van Rij Ronald P, Saleh Maria-Carla, Berry Bassam, Foo Catherine, Houk Andrew, Antoniewski Christophe, Andino Raul
Department of Microbiology and Immunology, University of California at San Francisco, San Francisco, CA 94143, USA.
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.
大多数生物体已经进化出防御机制来保护自己免受病毒和其他病原体的侵害。节肢动物缺乏脊椎动物中基于蛋白质的适应性免疫反应。在此我们表明，RNA诱导沉默复合体（RISC）的核心催化成分，核酸酶AGO2，对于成年黑腹果蝇的抗病毒防御至关重要。AGO2缺陷型果蝇对主要果蝇病原体果蝇C病毒（DCV）和蟋蟀麻痹病毒（CrPV）的感染高度敏感。AGO2突变果蝇死亡率的增加与病毒RNA积累和病毒滴度的显著增加有关。我们发现DCV编码一种强大的RNA干扰（RNAi）抑制剂，这突出了这种抗病毒机制的生理意义。这种抑制剂结合长双链RNA（dsRNA）并抑制Dicer-2介导的dsRNA加工成短干扰RNA（siRNA），但不结合短siRNA或破坏微小RNA（miRNA）途径。基于这些结果，我们提出RNAi是果蝇中的一种主要抗病毒免疫防御机制。
