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Inactivation of the type I interferon pathway reveals long double-stranded RNA-mediated RNA interference in mammalian cells.

Maillard, PV; Van der Veen, AG; Deddouche-Grass, S; Rogers, NC; Merits, A; Reis E Sousa, C; (2016) Inactivation of the type I interferon pathway reveals long double-stranded RNA-mediated RNA interference in mammalian cells. The EMBO Journal , 35 (23) pp. 2505-2518. 10.15252/embj.201695086. Green open access

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Abstract

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that RNAi constitutes an ancient antiviral strategy conserved from plants to mammals that precedes but has not been superseded by vertebrate evolution of the IFN system.

Type: Article
Title: Inactivation of the type I interferon pathway reveals long double-stranded RNA-mediated RNA interference in mammalian cells.
Location: England
Open access status: An open access version is available from UCL Discovery
DOI: 10.15252/embj.201695086
Publisher version: http://dx.doi.org/10.15252/embj.201695086
Language: English
Additional information: © 2016 The Authors. Published under the terms of the CC BY 4.0 license. This is an open access article under the terms of the Creative Commons Attribution 4.0 License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
Keywords: RNA interference, double‐stranded RNA, innate immunity, viral infection, Animals, Cells, Cultured, Gene Expression Regulation, Immunity, Innate, Interferon Type I, Mice, RNA Interference, RNA Viruses, RNA, Double-Stranded, RNA, Viral
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Infection and Immunity
URI: https://discovery.ucl.ac.uk/id/eprint/10022840
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