RNA- and virus-independent inhibition of antiviral signaling by RNA helicase LGP2
RNA- and virus-independent inhibition of antiviral signaling by RNA helicase LGP2
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DOI：
10.1128/jvi.01325-06
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发表时间：
2006-12-01
影响因子：
5.4
通讯作者：
Horvath, Curt M.
中科院分区：
文献类型：
--
作者：
Komuro, Akihiko;Horvath, Curt M.
抗病毒先天免疫反应可以是由病毒感染引起的细胞内核酸的积累而触发的。双链RNA（DSRNA）可以通过细胞质RNA Helicase蛋白RIG-1和MDA5检测，这是两种在caspase募集结构域（Card）和DEXD/H Box RNA Helicase域中共享序列相似性的蛋白。这些蛋白被认为是DSRNA传感器，并被认为可以通过卡相互作用将信号传输到线粒体适配器IPS-1（也称为MAV，Visa或Cardif）。 IPS-1协调蛋白激酶的活性，该蛋白激酶激活诱导β-干扰素（IFN-β）基因转录所需的转录因子。另一种解旋酶蛋白LGP2缺乏卡区域，不会激活IFN-β基因表达。 LGP2 mRNA由干扰素，DSRNA处理或仙台病毒感染诱导，并充当抗病毒信号传导的反馈抑制剂。结果表明，LGP2可以通过与IPS-1一起参与蛋白质复合物，独立于DSRNA或病毒感染中间体抑制抗病毒信号传导。实验表明，LGP2可以与IPS-1上的共同相互作用位点与激酶IKKI（也称为IKK Epsilon）竞争。这些结果提供了蛋白质相互作用的首次证明，这是LGP2对细胞内抗病毒信号的负反馈调节的元素。
Antiviral innate immune responses can be triggered by accumulation of intracellular nucleic acids resulting from virus infections. Double-stranded RNA (dsRNA) can be detected by the cytoplasmic RNA helicase proteins RIG-1 and MDA5, two proteins that share sequence similarities within a caspase recruitment domain (CARD) and a DExD/H box RNA helicase domain. These proteins are considered dsRNA sensors and are thought to transmit the signal to the mitochondrial adapter, IPS-1 (also known as MAVS, VISA, or CARDIF) via CARD interactions. IPS-1 coordinates the activity of protein kinases that activate transcription factors needed to induce beta interferon (IFN-beta) gene transcription. Another helicase protein, LGP2, lacks the CARD region and does not activate IFN-beta gene expression. LGP2 mRNA is induced by interferon, dsRNA treatments, or Sendai virus infection and acts as a feedback inhibitor for antiviral signaling. Results indicate that LGP2 can inhibit antiviral signaling independently of dsRNA or virus infection intermediates by engaging in a protein complex with IPS-1. Experiments suggest that LGP2 can compete with the kinase IKKi (also known as IKK epsilon) for a common interaction site on IPS-1. These results provide the first demonstration of protein interaction as an element of negative-feedback regulation of intracellular antiviral signaling by LGP2.