Essential function in vivo for Dicer-2 in host defense against RNA viruses in drosophila

Abstract

The fruit fly Drosophila melanogaster is a model system for studying innate immunity, including antiviral host defense. Infection with drosophila C virus triggers a transcriptional response that is dependent in part on the Jak kinase Hopscotch. Here we show that successful infection and killing of drosophila with the insect nodavirus flock house virus was strictly dependent on expression of the viral protein B2, a potent inhibitor of processing of double-stranded RNA mediated by the essential RNA interference factor Dicer. Conversely, flies with a loss-of-function mutation in the gene encoding Dicer-2 (Dcr-2) showed enhanced susceptibility to infection by flock house virus, drosophila C virus and Sindbis virus, members of three different families of RNA viruses. These data demonstrate the importance of RNA interference for controlling virus replication in vivo and establish Dcr-2 as a host susceptibility locus for virus infections.

Grass carp reovirus activates RNAi pathway in rare minnow, Gobiocypris rarus

“…Plants use Dicer-like proteins as the central enzymes of RNA silencing, which regulate gene expression and mediate defense against viruses (Blevins et al, 2006). Fruit fly Drosophila melanogaster is a model creature for studying innate immunity, including antiviral host defense (Galiana-Arnoux et al, 2006). RNAi against viruses was reported in adult Drosophila (Wang et al, 2006).…”

Genomic RNAi screening in Drosophila S2 cells: what have we learned about host–pathogen interactions?

“…Importantly, insects are infected by a wide variety of viruses, some of which are insect-specific, but others also infect humans (arthropod-borne). Recent studies have demonstrated that many human viruses can productively infect Drosophila S2 cells including Vesicular Stomatitis Virus, Sindbis Virus, Rift Valley Fever Virus, Dengue virus, West Nile Virus ( [51,52] and our unpublished data). The insect-specific viruses, Flock House Virus and Drosophila C virus (DCV) have also been extensively studied in fruit flies [51][52][53][54][55][56].…”

Diversity, evolution, and therapeutic applications of small RNAs in prokaryotic and eukaryotic immune systems

“…The siRNA corresponded specifically to FHV RNA1, supporting that siRNA opposes the accumulation of FHV RNAs. Additionally, siRNA quantities detected post-infection in Drosophila S2 cells has been shown to correlate with the quantity of dsRNA introduced to the cells [49,89]. It is postulated Dicer-2 and R2D2 are bound to the double-stranded siRNAs, to direct them to the RISC effector [125].…”