肺源性外泌体 miR-483-3p 调控流感病毒感染的固有免疫反应。
Lung-Derived Exosomal miR-483-3p Regulates the Innate Immune Response to Influenza Virus Infection.
机构信息
Division of Virology, Department of Microbiology and Immunology, Japan.
Department of Special Pathogens, International Research Center for Infectious Diseases, Institute of Medical Science, University of Tokyo, Japan.
出版信息
J Infect Dis. 2018 Apr 11;217(9):1372-1382. doi: 10.1093/infdis/jiy035.
Exosomes regulate cell-cell communication by transferring functional proteins and RNAs between cells. Here, to clarify the function of exosomes during influenza virus infection, we characterized lung-derived exosomal microRNAs (miRNAs). Among the detected miRNAs, miR-483-3p was present at high levels in bronchoalveolar lavage fluid (BALF) exosomes during infection of mice with various strains of influenza virus, and miR-483-3p transfection potentiated gene expression of type I interferon and proinflammatory cytokine upon viral infection of MLE-12 cells. RNF5, a regulator of the RIG-I signaling pathway, was identified as a target gene of miR-483-3p. Moreover, we found that CD81, another miR-483-3p target, functions as a negative regulator of RIG-I signaling in MLE-12 cells. Taken together, this study indicates that BALF exosomal miRNAs may mediate the antiviral and inflammatory response to influenza virus infection.
外泌体通过在细胞间转移功能性蛋白质和 RNA 来调节细胞间通讯。在这里，为了阐明外泌体在流感病毒感染过程中的功能，我们对肺来源的外泌体 microRNAs（miRNAs）进行了特征分析。在检测到的 miRNAs 中，miR-483-3p 在感染各种流感病毒的小鼠的支气管肺泡灌洗液（BALF）外泌体中含量较高，并且 miR-483-3p 转染可增强 MLE-12 细胞感染病毒时Ⅰ型干扰素和促炎细胞因子的基因表达。RIG-I 信号通路的调节因子 RNF5 被鉴定为 miR-483-3p 的靶基因。此外，我们发现 CD81 是 miR-483-3p 的另一个靶基因，它在 MLE-12 细胞中作为 RIG-I 信号的负调节剂发挥作用。综上所述，本研究表明 BALF 外泌体 miRNAs 可能介导了对流感病毒感染的抗病毒和炎症反应。
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