RIG-I detects viral genomic RNA during negative-strand RNA virus infection

Cell. 2010 Feb 5;140(3):397-408. doi: 10.1016/j.cell.2010.01.020.


RIG-I is a key mediator of antiviral immunity, able to couple detection of infection by RNA viruses to the induction of interferons. Natural RIG-I stimulatory RNAs have variously been proposed to correspond to virus genomes, virus replication intermediates, viral transcripts, or self-RNA cleaved by RNase L. However, the relative contribution of each of these RNA species to RIG-I activation and interferon induction in virus-infected cells is not known. Here, we use three approaches to identify physiological RIG-I agonists in cells infected with influenza A virus or Sendai virus. We show that RIG-I agonists are exclusively generated by the process of virus replication and correspond to full-length virus genomes. Therefore, nongenomic viral transcripts, short replication intermediates, and cleaved self-RNA do not contribute substantially to interferon induction in cells infected with these negative strand RNA viruses. Rather, single-stranded RNA viral genomes bearing 5'-triphosphates constitute the natural RIG-I agonists that trigger cell-intrinsic innate immune responses during infection.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line
  • DEAD Box Protein 58
  • DEAD-box RNA Helicases / immunology*
  • Dogs
  • Humans
  • Interferons / immunology
  • Membrane Proteins / immunology*
  • Mice
  • Nerve Tissue Proteins / immunology*
  • RNA Virus Infections / immunology*
  • RNA Viruses / physiology
  • RNA, Viral / immunology*
  • Virus Replication


  • Membrane Proteins
  • Nerve Tissue Proteins
  • RNA, Viral
  • Robo3 protein, mouse
  • Interferons
  • DDX58 protein, human
  • DEAD Box Protein 58
  • DEAD-box RNA Helicases