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

  1. Ronald P. van Rij1,
  2. Maria-Carla Saleh1,
  3. Bassam Berry2,
  4. Catherine Foo1,
  5. Andrew Houk1,
  6. Christophe Antoniewski2, and
  7. Raul Andino1,3
  1. 1Department of Microbiology and Immunology, University of California at San Francisco, San Francisco, California 94143, USA;
  2. 2Department of Developmental Biology, Centre national de la recherche scientifique (CNRS) URA 2578 Pasteur Institute, Paris 75015, France

    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.

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