Article

Viral suppressors of RNA silencing hinder exogenous and endogenous small RNA pathways in Drosophila.

Institut Pasteur, Drosophila Genetics and Epigenetics, CNRS-URA2578, Paris, France.
PLoS ONE (Impact Factor: 3.53). 02/2009; 4(6):e5866. DOI: 10.1371/journal.pone.0005866
Source: PubMed

ABSTRACT In plants and insects, RNA interference (RNAi) is the main responder against viruses and shapes the basis of antiviral immunity. Viruses counter this defense by expressing viral suppressors of RNAi (VSRs). While VSRs in Drosophila melanogaster were shown to inhibit RNAi through different modes of action, whether they act on other silencing pathways remained unexplored.
Here we show that expression of various plant and insect VSRs in transgenic flies does not perturb the Drosophila microRNA (miRNA) pathway; but in contrast, inhibits antiviral RNAi and the RNA silencing response triggered by inverted repeat transcripts, and injection of dsRNA or siRNA. Strikingly, these VSRs also suppressed transposon silencing by endogenous siRNAs (endo-siRNAs).
Our findings identify VSRs as tools to unravel small RNA pathways in insects and suggest a cosuppression of antiviral RNAi and endo-siRNA silencing by viruses during fly infections.

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    ABSTRACT: Invertebrate RNA viruses are targets of the host RNA interference (RNAi) pathway, which limits virus infection by degrading viral RNA substrates. Several insect RNA viruses encode suppressor proteins to counteract this antiviral response. We recently demonstrated that the dsDNA virus Invertebrate iridescent virus 6 (IIV-6) induces an RNAi response in Drosophila. Here, we show that RNAi is suppressed in IIV-6-infected cells and we mapped RNAi suppressor activity to the viral protein 340R. Using biochemical assays, we reveal that 340R binds long dsRNA and prevents Dicer-2-mediated processing of long dsRNA into small interfering RNAs (siRNAs). We demonstrate that 340R additionally binds siRNAs and inhibits siRNA loading into the RNA-induced silencing complex. Finally, we show that 340R is able to rescue a Flock House virus replicon that lacks its viral suppressor of RNAi. Together, our findings indicate that, in analogy to RNA viruses, DNA viruses antagonize the antiviral RNAi response.
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    ABSTRACT: The host RNA interference (RNAi) pathway of insects senses virus infection and induces an antiviral response to restrict virus replication. Dicer-2 detects viral double-stranded RNA, produced by RNA and DNA viruses, and generates viral small interfering RNAs (vsiRNAs). Recent small RNA profiling studies provided new insights into the viral RNA substrates that trigger vsiRNA biogenesis. The importance of the antiviral RNAi pathway is underscored by the observation that viruses have evolved sophisticated mechanisms to counteract this small RNA-based immune response. More recently, it was proposed that another small RNA silencing mechanism, the piRNA pathway, also processes viral RNAs in Drosophila and mosquitoes. Here, we review recent insights into the mechanism of antiviral RNAi, viral small RNA profiles, and viral counter-defense mechanisms in insects.
    Current opinion in virology. 04/2014; 7C:19-28.

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