microRNA-136调控流感病毒复制的分子机制研究

MicroRNA (miRNA) is a kind of small non-coding RNA that can regulate posttranscriptional gene expression. More and more studies show that the miRNA is closely related to virus infection. The miRNA microarray was used on A549 cells infected by H9N2 avian influenza virus to screen the differentially expression miRNAs and the miR-136 was targeted. It was also found that miR-136 could inhibit the influenza virus replication in the cell significantly. The further study revealed that the miRNA-136 targeted the 3’ UTR region of IL-6, and also activated the strong innate immune response. However, the molecular mechanism on regulation of influenza virus replication by miR-136 is still not clear. This study intends to probe into the regulation of miRNA-136 expression by influenza virus, the feedback inhibition on the influenza virus by miRNA-136, the molecular structure characteristics of miR-136 and its relationship with innate immune pattern recognition receptor, in order to discover the molecular mechanism of miR-136 regulating IL - 6 expression and the molecular structural basis of innate immunity regulation, and point out the target molecule under miR-136 effect, eventually clarify the molecular mechanism of the miRNA-136 regulation of influenza virus infection, which should provide a the theoretical foundation for the development of new anti-influenza virus drugs.

microRNA（miRNA）是一类可介导转录后基因表达调控的小分子非编码RNA，越来越多的研究表明，miRNA与病毒感染密切相关。本项目利用miRNA芯片从H9N2禽流感病毒感染的人宿主细胞中筛选到差异表达的miR-136，发现其能显著抑制流感病毒在细胞上的复制，进一步研究发现miRNA-136能靶向IL-6的3’UTR区，并能激活很强的天然免疫反应，但是其调控流感病毒复制的分子机制仍不清楚。本项目拟通过深入研究流感病毒感染对miRNA-136表达的调控及miRNA-136对流感病毒的反馈抑制作用、miR-136的分子结构特点及其与天然免疫模式识别受体分子的关系等，揭示miR-136调控IL-6表达的分子机制及调控天然免疫的分子结构基础，并明确miR-136作用的靶分子，最终阐明miRNA-136在流感病毒感染过程中发挥调控作用的分子机制，为开发新型抗流感病毒药物提供理论基础。

microRNA（miRNA）是一类可介导转录后基因表达调控的小分子非编码RNA，越来越多的研究表明，miRNA与病毒感染密切相关。本项目利用miRNA芯片从禽流感病毒感染的人宿主细胞中筛选到差异表达的miR-136，发现其能显著抑制流感病毒在细胞上的复制，进一步研究发现miRNA-136能靶向IL-6的3’UTR区，并能激活很强的天然免疫反应，但是其调控流感病毒复制的分子机制仍不清楚。通过项目的实施，已完成了项目设定的研究目标。本研究阐明了流感病毒对宿主miRNA-136的调控作用，并鉴定miR-136是一个非常有效的抗病毒因子；确定miR-136是IL-6的负调控因子，在病毒感染过程中，miR-136可抑制由病毒诱发的IL-6过量表达；发现miR-136可作为细胞重要免疫蛋白RIG-I分子的配体激活剂，诱导强烈的天然免疫反应，也从分子水平证明miR-136与RIG-I蛋白存在相互作用关系，揭示了miR-136调控天然免疫的分子结构基础；并以小鼠为实验模型证明miR-136在动物体内水平能够抑制流感病毒在体内复制；从整体上解释miR-136，天然免疫和病毒三者之间的关系。通过本研究最终阐明miR-136参与调控细胞天然免疫和抑制流感病毒增殖的分子机制。为更深入理解流感病毒与宿主相互作用的关系提供理论基础，也将为抗流感病毒药物的研发提供新的思路。