Orf is a zoonotic disease that has caused huge economic losses globally. Systematical analysis of dysregulated cellular micro RNAs (miRNAs) in response to Orf virus (ORFV) infection has not been reported. In the current study, miRNA sequencing and RNA sequencing (RNA-seq) were performed in goat skin fibroblast (GSF) cells at 0, 18, and 30 h post infection (h.p.i). We identified 140 and 221 differentially expressed (DE) miRNAs at 18 and 30 h.p.i, respectively. We also identified 729 and 3961 DE genes (DEGs) at 18 and 30 h.p.i, respectively. GO enrichment analysis indicates enrichment of apoptotic regulation, defense response to virus, immune response, and inflammatory response at both time points. DE miRNAs and DEGs with reverse expression were used to construct miRNA-gene networks. Seven DE miRNAs and seven DEGs related to "negative regulation of viral genome replication" were identified. These were validated by RT-qPCR. Cfa-let-7a, a significantly upregulated miRNA, was found to repress Thrombospondin 1 (THBS1) mRNA and protein expression by directly targeting the THBS1 3' untranslated region. THBS1 has been reported to induce apoptosis; therefore, the cfa-let-7a-THBS1 axis may play an important role in cellular apoptosis during ORFV infection. This study provides new insights into ORFV and host cell interaction mechanisms.

中文翻译：

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响应于Orf病毒感染的山羊皮肤成纤维细胞中差异表达的miRNA和mRNA的整合分析揭示了cfa-let-7a调节血小板反应蛋白1的表达。

Orf是一种人畜共患病，已在全球范围内造成巨大的经济损失。尚未对响应Orf病毒（ORFV）感染的细胞微RNA（miRNA）失调进行系统分析。在当前研究中，在感染后（hpi）的0、18和30小时，在山羊皮肤成纤维细胞（GSF）细胞中进行了miRNA测序和RNA测序（RNA-seq）。我们分别在18和30 hpi鉴定了140和221个差异表达（DE）miRNA。我们还分别在18和30 hpi鉴定了729和3961 DE基因（DEG）。GO富集分析表明，在两个时间点，凋亡调节，对病毒的防御反应，免疫反应和炎症反应均富集。具有反向表达的DE miRNA和DEG用于构建miRNA基因网络。与“有关”的七个DE miRNA和七个DEG cfa-let-7a-THBS1轴可能在ORFV感染期间的细胞凋亡中发挥重要作用。这项研究提供了对ORFV和宿主细胞相互作用机制的新见解。cfa-let-7a-THBS1轴可能在ORFV感染期间的细胞凋亡中发挥重要作用。这项研究提供了对ORFV和宿主细胞相互作用机制的新见解。