Cardif is an adaptor protein in the RIG-I antiviral pathway and is targeted by hepatitis C virus
Open accessAbstract
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). 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-kappaB. Here we describe Cardif, a new CARD-containing adaptor protein that interacts with RIG-I and recruits IKKalpha, IKKbeta and IKKvarepsilon kinases by means of its C-terminal region, leading to the activation of NF-kappaB and IRF3. Overexpression of Cardif results in interferon-beta and NF-kappaB 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.
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MAVS localization to the outer mitochondrial membrane is indispensable for its function in RLR signaling.
“A breakthrough in establishing the role for mitochondria in RLR-activated antiviral immunity was the identification of the RLR mitochondrial adaptor protein MAVS (mitochondrial antiviral-signaling protein)(Kawai et al., 2005; Meylan et al., 2005; Seth et al., 2005; Xu et al., 2005) localization to the outer mitochondrial membrane is indispensable for its function.”
From Mitochondria in the Regulation of Innate and Adaptive Immunity (2015) · cites this paper as Meylan et al., 2005
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- Authors
- Meylan, E., Curran, J., Hofmann, K., Moradpour, D., Binder, M., Bartenschlager, R., & Tschopp, J.
- Affiliations
- University of Lausanne (CH)
- University of Geneva (CH)
- Miltenyi Biotec (Germany) (DE)
- Centre Hospitalier Universitaire Vaudois (CH)
- Heidelberg University (DE)
- Corresponding author
- Tschopp, Jürg
- Venue
- Nature
- Published
- 2005-09-21
- Volume
- 437
- Issue
- 7062
- Pages
- 1167-1172
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W2093579074
- Cited by
- 2,401
- References
- 31
- Citations by year
- 2026: 37 · 2025: 59 · 2024: 52 · 2023: 72 · 2022: 68 · 2021: 109 · 2020: 99 · 2019: 101 · 2018: 91 · 2017: 110 · 2016: 102 · 2015: 121 · 2014: 160 · 2013: 167 · 2012: 144
- FWCI
- 49.42
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Dépôt institutionnel de l'Université libre de Bruxelles (Université Libre de Bruxelles) (submittedVersion, other-oa)
- Infoscience (Ecole Polytechnique Fédérale de Lausanne) (submittedVersion)
- Infoscience (Ecole Polytechnique Fédérale de Lausanne) (submittedVersion, cc-by-nc-nd)
- IRIS (submittedVersion)
- SERVAL (Université de Lausanne) (submittedVersion)
- Funders
- National Science Foundation
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › interferon and immune responses
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA regulation and disease
- Keywords
- Cardif, RIG-I, MDA5, hepatitis C virus, double-stranded RNA sensing, antiviral innate immunity, NF-κB activation, IRF3, interferon-beta, TLR3
- MeSH terms
- DEAD Box Protein 58, Viral Proteases, Amino Acid Sequence, Animals, Cell Line, DNA-Binding Proteins, Humans, Molecular Sequence Data, Protein Binding, Receptors, Immunologic, Serine Endopeptidases, Substrate Specificity, Transcription Factors, Hepacivirus, NF-kappa B, Interferon-beta, Protein Serine-Threonine Kinases, Viral Nonstructural Proteins, Protein Structure, Tertiary, RNA Helicases, Nucleoside-Triphosphatase, Adaptor Proteins, Signal Transducing, Interferon Regulatory Factor-3, Mice, I-kappa B Kinase, DEAD-box RNA Helicases
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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