The TAR-RNA binding protein is required for immunoresponses triggered by Cardiovirus infection.

The TAR-RNA binding protein is required for immunoresponses triggered by Cardiovirus infection.
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DOI:
10.1016/j.bbrc.2016.10.023
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发表时间:
2016-11-11
影响因子:
3.1
通讯作者:
Horvath CM
Horvath CM
中科院分区:
生物学4区
文献类型:
--
作者:
Komuro A;Homma Y;Negoro T;Barber GN;Horvath CM

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LGP 2和MDA 5合作检测小RNA病毒感染细胞的细胞质中的病毒RNA并激活先天免疫应答。为了进一步确定LGP 2/MDA 5识别RNA的调控组分,使用酵母双杂交筛选来鉴定LGP 2相互作用蛋白。筛选已经鉴定了TAR-RNA结合蛋白(TRBP),已知其是RNA干扰(RNAi)的重要因子。免疫沉淀实验表明,TRBP与LGP 2特异性相互作用,但不与相关的RIG-I样受体,RIG-I或MDA 5。siRNA敲低实验表明TRBP对于HBV触发的干扰素应答是重要的,但TRBP不参与仙台病毒触发的干扰素应答,其主要由RIG-I介导。为了支持与LGP 2的功能性相互作用,仅当LGP 2和MDA 5共表达而不是单独的MDA 5时,过表达的TRBP增加了HIV病毒触发的干扰素启动子活性。总之,我们的研究结果说明了RNAi调节因子和抗病毒RNA识别之间的可能联系,这是病毒诱导的先天免疫反应的分支特别需要的。
LGP2 and MDA5 cooperate to detect viral RNA in the cytoplasm of Picornavirus-infected cells and activate innate immune responses. To further define regulatory components of RNA recognition by LGP2/MDA5, a yeast two-hybrid screen was used to identify LGP2-interacting proteins. The screening has identified the TAR-RNA binding protein (TRBP), which is known to be an essential factor for RNA interference (RNAi). Immuno-precipitation experiments demonstrated that TRBP interacted specifically with LGP2 but not with related RIG-I-like receptors, RIG-I or MDA5. siRNA knockdown experiments indicate that TRBP is important for Cardiovirus-triggered interferon responses, but TRBP is not involved in Sendai virus-triggered interferon response that is mediated mainly by RIG-I. To support functional interaction with LGP2, overexpressed TRBP increased Cardiovirus-triggered interferon promoter activity only when LGP2 and MDA5 are co-expressed but not MDA5 alone. Together, our findings illustrate a possible connection between an RNAi-regulatory factor and antiviral RNA recognition that is specifically required for a branch of the virus induced innate immune response.
通过RIG-I介导的5'-二磷酸RNA识别的抗病毒药免疫。
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