Inactivation of the type I interferon pathway reveals long double‐stranded RNA ‐mediated RNA interference in mammalian cells
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Volume
35
Pagination
2505 - 2518
Publisher
DOI
10.15252/embj.201695086
Journal
The EMBO Journal
Issue
ISSN
0261-4189
Metadata
Show full item recordAbstract
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not been superseded by vertebrate evolution of the IFN system.
Authors
Maillard, PV; Van der Veen, AG; Deddouche‐Grass, S; Rogers, NC; Merits, A; Reis e Sousa, CCollections
- Centre for Immunobiology [1121]