Biology Program, New York University Abu Dhabi (NYUAD), Abu Dhabi, United Arab Emirates.
Institute of Cellular and System Medicine, National Health Research Institutes, Zhunan, Taiwan.
Front Immunol. 2019 Apr 17;10:836. doi: 10.3389/fimmu.2019.00836. eCollection 2019.
The activation of innate immunity by viral nucleic acids present in the cytoplasm plays an essential role in controlling viral infection in both immune and non-immune cells. The dsDNA and dsRNA viral mimics can stimulate the cytosolic nucleic acids sensors and activate the antiviral innate immunity. In this study, taking advantage of dsDNA and dsRNA viral mimics, we investigated the global transcriptome changes after the antiviral immunity activation in mouse embryonic fibroblasts. Results from our data identified a positive feedback up-regulation of sensors (e.g., ), transducers (e.g., ) and transcription factors (e.g., ) in multiple pathways involved in detecting viral or microbial infections upon viral mimic stimulation. A group of genes involved in DNA damage response and DNA repair such as were also up-regulated, implying the involvement of these genes in antiviral immunity. Molecular function analysis further showed that groups of helicase genes (e.g., ), nuclease genes (e.g., ), methyltransferase genes (e.g., histone methyltransferase ; RNA methyltransferase ), and protein ubiquitin-ligase genes (e.g., genes and genes) were up-regulated upon antiviral immunity activation. In contrast, viral mimic stimulation down-regulated genes involved in a broad range of general biological processes (e.g., cell division, metabolism), cellular components (e.g., mitochondria and ribosome), and molecular functions (e.g., cell-cell adhesion, microtubule binding). In summary, our study provides valuable information about the global transcriptome changes upon antiviral immunity activation. The identification of novel groups of genes up-regulated upon antiviral immunity activation serves as useful resource for mining new antiviral sensors and effectors.
细胞质中存在的病毒核酸激活先天免疫，在免疫和非免疫细胞中控制病毒感染中发挥重要作用。dsDNA 和 dsRNA 病毒模拟物可以刺激细胞质核酸传感器并激活抗病毒先天免疫。在这项研究中，我们利用 dsDNA 和 dsRNA 病毒模拟物，研究了抗病毒免疫激活后小鼠胚胎成纤维细胞中的全转录组变化。我们的数据结果确定了在病毒模拟物刺激后，多个涉及检测病毒或微生物感染的途径中的传感器（例如 ）、转导器（例如 ）和转录因子（例如 ）的正向反馈上调。一组涉及 DNA 损伤反应和 DNA 修复的基因（例如 ）也被上调，表明这些基因参与抗病毒免疫。分子功能分析进一步表明，一组解旋酶基因（例如 ）、核酸酶基因（例如 ）、甲基转移酶基因（例如组蛋白甲基转移酶；RNA 甲基转移酶）和蛋白泛素连接酶基因（例如 基因和 基因）在抗病毒免疫激活时被上调。相反，病毒模拟物刺激下调了广泛涉及一般生物过程（例如细胞分裂、代谢）、细胞成分（例如线粒体和核糖体）和分子功能（例如细胞-细胞粘附、微管结合）的基因。总之，我们的研究提供了关于抗病毒免疫激活时全转录组变化的有价值信息。鉴定出的抗病毒免疫激活时上调的新基因群，为挖掘新的抗病毒传感器和效应子提供了有用的资源。
