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

Genes Dev. 2006 Nov 1;20(21):2985-95. doi: 10.1101/gad.1482006.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Argonaute Proteins
  • Drosophila Proteins / antagonists & inhibitors
  • Drosophila Proteins / genetics
  • Drosophila Proteins / physiology*
  • Drosophila melanogaster / enzymology*
  • Drosophila melanogaster / immunology*
  • Drosophila melanogaster / virology
  • Gene Silencing
  • Insect Viruses / genetics
  • Insect Viruses / immunology*
  • RNA Helicases / antagonists & inhibitors
  • RNA Interference*
  • RNA, Double-Stranded / metabolism
  • RNA, Viral / metabolism
  • RNA-Induced Silencing Complex / genetics
  • RNA-Induced Silencing Complex / physiology*
  • Ribonuclease III
  • Suppression, Genetic
  • Viral Proteins / genetics
  • Viral Proteins / metabolism


  • AGO2 protein, Drosophila
  • Argonaute Proteins
  • Drosophila Proteins
  • RNA, Double-Stranded
  • RNA, Viral
  • RNA-Induced Silencing Complex
  • Viral Proteins
  • DCR-2 protein, Drosophila
  • Ribonuclease III
  • RNA Helicases