The RNA silencing endonuclease Argonaute 2 mediates specific antiviral immunity in Drosophila melanogaster

Abstract

Most organisms have evolved defense mechanisms to protect themselves from viruses and other pathogens.Arthropods lack the protein-based adaptive immune response found in vertebrates. Here we show that the central catalytic component of the RNA-induced silencing complex (RISC), the nuclease Argonaute 2 (Ago-2), is essential for antiviral defense in adult Drosophila melanogaster. Ago-2-defective flies are hypersensitive to infection with a major fruit fly pathogen, Drosophila C virus (DCV), and with Cricket Paralysis virus (CrPV). Increased mortality in ago-2 mutant flies was associated with a dramatic increase in viral RNA accumulation and virus titers. The physiological significance of this antiviral mechanism is underscored by our finding that DCV encodes a potent suppressor of RNA interference (RNAi). This suppressor binds long double-stranded RNA (dsRNA) and inhibits Dicer-2-mediated processing of dsRNA into short interfering RNA (siRNA), but does not bind short siRNAs or disrupt the microRNA (miRNA) pathway. Based on these results we propose that RNAi is a major antiviral immune defense mechanism in Drosophila.

Chromatin organization at the nuclear periphery as revealed by image analysis of structured illumination microscopy data

“…In yeast, the heterochromatic repeats need to be transcribed to generate siRNA that positively regulates heterochromatin formation (Volpe et al, 2002). A similar system has been described in Drosophila (Pal-Bhadra et al, 2004;van Rij et al, 2006;Wang et al, 2006). The described mechanisms involve deactylation of H3K9Ac by HDAC1, demethylation of H3K4 by LSD1 and KDM2A, methylation of H3K9 or H3K23 and binding of HP1 (Schotta et al, 2004).…”

Isolation and characterization of Argonaute 2: A key gene of the RNA interference pathway in the rare minnow, Gobiocypris rarus

“…Ago2-defective flies are hypersensitive to infection with a major fruit fly pathogen, Drosophila C virus (DCV), Flock House virus (FHV), and with Cricket Paralysis virus (CrPV). Increased mortality in ago2 mutant flies was associated with a dramatic increase in viral RNA accumulation and virus titers [21,22]. In fishes, Argonaute family homologous sequences were only found from three species in GenBank searched by Blastp.…”

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

“…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]. The first genome-wide RNAi screen for host factors that impact pathogen replication was performed using DCV infection of S2 cells [53].…”