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一种人类长非编码 RNA LncATV 通过限制 RIG-I 介导的固有免疫促进病毒复制。

A Human Long Non-coding RNA LncATV Promotes Virus Replication Through Restricting RIG-I-Mediated Innate Immunity.

机构信息

NHC Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

出版信息

Front Immunol. 2019 Jul 19;10:1711. doi: 10.3389/fimmu.2019.01711. eCollection 2019.

Abstract

Pattern recognition receptors sense pathogen components and initiate the host antiviral innate immune response, such as inducing interferons (IFNs). Long non-coding RNAs (lncRNAs) are emerging regulators of multiple biological processes. However, their role in antiviral response, especially through regulating the human innate immune, is largely unexplored. Here we characterized that lncATV, a human specific lncRNA, was up-regulated upon type I/III IFN stimulations and virus infection. LncATV was cytoplasmic localized and relatively high expressed in human monocytes, erythroleukemia cells and hepatoma cells. Notably, lncATV knockdown significantly inhibited the replication of multiple RNA viruses, such as hepatitis C virus, Zika virus, Newcastle disease virus, and Sendai virus. Mechanistically, RIG-I antiviral signaling and IFN effective pathway were enhanced when lncATV expression was knocked down but inhibited by overexpressed lncATV. RNA immunoprecipitation results demonstrated an association between LncATV and RIG-I. Collectively, our findings reveal the functional role of a novel human specific lncATV as a regulatory lncRNA restricting virus associated innate immune response.

摘要

模式识别受体感知病原体成分并启动宿主抗病毒先天免疫反应,例如诱导干扰素 (IFNs)。长链非编码 RNA (lncRNA) 是多种生物学过程的新兴调节因子。然而,它们在抗病毒反应中的作用,特别是通过调节人类先天免疫,在很大程度上仍未被探索。在这里,我们描述了 lncATV,一种人类特异性 lncRNA,在 I/III 型 IFN 刺激和病毒感染时上调。lncATV 定位于细胞质,在人单核细胞、红白血病细胞和肝癌细胞中相对高表达。值得注意的是,lncATV 敲低显著抑制多种 RNA 病毒的复制,如丙型肝炎病毒、寨卡病毒、新城疫病毒和仙台病毒。机制上,当 lncATV 表达被敲低时,RIG-I 抗病毒信号和 IFN 有效途径增强,但被过表达的 lncATV 抑制。RNA 免疫沉淀结果表明 LncATV 与 RIG-I 之间存在关联。总之,我们的研究结果揭示了一种新型人类特异性 lncATV 作为一种调节 lncRNA 限制病毒相关先天免疫反应的功能作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3471/6658999/36d499b4cec1/fimmu-10-01711-g0001.jpg

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