Invertebrates mainly rely on sequence-specific RNA interference (RNAi) to resist viral infections. Increasing studies show that double-stranded RNA (dsRNA) can induce sequence-independent protection and that Dicer-2, the key RNAi player that cleaves long dsRNA into small interfering RNA (siRNA), is necessary for this protection. However, how this protection occurs remains unknown. Herein, we report that it is caused by adenosine triphosphate (ATP)-hydrolysis accompanying the dsRNA-cleavage. Dicer-2 helicase domain is ATP-dependent; therefore, the cleavage consumes ATP. ATP depletion activates adenosine monophosphate-activated protein kinase (Ampk) and induces nuclear localization of Fork head box O (FoxO), a key transcriptional factor for dsRNA-induced genes. siRNAs that do not require processing cannot activate the transcriptional response. This study reveals a unique nonspecific antiviral mechanism other than the specific RNAi in shrimp. This mechanism is functionally similar to, but mechanistically different from, the dsRNA-activated antiviral response in vertebrates and suggests an interesting evolution of innate antiviral immunity.

中文翻译：

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双链RNA通过节肢动物的Dicer-2/Ampk/FoxO轴诱导抗病毒转录反应


无脊椎动物主要依靠序列特异性RNA干扰（RNAi）来抵抗病毒感染。越来越多的研究表明，双链 RNA (dsRNA) 可以诱导序列无关的保护，而 Dicer-2（将长 dsRNA 切割成小干扰 RNA (siRNA) 的关键 RNAi 因子）对于这种保护是必需的。然而，这种保护是如何发生的仍然未知。在此，我们报告它是由三磷酸腺苷 (ATP) 水解伴随 dsRNA 裂解引起的。 Dicer-2 解旋酶结构域是 ATP 依赖性的；因此，裂解会消耗 ATP。 ATP 耗尽会激活单磷酸腺苷激活蛋白激酶 (Ampk) 并诱导 Fork 头盒 O (FoxO) 的核定位，FoxO 是 dsRNA 诱导基因的关键转录因子。不需要加工的 siRNA 无法激活转录反应。这项研究揭示了虾中除特异性 RNAi 之外的独特非特异性抗病毒机制。这种机制在功能上类似于脊椎动物中 dsRNA 激活的抗病毒反应，但在机制上有所不同，并表明先天抗​​病毒免疫的有趣进化。