RIG-I detects viral genomic RNA during negative-strand RNA virus infection.
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.
Immunobiology Laboratory, Cancer Research UK London Research Institute, 44 Lincoln's Inn Fields, London WC2A3PX, UK.
Jan
J
Rehwinkel
Choon Ping
CP
Tan
Delphine
D
Goubau
Oliver
O
Schulz
Andreas
A
Pichlmair
Katja
K
Bier
Nicole
N
Robb
Frank
F
Vreede
Wendy
W
Barclay
Ervin
E
Fodor
Caetano
C
Reis e Sousa
D000818:Animals; D002460:Cell Line; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases / Q000276:immunology*; D004285:Dogs; D006801:Humans; D007372:Interferons / Q000276:immunology; D008565:Membrane Proteins / Q000276:immunology*; D051379:Mice; D009419:Nerve Tissue Proteins / Q000276:immunology*; D012327:RNA Virus Infections / Q000276:immunology*; D012328:RNA Viruses / Q000502:physiology; D012367:RNA, Viral / Q000276:immunology*; D011956:Receptors, Cell Surface; D011971:Receptors, Immunologic; D014779:Virus Replication; D000097905:Roundabout Proteins
D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases; D007372:Interferons; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D012367:RNA, Viral; D011956:Receptors, Cell Surface; D011971:Receptors, Immunologic; C118348:Robo3 protein, mouse; D000097905:Roundabout Proteins; C452820:RIGI protein, human