Integrated analysis of microRNA-mRNA expression in A549 cells infected with influenza A viruses (IAVs) from different host species
Integrated analysis of microRNA-mRNA expression in A549 cells infected with influenza A viruses (IAVs) from different host species
复制标题
不同宿主物种甲型流感病毒（IAV）感染的 A549 细胞中 microRNA-mRNA 表达的综合分析
DOI：
10.1016/j.virusres.2018.12.016
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发表时间：
2019-04-02
期刊：
影响因子：
5
通讯作者：
Fan, Xiaohui
中科院分区：
文献类型：
--
作者：
Gao, Jie;Gao, Lingxi;Fan, Xiaohui
尽管已经证明了几种miRNA参与流感病毒复制周期，但对感染来自不同宿主物种的甲型流感病毒（IAV）的A549细胞中表达的miRNA和mRNA的鉴定仍然研究不足。为了研究与A型流感病毒感染期间miRNA差异表达相关的分子机制，我们在感染人源季节性A型流感病毒H3 N2（Human_Br07）、猪源A型流感病毒H1N1（SW_3861）或禽源A型流感病毒H3 N2（AVI_9990）的A549细胞中进行了总体miRNA和mRNA表达谱分析。分别通过微阵列和高通量测序分析获得miRNA和mRNA表达谱。利用生物信息学工具对差异表达的miRNAs（DEMs）和差异表达的基因（DEGs）进行综合分析，并通过实时定量聚合酶链反应（RT-qPCR）验证miRNAs和mRNAs的表达。我们鉴定了20种miRNAs（6种上调和14种下调）和1286种mRNAs（935种上调和351种下调），与未感染的对照组相比，在三组感染的细胞中表现出相同的差异表达趋势。对这些表达谱的综合分析确定了79个与甲型流感参考途径相关的miRNA-mRNA对，107个与病毒防御相关的miRNA-mRNA相互作用。此外，所获得的结果得到了8个差异表达的miRNAs的RT-qPCR分析的支持。（hsa-miR-210- 3 p、hsa-miR-296- 5 p、hsa-miR-371 a-5 p、hsa-miR-762、hsa-miR-937- 5 p、hsa-miR-1915- 3 p、hsa-miR-3665和hsa-miR-1290）和13种差异表达的mRNA（IFNL1、CXCL10、RSAD 2、MX1、OAS 2、IFIT 2、1E144 L、MX2、XAF 1、NDRG 1、FGA、EGLN 3和TFRC）。我们的研究结果表明，失调的miRNA表达起着至关重要的作用，引起感染的IAV起源于不同的物种，并提供了基础，为进一步研究参与甲型流感病毒感染的miRNA的分子调控机制。
Although several miRNAs have been demonstrated to be involved in the influenza virus replication cycle, the identification of miRNAs and mRNAs that are expressed in A549 cells infected with influenza A viruses (IAVs) from different host species has remained poorly studied. To investigate the molecular mechanisms associated with the differential expression of miRNAs during influenza A virus infection, we performed global miRNA and mRNA expression profiling in A549 cells infected with human-origin seasonal influenza A virus H3N2 (Human_Br07), swine-origin influenza A virus H1N1 (SW_3861) or avian-origin influenza A virus H3N2 (AVI_9990). The miRNA and mRNA expression profiles were obtained by microarray and high-throughput sequencing analyses, respectively. The integrated analysis of differentially expressed miRNAs (DEMs) and differentially expressed genes (DEGs) was performed using bioinformatics tools, and the expression of miRNAs and mRNAs was validated by real-time quantitative polymerase chain reaction (RT-qPCR). We identified 20 miRNAs (6 upregulated and 14 downregulated) and 1286 mRNAs (935 upregulated and 351 downregulated) exhibiting the same differential expression trends in three infected groups of cells compared with an uninfected control. An integrated analysis of these expression profiles identified 79 miRNA-mRNA pairs associated with the influenza A reference pathway, and 107 miRNA-mRNA interactions were correlated with the defense of the virus. Additionally, the obtained results were supported by an RT-qPCR analysis of 8 differentially expressed miRNAs (hsa-miR-210-3p, hsa-miR-296-5p, hsa-miR-371a-5p, hsa-miR-762, hsa-miR-937-5p, hsa-miR-1915-3p, hsa-miR-3665, and hsa-miR-1290) and 13 differentially expressed mRNAs (IFNL1, CXCL10, RSAD2, MX1, OAS2, IFIT2, 1E144 L, MX2, XAF1, NDRG1, FGA, EGLN3, and TFRC). Our findings indicate that dysregulated miRNA expression plays a crucial role in infection caused by IAVs originating from different species and provide a foundation for further investigations of the molecular regulatory mechanisms of miRNAs involved in influenza A virus infection.