microRNA Function Is Limited to Cytokine Control in the Acute Response to Virus Infection.
microRNA Function Is Limited to Cytokine Control in the Acute Response to Virus Infection.
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DOI：
10.1016/j.chom.2015.11.003
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发表时间：
2015-12-09
影响因子：
30.3
通讯作者：
tenOever BR
中科院分区：
文献类型：
--
作者：
Aguado LC;Schmid S;Sachs D;Shim JV;Lim JK;tenOever BR
MicroRNAs(MiRNAs)具有通过序列特异性相互作用微调蛋白质表达的能力，有助于调节细胞的维持和分化。虽然一些研究也表明miRNAs是抗病毒反应的调节者，但另一些研究发现，促进miRNA介导的沉默的RISC复合体在细胞应激，包括病毒感染时无法发挥作用。为了确定miRNAs在细胞对病毒感染的反应中的全球作用，我们创造了一个载体，在终末分化的原代培养中快速消除总的细胞miRNA群体。MiRNAs的缺失对急性病毒感染的先天感知和即时反应的影响可以忽略不计。相反，miRNA耗尽特异性地增强细胞因子的表达，为细胞应激期间的免疫细胞激活提供了一种翻译后机制。这项工作强调了miRNAs在抗病毒反应中的生理作用，并表明它们的贡献仅限于慢性感染和适应性免疫反应的急性激活。
With the capacity to fine-tune protein expression via sequence-specific interactions, microRNAs (miRNAs) help regulate cell maintenance and differentiation. While some studies have also implicated miRNAs as regulators of the antiviral response, others have found that the RISC complex that facilitates miRNA-mediated silencing is rendered non-functional during cellular stress, including virus infection. To determine the global role of miRNAs in the cellular response to virus infection, we generated a vector that rapidly eliminates total cellular miRNA populations in terminally differentiated primary cultures. Loss of miRNAs has a negligible impact on both innate sensing of and immediate response to acute viral infection. In contrast, miRNA depletion specifically enhances cytokine expression, providing a post-translational mechanism for immune cell activation during cellular stress. This work highlights the physiological role of miRNAs during the antiviral response and suggests their contribution is limited to chronic infections and the acute activation of the adaptive immune response.