The RNA silencing endonuclease Argonaute 2 mediates specific antiviral immunity in Drosophila melanogaster
The RNA silencing endonuclease Argonaute 2 mediates specific antiviral immunity in Drosophila melanogaster
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DOI：
10.1101/gad.1482006
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发表时间：
2006-11-01
影响因子：
10.5
通讯作者：
Andino, Raul
中科院分区：
文献类型：
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作者：
van Rij, Ronald P.;Saleh, Maria-Carla;Andino, Raul
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。在这里，我们证明了 RNA 诱导沉默复合物 (RISC) 的核心催化成分，核酸酶 Argonaute 2 (Ago-2)，对于成年果蝇的抗病毒防御至关重要。 Ago-2 缺陷的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。 ago-2突变果蝇死亡率的增加与病毒RNA积累和病毒滴度的急剧增加有关。我们发现 DCV 编码一种有效的 RNA 干扰 (RNAi) 抑制因子，强调了这种抗病毒机制的生理学意义。该抑制因子结合长双链 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 microRNA (miRNA) 途径。基于这些结果，我们提出 RNAi 是果蝇中主要的抗病毒免疫防御机制。
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.