Key Laboratory of Zoonosis Research, Ministry of Education, Institute of Zoonosis, College of Veterinary Medicine, Jilin University, Changchun, Jilin, China.
Changchun Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Changchun, Jilin, China.
Vet Microbiol. 2022 Apr;267:109390. doi: 10.1016/j.vetmic.2022.109390. Epub 2022 Mar 2.
Influenza A virus (IAV) is one of the most dominant zoonotic-pathogen that causes annually recurring epidemic disease. The detailed molecular mechanism underlying IAV infection is still not fully understood. Circular RNAs (circRNAs) are generated from RNA back-splicing and involved in diverse biological processes. Here, we employed high-throughput circRNA microarray technology to profile circRNA expression in A549 cells in response to IAV infection. The analysis data revealed that 178 circRNAs expression were significantly upregulated while 137 downregulated, respectively, compared to the mock (P＜0.05, Fold Change＞2). Subsequently, Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were also conducted. Moreover dysregulated circRNAs were characterized, and of which nine were verified by quantitative real-time PCR (qRT-PCR). We further confirmed that circRNA_0082633 expression was increased following IAV infection. Overexpression of circRNA_0082633 suppressed IAV infection while depletion of circRNA_0082633 promoted viral proliferation. Interestingly, the activation of Janus kinase (JAK)-signal transducer and activator of transcription (STAT) signaling was involved in IAV-induced circ_0082633 expression. More importantly, we demonstrated that circ_0082633 expression enhanced type I interferon (IFN) signaling by IFN-stimulated response element (ISRE) promoter activity and Ifnb1 mRNA levels. These data firstly provided the expression profile of circRNAs in PR8-infected A549 cells and shed new light on the pathogenesis research of IAV infection. Our findings also suggest that circRNA_0082633 served an important function in IAV infection.
甲型流感病毒（IAV）是一种最主要的动物源性病原体，可导致每年反复发生的传染病。IAV 感染的详细分子机制尚不完全清楚。环状 RNA（circRNA）是由 RNA 反向剪接产生的，参与多种生物学过程。在这里，我们采用高通量 circRNA 微阵列技术分析 A549 细胞在 IAV 感染时的 circRNA 表达谱。分析数据显示，与对照相比，178 个 circRNA 的表达分别显著上调，而 137 个 circRNA 的表达下调（P＜0.05，倍数变化＞2）。随后，还进行了基因本体论（GO）和京都基因与基因组百科全书（KEGG）分析。此外，还对失调的 circRNA 进行了特征分析，其中 9 个通过定量实时 PCR（qRT-PCR）进行了验证。我们进一步证实，circRNA_0082633 的表达在 IAV 感染后增加。circRNA_0082633 的过表达抑制了 IAV 感染，而 circRNA_0082633 的缺失则促进了病毒的增殖。有趣的是，Janus 激酶（JAK）-信号转导和转录激活因子（STAT）信号的激活参与了 IAV 诱导的 circ_0082633 表达。更重要的是，我们证明了 circ_0082633 通过干扰素刺激反应元件（ISRE）启动子活性和 Ifnb1 mRNA 水平增强了 I 型干扰素（IFN）信号。这些数据首次提供了 PR8 感染的 A549 细胞中 circRNAs 的表达谱，并为 IAV 感染的发病机制研究提供了新的线索。我们的研究结果还表明，circRNA_0082633 在 IAV 感染中发挥了重要作用。
