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© Institut Pasteur
Phlébotome. Petit diptère de la famille des psychodidés (dans l'Ancien Monde). La femelle hématophage peut être vectrice entre autres de leishmaniose qu'elle transmet par piqûre à un vertébré, chien (hôte principal réservoir), homme ou encore rat (hôtes occasionnels).
Publication : Proceedings of the National Academy of Sciences of the United States of America

The DNA virus Invertebrate iridescent virus 6 is a target of the Drosophila RNAi machinery

Scientific Fields
Diseases
Organisms
Applications
Technique

Published in Proceedings of the National Academy of Sciences of the United States of America - 14 Nov 2012

Bronkhorst AW, van Cleef KW, Vodovar N, Ince IA, Blanc H, Vlak JM, Saleh MC, van Rij RP

Link to Pubmed [PMID] – 23151511

Proc. Natl. Acad. Sci. U.S.A. 2012 Dec;109(51):E3604-13

RNA viruses in insects are targets of an RNA interference (RNAi)-based antiviral immune response, in which viral replication intermediates or viral dsRNA genomes are processed by Dicer-2 (Dcr-2) into viral small interfering RNAs (vsiRNAs). Whether dsDNA virus infections are controlled by the RNAi pathway remains to be determined. Here, we analyzed the role of RNAi in DNA virus infection using Drosophila melanogaster infected with Invertebrate iridescent virus 6 (IIV-6) as a model. We show that Dcr-2 and Argonaute-2 mutant flies are more sensitive to virus infection, suggesting that vsiRNAs contribute to the control of DNA virus infection. Indeed, small RNA sequencing of IIV-6-infected WT and RNAi mutant flies identified abundant vsiRNAs that were produced in a Dcr-2-dependent manner. We observed a highly uneven distribution with strong clustering of vsiRNAs to small defined regions (hotspots) and modest coverage at other regions (coldspots). vsiRNAs mapped in similar proportions to both strands of the viral genome, suggesting that long dsRNA derived from convergent overlapping transcripts serves as a substrate for Dcr-2. In agreement, strand-specific RT-PCR and Northern blot analyses indicated that antisense transcripts are produced during infection. Moreover, we show that vsiRNAs are functional in silencing reporter constructs carrying fragments of the IIV-6 genome. Together, our data indicate that RNAi provides antiviral defense against dsDNA viruses in animals. Thus, RNAi is the predominant antiviral defense mechanism in insects that provides protection against all major classes of viruses.