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

Nat Immunol. 2004 Jul;5(7):730-7. doi: 10.1038/ni1087. Epub 2004 Jun 20.

Abstract

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 signaling. The caspase recruitment domain transmitted 'downstream' signals, resulting in the activation of transcription factors NF-kappaB and IRF-3. Subsequent gene activation by these factors induced antiviral functions, including type I interferon production. Thus, RIG-I is key in the detection and subsequent eradication of the replicating viral genomes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Cells, Cultured
  • DNA-Binding Proteins / metabolism
  • Gene Expression Regulation
  • Genes, Reporter / genetics
  • Humans
  • Interferon Regulatory Factor-3
  • Interferons / biosynthesis
  • Interferons / genetics
  • Interferons / immunology
  • Mice
  • NF-kappa B / metabolism
  • Promoter Regions, Genetic / genetics
  • Protein Structure, Tertiary
  • Proteins / chemistry
  • Proteins / genetics
  • Proteins / metabolism*
  • RNA Helicases / chemistry
  • RNA Helicases / genetics
  • RNA Helicases / metabolism*
  • RNA, Double-Stranded / genetics
  • RNA, Double-Stranded / physiology*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • RNA, Small Interfering / genetics
  • RNA, Small Interfering / metabolism
  • Sequence Deletion
  • Signal Transduction
  • Transcription Factors / metabolism
  • Transcriptional Activation
  • Viruses / growth & development*
  • Viruses / immunology*

Substances

  • DNA-Binding Proteins
  • IRF3 protein, human
  • Interferon Regulatory Factor-3
  • Irf3 protein, mouse
  • NF-kappa B
  • Proteins
  • RAI1 protein, human
  • RNA, Double-Stranded
  • RNA, Messenger
  • RNA, Small Interfering
  • Transcription Factors
  • Interferons
  • RNA Helicases