date-time":"2025-12-16T00:00:00Z","timestamp":1765843200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell. Infect. Microbiol."],"abstract":"<jats:p>Enterovirus A71 (EV-A71) is one of the main pathogens causing hand, foot, and mouth disease (HFMD), and this virus exhibits substantial genetic diversity. To clarify its genomic evolutionary features, this study conducted a phylodynamic analysis on EV-A71 viruses collected in Qingdao (a northern Chinese city) between 2023 and 2024. EV-A71 was identified using a commercial real-time quantitative PCR (qPCR) assay; EV-A71-positive samples were then inoculated into rhabdomyosarcoma (RD) cells for virus isolation. The complete genome sequences and VP1 gene sequences of EV-A71 strains were amplified and analyzed, with IQ-TREE, SimPlot, and RDP4 software used to evaluate their evolutionary characteristics. Among 2,083 clinical samples, 27 were EV-A71-positive, with 19 isolates successfully cultured. Whole-genome analysis confirmed the co-circulation of EV-A71 genotypes C4 (5 strains) and B5 (14 strains). The C4 strains showed high homology to a strain isolated in China in 2019 and carried six lineage-specific mutations. In contrast, the B5 strains clustered into two distinct lineages, including recombinants that had undergone genetic recombination with coxsackievirus A4 (CV-A4) and coxsackievirus A2 (CV-A2). Notably, all EV-A71 strains collected from Qingdao maintained a serine (S) at the 17th amino acid residue of the VP1 region. This work enhances our understanding of the geographical distribution of EV-A71 by confirming the sustained circulation of genotype B5 in northern China and identifying a novel C4\/B5 co-circulation pattern in Qingdao\u2014a pattern reflecting complex local evolutionary dynamics. It emphasizes expanding genomic sequencing coverage to monitor B5 and recombinant strains, refining surveillance, and guiding HFMD prevention and control.<\/jats:p>","DOI":"10.3389\/fcimb.2025.1684067","type":"journal-article","created":{"date-parts":[[2025,12,16]],"date-time":"2025-12-16T06:28:22Z","timestamp":1765866502000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Genetic characterization of human enterovirus A71 genotypes C4 and B5 Circulating in Qingdao City, Shandong province, China, from 2023 to 2024"],"prefix":"10.3389","volume":"15","author":[{"given":"Jinling","family":"Gong","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sitong","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Song","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rui","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siying","family":"Xiao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhilei","family":"Su","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiuge","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyan","family":"Shi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xianming","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhaoguo","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,12,16]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"3192","DOI":"10.1128\/JCM.00628-08","article-title":"Molecular epidemiology of human enterovirus 71 in the United Kingdom from 1998 to 2006","volume":"46","author":"Bible","year":"2008","journal-title":"J. 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