RIG-I-mediated antiviral responses to single-stranded RNA bearing 5'-phosphates.
Double-stranded RNA (dsRNA) produced during viral replication is believed to be the critical trigger for activation of antiviral immunity mediated by the RNA helicase enzymes retinoic acid-inducible gene I (RIG-I) and melanoma differentiation-associated gene 5 (MDA5). We showed that influenza A virus infection does not generate dsRNA and that RIG-I is activated by viral genomic single-stranded RNA (ssRNA) bearing 5'-phosphates. This is blocked by the influenza protein nonstructured protein 1 (NS1), which is found in a complex with RIG-I in infected cells. These results identify RIG-I as a ssRNA sensor and potential target of viral immune evasion and suggest that its ability to sense 5'-phosphorylated RNA evolved in the innate immune system as a means of discriminating between self and nonself.
Pichlmair
Andreas
A
Immunobiology Laboratory, Cancer Research UK, London Research Institute, London WC2A 3PX, UK.
Schulz
Oliver
O
Tan
Choon Ping
CP
Näslund
Tanja I
TI
Liljeström
Peter
P
Weber
Friedemann
F
Reis e Sousa
Caetano
C
D000818:Animals; D002460:Cell Line; D002478:Cells, Cultured; D003593:Cytoplasm / Q000378:metabolism / Q000821:virology; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases / Q000235:genetics / Q000378:metabolism*; D003713:Dendritic Cells / Q000821:virology; D004686:Encephalomyocarditis virus / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D016679:Genome, Viral; D006801:Humans; D007113:Immunity, Innate; D009980:Influenza A virus / Q000235:genetics* / Q000276:immunology* / Q000378:metabolism / Q000502:physiology; D016898:Interferon-alpha / Q000096:biosynthesis; D016899:Interferon-beta / Q000096:biosynthesis; D051379:Mice; D008810:Mice, Inbred C57BL; D010710:Phosphates / Q000378:metabolism; D010766:Phosphorylation; D012315:RNA Caps / Q000378:metabolism; D012330:RNA, Double-Stranded / Q000378:metabolism; D012367:RNA, Viral / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011971:Receptors, Immunologic; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D014162:Transfection; D014721:Vesicular stomatitis Indiana virus / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D017361:Viral Nonstructural Proteins / Q000235:genetics / Q000378:metabolism; D014779:Virus Replication
C085820:INS1 protein, influenza virus; D016898:Interferon-alpha; D010710:Phosphates; D012315:RNA Caps; D012330:RNA, Double-Stranded; D012367:RNA, Viral; D011971:Receptors, Immunologic; D011993:Recombinant Fusion Proteins; D017361:Viral Nonstructural Proteins; D016899:Interferon-beta; C452820:RIGI protein, human; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases