The RNA silencing endonuclease Argonaute 2 mediates specific antiviral immunity in Drosophila melanogaster
| Autor: | Maria-Carla Saleh, Bassam Berry, Catherine K. Foo, Christophe Antoniewski, Raul Andino, Andrew R. Houk, Ronald P. van Rij |
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| Přispěvatelé: | University of California [San Francisco] (UC San Francisco), University of California (UC), Biologie du Développement, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), This work was financially supported by the Pasteur Institute and the CNRS, and by a grant from the ARC (#3203) to C.A. and NIH grants AI40085 and AI064738 to R.A., We thank members of the Andino and Pat O'Farrell laboratory for discussions, technical support, and advice on fly work. We thank O. Voinnet and J.L. Imler for helpful discussions. We thank Judith Frydman and Annemieke Jansens for critical reading the manuscript. Peter Sarnow and Sarah Cherry kindly provided DCV and CrPV virus stocks. We are grateful to C. Vaury for the gift of the B2 DNA, and to D. Fagegaltier, L. Röder, E. Georgenthum, and the BestGene, Inc., for generating transgenic flies. Armin Hekele prepared some of the dsRNA used in this study. We thank Richard Carthew for providing the GMR-wIR fly stock, and Phil Zamore for providing fly RNAi mutants and experimental advice on the Dicer assays in S2 cell extracts. B.B. is a Lebanese CNRSL fellow., University of California [San Francisco] (UCSF), University of California, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS) |
| Jazyk: | angličtina |
| Rok vydání: | 2006 |
| Předmět: |
Ribonuclease III
Small interfering RNA [SDV.IMM.II]Life Sciences [q-bio]/Immunology/Innate immunity Suppression Genetic MESH: Argonaute Proteins MESH: Ribonuclease III RNA interference Drosophila Proteins MESH: Animals MESH: Gene Silencing MESH: Suppression Genetic 0303 health sciences MESH: RNA Helicases 030302 biochemistry & molecular biology Cricket Paralysis virus Argonaute 3. Good health RNA silencing Drosophila melanogaster Drosophila C virus MESH: RNA Viral Argonaute Proteins [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology RNA Viral [SDV.IMM]Life Sciences [q-bio]/Immunology RNA Interference RNA Helicases Research Paper dsRNA-binding domain RNA-induced silencing complex MESH: Drosophila Proteins Trans-acting siRNA MESH: RNA Interference Insect Viruses Biology MESH: Drosophila melanogaster Viral Proteins 03 medical and health sciences MESH: RNA Double-Stranded Antiviral defense Genetics Animals RNA-Induced Silencing Complex RasiRNA RNAi suppressor Gene Silencing RNA Double-Stranded 030304 developmental biology fungi MESH: Insect Viruses MESH: RNA-Induced Silencing Complex biology.organism_classification Virology MESH: Viral Proteins Developmental Biology |
| Zdroj: | Genes and Development Genes and Development, 2006, 20 (21), pp.2985-2995. ⟨10.1101/gad.1482006⟩ Genes and Development, Cold Spring Harbor Laboratory Press, 2006, 20 (21), pp.2985-2995. ⟨10.1101/gad.1482006⟩ |
| ISSN: | 0890-9369 |
| DOI: | 10.1101/gad.1482006⟩ |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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