Enterovirus A71 (EV-A71) is an important emerging virus posing a threat to children under five years old. Circular RNAs (circRNAs), a novel class of endogenous RNAs, have been recognized to play important roles in the onset and development of viral diseases. However, it has not been determined which specific circRNAs are involved in the pathological mechanisms of EV-A71 infection. In this study, RNA-sequencing (RNA-seq) was conducted to characterize differentially expressed circRNAs during the process of EV-A71 infection. Overall, 8726, 10405 and 4710 circRNAs were detected in the control, EV-A71-12 h and EV-A71-24 h groups, respectively, of which 1851 and 951 circRNAs were differentially expressed in the EV-A71-12 h and EV-A71-24 h groups versus the control group. The overlapping circRNAs in the EV-A71-infected groups were subjected to Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, which further demonstrated that the host genes of these circRNAs were principally implicated in activities associated with the progression of viral infection, such as immune system process, Wnt signaling pathway, etc. Additionally, qRT-PCR detection showed that six selected circRNAs were identical to the sequencing data. To excavate the key circRNAs in EV-A71 infection, we comprehensively evaluated and integrated the relationship of circRNA/miRNA/mRNA, and eventually screened 2 key circRNA regulatory axes, namely hsa_circ_0017115/hsa-miR-150-5p/EGR1 and hsa_circ_0005060/hsa-miR-4685-5p/MMP2. In summary, our findings not only provide the first comprehensive expression and functional profile of circRNAs in response to EV-A71 infection, but also offer a novel direction to elucidate the molecular mechanism underlying viral pathogenesis and the cellular immune response in host-EV-A71 interactions.

肠道病毒 A71 (EV-A71) 是一种重要的新兴病毒，对五岁以下儿童构成威胁。环状 RNA (circRNA) 是一类新型的内源性 RNA，已被认为在病毒性疾病的发生和发展中发挥重要作用。然而，尚未确定哪些特定的 circRNA 参与了 EV-A71 感染的病理机制。在这项研究中，进行了 RNA 测序 (RNA-seq) 以表征 EV-A71 感染过程中差异表达的 circRNA。总体而言，在对照组、EV-A71-12 h 和 EV-A71-24 h 组中分别检测到 8726、10405 和 4710 个 circRNA，其中 1851 和 951 个 circRNA 在 EV-A71-12 h 和 EV 中差异表达-A71-24 小时组与对照组。对 EV-A71 感染组中重叠的 circRNA 进行基因本体论 (GO) 和京都基因和基因组百科全书 (KEGG) 富集分析，进一步证明这些 circRNA 的宿主基因主要参与与病毒感染的进展，如免疫系统过程、Wnt 信号通路等。此外，qRT-PCR 检测显示，6 个选定的 circRNA 与测序数据相同。为挖掘EV-A71感染的关键circRNA，我们综合评价和整合circRNA/miRNA/mRNA的关系，最终筛选出2个关键的circRNA调控轴，即hsa_circ_0017115/hsa-miR-150-5p/EGR1和hsa_circ_0005060/hsa -miR-4685-5p/MMP2。总之，