Shared and unique functions of the DExD/H-box helicases RIG-I, MDA5, and LGP2 in antiviral innate immunity

J Immunol. 2005 Sep 1;175(5):2851-8. doi: 10.4049/jimmunol.175.5.2851.

Abstract

The cellular protein retinoic acid-inducible gene I (RIG-I) senses intracellular viral infection and triggers a signal for innate antiviral responses including the production of type I IFN. RIG-I contains a domain that belongs to a DExD/H-box helicase family and exhibits an N-terminal caspase recruitment domain (CARD) homology. There are three genes encoding RIG-I-related proteins in human and mouse genomes. Melanoma differentiation associated gene 5 (MDA5), which consists of CARD and a helicase domain, functions as a positive regulator, similarly to RIG-I. Both proteins sense viral RNA with a helicase domain and transmit a signal downstream by CARD; thus, these proteins share overlapping functions. Another protein, LGP2, lacks the CARD homology and functions as a negative regulator by interfering with the recognition of viral RNA by RIG-I and MDA5. The nonstructural protein 3/4A protein of hepatitis C virus blocks the signaling by RIG-I and MDA5; however, the V protein of the Sendai virus selectively abrogates the MDA5 function. These results highlight ingenious mechanisms for initiating antiviral innate immune responses and the action of virus-encoded inhibitors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • DEAD Box Protein 58
  • DEAD-box RNA Helicases
  • Humans
  • Immunity, Innate
  • Interferon-Induced Helicase, IFIH1
  • Mice
  • Protein Structure, Tertiary
  • RNA Helicases / chemistry
  • RNA Helicases / physiology*
  • Receptors, Immunologic
  • Signal Transduction
  • Virus Diseases / immunology*

Substances

  • Receptors, Immunologic
  • RIGI protein, human
  • Ddx58 protein, mouse
  • IFIH1 protein, human
  • DEAD Box Protein 58
  • DEAD-box RNA Helicases
  • Interferon-Induced Helicase, IFIH1
  • RNA Helicases