CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China.
Savaid Medical School, University of Chinese Academy of Sciences, Beijing 100039, China.
Int J Mol Sci. 2022 Aug 31;23(17):9901. doi: 10.3390/ijms23179901.
Circular RNAs (circRNAs) are involved in diverse biological processes. Avian influenza virus (AIV) can cross the species barrier to infect humans. Here, we employed RNA sequencing technology to profile circRNA, microRNA, and mRNA expression in human lung carcinoma cells in response to AIV or human influenza A virus (IAV) infection at viral replication. The analysis revealed that the expression of 475 common circRNAs were significantly regulated. The 381 and 1163 up-regulated circRNAs were induced by AIV at 8 and 16 h, respectively. Subsequently, gene ontology and Kyoto Encyclopedia of Genes and Genomes analyses were also conducted for the AIV-specific up-regulated circRNAs. Moreover, the circRNAs were characterized, of which six were verified by quantitative real-time PCR. We further confirmed that expression of the selected circRNAs only increased following AIV infection. Knocking down the selected circRNAs promoted AIV proliferation, and overexpression of three of the candidate circRNAs restricted AIV replication and proliferation. We further analyzed that AIV-specific up-regulated circRNA mechanisms might function through the ceRNA network to affect the "Endocytosis" pathway and the "Cell cycle process". These data provide the first expression profile of AIV-specific up-regulated circRNAs and shed new light on the pathogenesis of AIV infection. Our findings also suggest that these circRNAs serve an important role in AIV infection.
环状 RNA（circRNA）参与多种生物学过程。禽流感病毒（AIV）可以跨越物种屏障感染人类。在这里，我们采用 RNA 测序技术在病毒复制时研究了人肺癌细胞对 AIV 或人流感 A 病毒（IAV）感染的 circRNA、microRNA 和 mRNA 表达谱。分析表明，475 个常见 circRNA 的表达受到显著调控。AIV 在 8 小时和 16 小时分别诱导了 381 个和 1163 个上调的 circRNA。随后，还对 AIV 特异性上调的 circRNAs 进行了基因本体和京都基因与基因组百科全书分析。此外，还对 circRNAs 进行了特征分析，其中 6 个通过定量实时 PCR 进行了验证。我们进一步证实，只有在 AIV 感染后，这些选定的 circRNAs 的表达才会增加。敲低选定的 circRNAs 促进了 AIV 的增殖，而候选 circRNAs 中的三个的过表达限制了 AIV 的复制和增殖。我们进一步分析表明，AIV 特异性上调的 circRNA 机制可能通过 ceRNA 网络发挥作用，影响“内吞作用”途径和“细胞周期过程”。这些数据提供了 AIV 特异性上调的 circRNAs 的第一个表达谱，并为 AIV 感染的发病机制提供了新的见解。我们的研究结果还表明，这些 circRNAs 在 AIV 感染中发挥着重要作用。
