Identification and characterization of circular RNAs in the A549 cells following Influenza A virus infection

Identification and characterization of circular RNAs in the A549 cells following Influenza A virus infection
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DOI:
10.1016/j.vetmic.2022.109390
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发表时间:
2022-03-12
影响因子:
3.3
通讯作者:
Duan, Ming
Duan, Ming
中科院分区:
农林科学2区
文献类型:
--
作者:
Guo, Yidi;Yu, Xiaohang;Duan, Ming

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甲型流感病毒(IAV)是最主要的人畜共患病病原体之一,每年引起反复流行的疾病。IAV感染的详细分子机制仍不完全清楚。环状RNA(CircRNAs)是由RNA反向剪接产生的,参与多种生物学过程。在这里,我们使用高通量CircRNA微阵列技术来分析A549细胞对IAV感染的CircRNA表达。分析数据显示,与模型组相比,178个CircRNA表达显著上调,137个CircRNA表达下调(P2)。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,还鉴定了异常的CircRNA,其中9个通过实时定量聚合酶链式反应(qRT-PCR)进行了验证。我们进一步证实了鸡传染性支气管炎病毒感染后CircRNA_0082633的表达增加。过表达CircRNA_0082633抑制病毒感染,而缺失CircRNA_0082633则促进病毒增殖。有趣的是,JAK信号转导和转录激活因子(STAT)信号通路的激活参与了IAV诱导的CIRC_0082633的表达。更重要的是,我们证明了CIRC_0082633的表达通过干扰素刺激的反应元件启动子活性和Ifnb1mRNA水平增强了I型干扰素信号。这些数据首次提供了在PR8感染的A549细胞中CircRNAs的表达谱,为研究IAV感染的发病机制提供了新的线索。我们的研究结果还表明,CircRNA_0082633在IAV感染中起着重要作用。
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 (P2). 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.