Cardif is an adaptor protein in the RIG-I antiviral pathway and is targeted by hepatitis C virus

Article

关键词: NF-KAPPA-B;    DOUBLE-STRANDED-RNA;    INTERFERON REGULATORY FACTOR-3;    MEMBRANE ASSOCIATION;    IKK-EPSILON;    ACTIVATION;    HELICASE;    IDENTIFICATION;    CLEAVAGE;    DETERMINANTS;   

DOI  :  10.1038/nature04193

来源: SCIE

【 摘 要 】

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.

【 授权许可】

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