Activation of RIG-I-like receptor signal transduction

Annie M. Bruns, Curt M. Horvath*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

74 Scopus citations

Abstract

Mammalian cells have the ability to recognize virus infection and mount a powerful antiviral response. Pattern recognition receptor proteins detect molecular signatures of virus infection and activate antiviral signaling cascades. The RIG-I-like receptors are cytoplasmic DExD/H box proteins that can specifically recognize virus-derived RNA species as a molecular feature discriminating the pathogen from the host. The RIG-I-like receptor family is composed of three homologous proteins, RIG-I, MDA5, and LGP2. All of these proteins can bind double-stranded RNA species with varying affinities via their conserved DExD/H box RNA helicase domains and C-terminal regulatory domains. The recognition of foreign RNA by the RLRs activates enzymatic functions and initiates signal transduction pathways resulting in the production of antiviral cytokines and the establishment of a broadly effective cellular antiviral state that protects neighboring cells from infection and triggers innate and adaptive immune systems. The propagation of this signal via the interferon antiviral system has been studied extensively, while the precise roles for enzymatic activities of the RNA helicase domain in antiviral responses are only beginning to be elucidated. Here, current models for RLR ligand recognition and signaling are reviewed.

Original languageEnglish (US)
Pages (from-to)194-206
Number of pages13
JournalCritical Reviews in Biochemistry and Molecular Biology
Volume47
Issue number2
DOIs
StatePublished - Mar 2012

Funding

The authors report no declarations of interest. Research on the RLRs and antiviral responses in the Horvath lab are funded by NIH grants AI073919, AI050707, IMVC Pilot Project AI083005 to CMH. AMB is supported in part by the NIH Cellular and Molecular Basis of Disease Training Grant GM08061.

Keywords

  • LGP2
  • MDA5
  • RIG-I
  • RLR
  • interferon

ASJC Scopus subject areas

  • Molecular Biology
  • Biochemistry

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