Cardif is an adaptor protein in the RIG-I antiviral pathway and is targeted by hepatitis C virus
Cardif is an adaptor protein in the RIG-I antiviral pathway and is targeted by hepatitis C virus
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DOI：
10.1038/nature04193
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发表时间：
2005-10-20
期刊：
影响因子：
64.8
通讯作者：
Tschopp, R
中科院分区：
文献类型：
--
作者：
Meylan, E;Curran, J;Tschopp, R
抗病毒对病原体的免疫力在被病毒相关的结构识别后安装。这些病毒的“特征”之一，双链（DS）RNA是感染细胞中大多数病毒的复制产物，并通过Toll-like受体3（TLR3）和最近鉴定的胞质RNA Helicass Ig-I（视际攻击性次要识别）感测。酸诱导的基因I，也称为DDX58）和MDA5（黑色素瘤分化相关基因5，也称为IFIH1或直升机）（1）。两种解旋酶都检测DSRNA及通过其蛋白质相互作用的卡域，中继不确定的信号，导致转录因子激活干扰素调节因子3（IRF3）和NF-kappaB。在这里，我们描述了cardif，我们描述了一个新的含卡的适配器与RIG-I相互作用和招募IKK Alpha，IKK Beta和IKK Epsilon激酶的蛋白质C末端区域，导致NF-KAPPA B和IRF3的激活。 CardIF的过表达导致干扰素-beta和NF-kappa B启动子激活，以及通过短干扰RNA抑制rig-i依赖性抗病毒反应的cardif。 CardIF是由NS3-4A靶向和灭活的，NS3-4A是丙型肝炎病毒的丝氨酸蛋白酶，已知可阻止干扰素β产生。 CardiF因此充当适配器，将细胞质DSRNA受体RIG-I与抗病毒程序的启动联系起来。
Antiviral immunity against a pathogen is mounted upon recognition by the host of virally associated structures. One of these viral 'signatures', double-stranded (ds) RNA, is a replication product of most viruses within infected cells and is sensed by Toll-like receptor 3 (TLR3) and the recently identified cytosolic RNA helicases RIG-I (retinoic acid inducible gene I, also known as Ddx58) and Mda5 (melanoma differentiation-associated gene 5, also known as Ifih1 or Helicard)(1). Both helicases detect dsRNA, and through their protein-interacting CARD domains, relay an undefined signal resulting in the activation of the transcription factors interferon regulatory factor 3 (IRF3) and NF-kappa B. Here we describe Cardif, a new CARD-containing adaptor protein that interacts with RIG-I and recruits IKK alpha, IKK beta and IKK epsilon kinases by means of its C-terminal region, leading to the activation of NF-kappa B and IRF3. Overexpression of Cardif results in interferon-beta and NF-kappa B promoter activation, and knockdown of Cardif by short interfering RNA inhibits RIG-I-dependent antiviral responses. Cardif is targeted and inactivated by NS3-4A, a serine protease from hepatitis C virus known to block interferon-beta production. Cardif thus functions as an adaptor, linking the cytoplasmic dsRNA receptor RIG-I to the initiation of antiviral programmes.