The RNA silencing endonuclease Argonaute 2 mediates specific antiviral immunity in Drosophila melanogaster.
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.
van Rij
Ronald P
RP
Department of Microbiology and Immunology, University of California at San Francisco, San Francisco, CA 94143, USA.
Saleh
Maria-Carla
MC
Berry
Bassam
B
Foo
Catherine
C
Houk
Andrew
A
Antoniewski
Christophe
C
Andino
Raul
R
D000818:Animals; D060565:Argonaute Proteins; D029721:Drosophila Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D004331:Drosophila melanogaster / Q000201:enzymology* / Q000276:immunology* / Q000821:virology; D020868:Gene Silencing; D007304:Insect Viruses / Q000235:genetics / Q000276:immunology*; D020365:RNA Helicases / Q000037:antagonists & inhibitors; D034622:RNA Interference; D012330:RNA, Double-Stranded / Q000378:metabolism; D012367:RNA, Viral / Q000378:metabolism; D034743:RNA-Induced Silencing Complex / Q000235:genetics / Q000502:physiology*; D043244:Ribonuclease III; D013489:Suppression, Genetic; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism
C433807:AGO2 protein, Drosophila; D060565:Argonaute Proteins; D029721:Drosophila Proteins; D012330:RNA, Double-Stranded; D012367:RNA, Viral; D034743:RNA-Induced Silencing Complex; D014764:Viral Proteins; C478069:DCR-2 protein, Drosophila; D043244:Ribonuclease III; D020365:RNA Helicases