Coxsackievirus A16 (CV-A16) has caused worldwide epidemics of hand, foot, and mouth disease (HFMD) in infants and preschool children. Circular RNAs (circRNAs), a class of noncoding RNA molecules, participate in the progression of viral infectious diseases. Although the function of circRNAs has been a heavily researched topic, their role in CV-A16 infection is still unclear. In this study, the viral effects of CV-A16 on the cellular circRNA transcriptome were investigated using next-generation sequencing technology. The results showed that a total of 8726, 8611, and 6826 circRNAs were identified at 0, 12, and 24 h postinfection, respectively. Moreover, it was found that 1769 and 1192 circRNAs were differentially expressed in at 12 and 24 h postinfection, respectively. The common differentially expressed circRNAs were used for functional annotation analysis, and it was found that the parent genes of differentially expressed circRNAs might be associated with the viral infection process, especially the “Immune system process” in GO analysis and the “Inflammation mediated by chemokine and cytokine signaling pathway” in KEGG analysis. Subsequently, circRNA-miRNA-mRNA regulatory networks were constructed, and the hsa_circ_0004447/hsa-miR-942-5p/MMP2, hsa_circ_0078617/hsa-miR-6780b-5p/MMP2 and hsa_circ_0078617/hsa-miR-5196-5p/MMP2 regulatory axes were identified by enrichment analysis as important networks during the progression of CV-A16 infection. Finally, six dysregulated circRNAs were selected for validation and were verified to be consistent with the sequencing results. Considering all of these results, to the best of our knowledge, this study is the first to present a comprehensive overview of circRNAs induced by CV-A16 infection, and this research demonstrated that a network of enriched circRNAs and circRNA-associated competitive endogenous RNAs (ceRNAs) is involved in the regulation of CV-A16 infection, thereby helping to elucidate the mechanisms underlying CV-A16-host interactions.

柯萨奇病毒 A16 (CV-A16) 已在全球范围内引起婴儿和学龄前儿童手足口病 (HFMD) 的流行。环状RNA（circRNAs）是一类非编码RNA分子，参与病毒感染性疾病的进程。尽管 circRNAs 的功能一直是一个深入研究的话题，但它们在 CV-A16 感染中的作用仍不清楚。在这项研究中，使用下一代测序技术研究了 CV-A16 对细胞 circRNA 转录组的病毒影响。结果表明，在感染后0、12和24小时分别鉴定出8726、8611和6826个circRNA。此外，发现在感染后 12 小时和 24 小时分别有 1769 和 1192 个 circRNA 差异表达。对常见的差异表达circRNAs进行功能注释分析，发现差异表达circRNAs的亲本基因可能与病毒感染过程有关，尤其是GO分析中的“免疫系统过程”和“趋化因子介导的炎症”。和细胞因子信号通路”在 KEGG 分析中。随后，构建了circRNA-miRNA-mRNA调控网络，hsa_circ_0004447/hsa-miR-942-5p/MMP2、hsa_circ_0078617/hsa-miR-6780b-5p/MMP2和hsa_circ_0078617/hsa-miR-5196-5p/MMP2调控通过富集分析将轴确定为 CV-A16 感染进展过程中的重要网络。最后，选择了 6 个失调的 circRNA 进行验证，并验证与测序结果一致。考虑到所有这些结果，