MiR-221 negatively regulates innate anti-viral response.

MiR-221 negatively regulates innate anti-viral response.
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MiR-221 负向调节先天抗病毒反应

DOI:
10.1371/journal.pone.0200385
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发表时间:
2018
期刊:
影响因子:
3.7
通讯作者:
You F
You F
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Du H;Cui S;Li Y;Yang G;Wang P;Fikrig E;You F

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先天免疫系统在最初的抗病毒反应中发挥着关键作用。然而,在感染期间必须严格调节这些反应的时间和持续时间,以确保适当的免疫细胞激活和抗病毒防御。在这里,我们证明在抗病毒反应期间,负调节因子 miR-221 也以 ELF4 依赖性方式被诱导。我们进一步表明 ELF4 通过直接结合 miR-221 的启动子来促进 miR-221 的表达。过表达和敲低实验表明,miR-221 可以在病毒感染时负向调节 IFNβ 的产生。对 miR-221 过表达细胞的 RNA-seq 分析揭示了多个候选靶标。综上所述,我们的研究发现了一种新型的先天抗病毒反应的负 microRNA 调节因子,它依赖于 ELF4。
The innate immune system plays a critical role in the initial antiviral response. However, the timing and duration of these responses must be tightly regulated during infection to ensure appropriate immune cell activation and anti-viral defenses. Here we demonstrate that during antiviral response, a negative regulator miR-221 was also induced in an ELF4-dependent manner. We further show that ELF4 promotes miR-221 expression through direct binding to its promoter. Overexpression and knockdown assay show that miR-221 can negatively regulate IFNβ production in time of virus infection. RNA-seq analysis of miR-221 overexpressed cells revealed multiple candidate targets. Taken together, our study identified a novel negative microRNA regulator of innate antiviral response, which is dependent on ELF4.
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