A dsRNA-binding protein of a complex invertebrate DNA virus suppresses the Drosophila RNAi response.

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.

journal_name

Nucleic Acids Res

journal_title

Nucleic acids research

authors

Bronkhorst AW,van Cleef KW,Venselaar H,van Rij RP

doi

10.1093/nar/gku910

subject

Has Abstract

pub_date

2014-10-29 00:00:00

pages

12237-48

issue

19

eissn

0305-1048

issn

1362-4962

pii

gku910

journal_volume

42

pub_type

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