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

  title={RIG-I-Mediated Antiviral Responses to Single-Stranded RNA Bearing 5'-Phosphates},
  author={Andreas Pichlmair and Oliver Schulz and Choon Ping Tan and Tanja I. Näslund and Peter Liljestr{\"o}m and Friedemann Weber and Caetano Reis e Sousa},
  pages={1001 - 997}
Double-stranded RNA (dsRNA) produced during viral replication is believed to be the critical trigger for activation of antiviral immunity mediated by the RNA helicase enzymes retinoic acid–inducible gene I (RIG-I) and melanoma differentiation–associated gene 5 (MDA5). We showed 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. This is blocked by the influenza protein nonstructured protein 1… 

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.

RIG-I dependent sensing of poly ( dAdT ) via the induction of an RNA polymerase III transcribed RNA intermediate

This work has identified a novel DNA sensing pathway involving RNA polymerase III and RIG-I, which plays a pivotal role in coordinating anti-viral defenses in the innate immune response.

RIG-I ATPase Activity and Discrimination of Self-RNA versus Non-Self-RNA

The determinants of this discrimination and how RIG-I ATPase activity contributes to its activation in a manner restricted to its interaction with non-self-RNAs are studied, showing how the innate immune response evolves during infection via IFN expression, from a state in which discrimination of self-RNA from non- Self RNA is most important to one in which this discrimination is sacrificed for the effectiveness of the antiviral response.

Differential recognition of viral RNA by RIG-I

It is shown that in Sendai virus infected cells, RIG-I specifically and preferentially associated with the copy-back defective interfering (DI) particle RNA and not with the full-length Sendai viruses genome or Sendaiirus encoded mRNAs.

Activation and Antagonism of RIG-I-Mediated Innate Immune Signaling by Herpes Simplex Virus 1

The data show that viral infection can lead to deshielding of endogenous RNAs that activate innate immunity, and depletion of endogenous RNA5SP141 strongly dampened the antiviral response to HSV-1 and the related Epstein-Barr virus, as well as influenza A virus, an RNA virus.

Cytoplasmic Sensing of Viral Double-Stranded RNA and Activation of Innate Immunity by RIG-I-Like Receptors

The structure and function of RLRs are reviewed, including retinoic acid-inducible gene-I (RIG-I), melanoma differentiation associated gene 5 (MDA5), and laboratory of genetics and physiology 2 (LGP2), which senses viral double-stranded RNA and triggers an antiviral program including the production of IFN.

Viral unmasking of cellular 5S rRNA pseudogene transcripts induces RIG-I mediated immunity

The findings reveal that antiviral immunity can be triggered by host RNAs that are unshielded following depletion of their respective binding proteins by the virus.

Phosphorylation-Mediated Negative Regulation of RIG-I Antiviral Activity

The results indicate that Thr-170 phosphorylation and TRIM25-mediated Lys-172 ubiquitination of RIG-I functionally antagonize each other, which keeps Rig-I latent, and enables R IG-I to form a stable complex with MAVS, thereby inducing IFN signal transduction.

The RNA Helicase DDX6 Associates with RIG-I to Augment Induction of Antiviral Signaling

Findings imply a novel function for DDX6 as an RNA co-sensor and signaling enhancer for RIG-I, which is a known component of cytoplasmic mRNA-ribonucleoprotein granules like P-bodies and stress granules (SGs).



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

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

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.

The RNA Helicase Lgp2 Inhibits TLR-Independent Sensing of Viral Replication by Retinoic Acid-Inducible Gene-I1

It is proposed that Lgp2 acts as a negative feedback regulator of antiviral signaling by sequestering dsRNA from RIG-I, and inhibits SV and Newcastle disease virus signaling to IFN-stimulated regulatory element- and NF-κB-dependent pathways.

A Toll-like receptor–independent antiviral response induced by double-stranded B-form DNA

It is shown that intracellular administration of double-stranded B-form DNA triggered antiviral responses including production of type I interferons and chemokines independently of Toll-like receptors or the helicase RIG-I.

Essential role of mda-5 in type I IFN responses to polyriboinosinic:polyribocytidylic acid and encephalomyocarditis picornavirus.

It is shown that mda-5 is the dominant receptor mediating type I IFN secretion in response to polyI:C in vitro and in vivo, and selectively impaired antiviral response to encephalomyocarditis picornavirus is exhibited, indicating functional specialization of mda -5 in vivo.

Shared and Unique Functions of the DExD/H-Box Helicases RIG-I, MDA5, and LGP2 in Antiviral Innate Immunity1

The results highlight ingenious mechanisms for initiating antiviral innate immune responses and the action of virus-encoded inhibitors.

Innate Cellular Response to Virus Particle Entry Requires IRF3 but Not Virus Replication

It is shown that the entry of enveloped virus particles from diverse virus families elicits a similar innate response to IRF3, but not IRF1, IRF7, or IRF9, and that subsequent virus replication results in posttranslational modification of IRf3, such as hyperphosphorylation, depending on the nature of the incoming virus.

Double-Stranded RNA Is Produced by Positive-Strand RNA Viruses and DNA Viruses but Not in Detectable Amounts by Negative-Strand RNA Viruses

Investigation of the presence and localization of ds RNA in cells infected with a range of viruses, employing a dsRNA-specific antibody for immunofluorescence analysis revealed that significant amounts ofdsRNA can be detected for viruses with a genome consisting of positive-strand RNA, dsRNAs, or DNA; Surprisingly, however, no DsRNA signals were detected for negative-stranded RNA viruses.

Interferon induction by siRNAs and ssRNAs synthesized by phage polymerase

An improved method for T7 siRNA synthesis is described that alleviates the interferon response while maintaining full efficacy of the siRNAs.