Inactivation of the type I interferon pathway reveals long double-stranded RNA-mediated RNA interference in mammalian cells.
RNA interference (RNAi) elicited by long double-stranded (ds) or base-paired viral RNA constitutes the major mechanism of antiviral defence in plants and invertebrates. In contrast, it is controversial whether it acts in chordates. Rather, in vertebrates, viral RNAs induce a distinct defence system known as the interferon (IFN) response. Here, we tested the possibility that the IFN response masks or inhibits antiviral RNAi in mammalian cells. Consistent with that notion, we find that sequence-specific gene silencing can be triggered by long dsRNAs in differentiated mouse cells rendered deficient in components of the IFN pathway. This unveiled response is dependent on the canonical RNAi machinery and is lost upon treatment of IFN-responsive cells with type I IFN Notably, transfection with long dsRNA specifically vaccinates IFN-deficient cells against infection with viruses bearing a homologous sequence. Thus, our data reveal that RNAi constitutes an ancient antiviral strategy conserved from plants to mammals that precedes but has not been superseded by vertebrate evolution of the IFN system.
Immunobiology Laboratory, The Francis Crick Institute, London, UK caetano@crick.ac.uk pierre.maillard@crick.ac.uk.
Pierre V
PV
Maillard
Immunobiology Laboratory, The Francis Crick Institute, London, UK.
Annemarthe G
AG
Van der Veen
Immunobiology Laboratory, The Francis Crick Institute, London, UK.
Safia
S
Deddouche-Grass
Immunobiology Laboratory, The Francis Crick Institute, London, UK.
Neil C
NC
Rogers
Institute of Technology, University of Tartu, Tartu, Estonia.
Andres
A
Merits
Immunobiology Laboratory, The Francis Crick Institute, London, UK caetano@crick.ac.uk pierre.maillard@crick.ac.uk.
Caetano
0000-0001-7392-2119
C
Reis e Sousa
D000818:Animals; D002478:Cells, Cultured; D005786:Gene Expression Regulation; D007113:Immunity, Innate; D007370:Interferon Type I / Q000037:antagonists & inhibitors; D051379:Mice; D034622:RNA Interference; D012328:RNA Viruses / Q000276:immunology; D012330:RNA, Double-Stranded / Q000378:metabolism*; D012367:RNA, Viral / Q000378:metabolism*
D007370:Interferon Type I; D012330:RNA, Double-Stranded; D012367:RNA, Viral
RNA interference; double‐stranded RNA; innate immunity; viral infection