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

Ronald P van Rij (1) , Maria-Carla P Saleh (1) , Bassam Berry (2) , Catherine Foo (1) , Andrew Houk (1) , Christophe C. Antoniewski (2) , Raul Andino (1)

1 UC San Francisco - University of California [San Francisco]
2 Biologie du Développement

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.

Mots clés: RNAi suppressor; Antiviral defense; dsRNA-binding domain; Drosophila C virus; Cricket Paralysis virus

Domaines: Virologie; Immunité innée; Immunologie

Ronald P van Rij, Maria-Carla P Saleh, Bassam Berry, Catherine Foo, Andrew Houk, et al.. The RNA silencing endonuclease Argonaute 2 mediates specific antiviral immunity in Drosophila melanogaster. Genes and Development, 2006, 20 (21), pp.2985-2995. ⟨10.1101/gad.1482006⟩. ⟨pasteur-01954329⟩