The RNA helicase RIG-I has an essential function in double-stranded RNA-induced innate antiviral responses

  title={The RNA helicase RIG-I has an essential function in double-stranded RNA-induced innate antiviral responses},
  author={Mitsutoshi Yoneyama and Mika Kikuchi and Takashi Natsukawa and Noriaki Shinobu and Tadaatsu Imaizumi and Makoto Miyagishi and Kazunari Taira and Shizuo Akira and Takashi Fujita},
  journal={Nature Immunology},
Intracellular double-stranded RNA (dsRNA) is a chief sign of replication for many viruses. Host mechanisms detect the dsRNA and initiate antiviral responses. In this report, we identify retinoic acid inducible gene I (RIG-I), which encodes a DExD/H box RNA helicase that contains a caspase recruitment domain, as an essential regulator for dsRNA-induced signaling, as assessed by functional screening and assays. A helicase domain with intact ATPase activity was responsible for the dsRNA-mediated… 

RNA- and Virus-Independent Inhibition of Antiviral Signaling by RNA Helicase LGP2

Results indicate that LGP2 can inhibit antiviral signaling independently of dsRNA or virus infection intermediates by engaging in a protein complex with IPS-1, and provide the first demonstration of protein interaction as an element of negative-feedback regulation of intracellular antiviral signaled by L GP2.

[Virus-induced expression of type I interferon genes].

The function of RIG-I in antiviral innate immunity is discussed, which encodes a DExD/H box RNA helicase containing the caspase recruitment domain (CARD) as a critical regulator for dsRNA-induced signaling.

RIG-I-Mediated Antiviral Responses to Single-Stranded RNA Bearing 5'-Phosphates

It is shown that influenza A virus infection does not generate dsRNA and that RIG-I is activated by viral genomic single-stranded RNA (ssRNA) bearing 5′-phosphates, and suggested that its ability to sense 5'-phosphorylated RNA evolved in the innate immune system as a means of discriminating between self and nonself.

Nonself RNA-sensing mechanism of RIG-I helicase and activation of antiviral immune responses.

Small self-RNA generated by RNase L amplifies antiviral innate immunity

It is shown that small self-RNAs produced by the action of RNase L on cellular RNA induce IFN-β expression and that the signalling involves RIG-I, MDA5 and IPS-1.


How viral replication in cytoplasm is detected by RIG‑I helicase and switch on signal cascades for initial antiviral responses is highlighted.

DEAD-box RNA helicase 21 negatively regulates cytosolic RNA-mediated innate immune signaling

It is demonstrated that DDX21 negatively regulates IFN-β production and functions to maintain immune homeostasis and identified that the 217–784 amino acid region ofDDX21 is essential for binding dsRNA and associated with its ability to antagonize IFN production.

Differential roles of MDA5 and RIG-I helicases in the recognition of RNA viruses

It is found that RIG-I is essential for the production of interferons in response to RNA viruses including paramyxoviruses, influenza virus and Japanese encephalitis virus, whereas MDA5 is critical for picornavirus detection.

DHX36 Enhances RIG-I Signaling by Facilitating PKR-Mediated Antiviral Stress Granule Formation

A novel function of DHX36 is identified as a critical regulator of PKR-dependent avSG to facilitate viral RNA recognition by RIG-I-like receptor (RLR).



PACT, a double-stranded RNA binding protein acts as a positive regulator for type I interferon gene induced by Newcastle disease virus.

It is found that PACT, originally identified as protein activator for dsRNA-dependent protein kinase (PKR) and implicated in theregulation of translation, augmented IFN-beta gene activation induced by Newcastle disease virus is involved in the regulation of viral replication and results in a marked increase of cellular IFn- beta gene expression.

mda-5: An interferon-inducible putative RNA helicase with double-stranded RNA-dependent ATPase activity and melanoma growth-suppressive properties

Human melanoma cells can be reprogrammed to terminally differentiate and irreversibly lose proliferative capacity by appropriate pharmacological manipulation. Subtraction hybridization identified

Triggering the Interferon Antiviral Response Through an IKK-Related Pathway

It is reported here that the IκB kinase (IKK)–related kinases IKKϵ and TANK-binding kinase 1 are components of the virus-activated kinase that phosphorylate IRf-3 and IRF-7.

Innate Antiviral Responses by Means of TLR7-Mediated Recognition of Single-Stranded RNA

These results identify ssRNA as a ligand for TLR7 and suggest that cells of the innate immune system sense endosomal ssRNA to detect infection by RNA viruses.

Direct triggering of the type I interferon system by virus infection: activation of a transcription factor complex containing IRF‐3 and CBP/p300

It is demonstrated that IRF‐3 transmits a virus‐induced signal from the cytoplasm to the nucleus, and it is suggested that IRf‐3 plays an important role in the virus‐inducible primary activation of type I IFN and IFN‐responsive genes.

Recognition of double-stranded RNA and activation of NF-κB by Toll-like receptor 3

It is shown that mammalian TLR3 recognizes dsRNA, and that activation of the receptor induces the activation of NF-κB and the production of type I interferons (IFNs).

Antiviral Actions of Interferons

  • C. Samuel
  • Biology
    Clinical Microbiology Reviews
  • 2001
SUMMARY Tremendous progress has been made in understanding the molecular basis of the antiviral actions of interferons (IFNs), as well as strategies evolved by viruses to antagonize the actions of

Species-Specific Recognition of Single-Stranded RNA via Toll-like Receptor 7 and 8

It is shown that guanosine (G)- and uridine (U)-rich ssRNA oligonucleotides derived from human immunodeficiency virus–1 (HIV-1) stimulate dendritic cells and macrophages to secrete interferon-α and proinflammatory, as well as regulatory, cytokines, and these data suggest that ssRNA represents a physiological ligand for TLR7 and TLR8.