Department of Molecular Biosciences, Northwestern University, Evanston, Illinois, United States of America.
PLoS One. 2013 Sep 26;8(9):e76560. doi: 10.1371/journal.pone.0076560. eCollection 2013.
The mammalian antiviral response relies on the alteration of cellular gene expression, to induce the production of antiviral effectors and regulate their activities. Recent research has indicated that virus infections can induce the accumulation of cellular microRNA (miRNA) species that influence the stability of host mRNAs and their protein products. To determine the potential for miRNA regulation of cellular responses to influenza A virus infection, small RNA profiling was carried out using next generation sequencing. Comparison of miRNA expression profiles in uninfected human A549 cells to cells infected with influenza A virus strains A/Udorn/72 and A/WSN/33, revealed virus-induced changes in miRNA abundance. Gene expression analysis identified mRNA targets for a cohort of highly inducible miRNAs linked to diverse cellular functions. Experiments demonstrate that the histone deacetylase, HDAC1, can be regulated by influenza-inducible miR-449b, resulting in altered mRNA and protein levels. Expression of miR-449b enhances virus and poly(I:C) activation of the IFNβ promoter, a process known to be negatively regulated by HDAC1. These findings demonstrate miRNA induction by influenza A virus infection and elucidate an example of miRNA control of antiviral gene expression in human cells, defining a role for miR-449b in regulation of HDAC1 and antiviral cytokine signaling.
哺乳动物的抗病毒反应依赖于细胞基因表达的改变，以诱导抗病毒效应物的产生并调节它们的活性。最近的研究表明，病毒感染可以诱导细胞 microRNA（miRNA）物种的积累，这些 miRNA 影响宿主 mRNA 的稳定性及其蛋白质产物。为了确定 miRNA 调节细胞对甲型流感病毒感染反应的潜力，使用下一代测序进行了小 RNA 分析。将未感染的人 A549 细胞与感染甲型流感病毒株 A/Udorn/72 和 A/WSN/33 的细胞的 miRNA 表达谱进行比较，揭示了 miRNA 丰度的病毒诱导变化。基因表达分析确定了与多种细胞功能相关的高度诱导 miRNA 的 mRNA 靶标。实验表明，组蛋白去乙酰化酶 HDAC1 可以被流感诱导的 miR-449b 调节，导致 mRNA 和蛋白质水平的改变。miR-449b 的表达增强了病毒和 poly(I:C)对 IFNβ 启动子的激活，该过程已知受 HDAC1 的负调控。这些发现表明甲型流感病毒感染可诱导 miRNA 的产生，并阐明了 miRNA 控制人类细胞中抗病毒基因表达的一个例子，确定了 miR-449b 在调节 HDAC1 和抗病毒细胞因子信号转导中的作用。
