Institut Pasteur, Viruses and RNA Interference, Centre National de la Recherche Scientifique UMR 3569, 75015 Paris, France; Institut Pasteur, Viral Populations and Pathogenesis, Centre National de la Recherche Scientifique UMR 3569, 75015 Paris, France; University of Paris Diderot, Sorbonne Paris Cité, Cellule Pasteur, 75013 Paris, France.
Institut Pasteur, Viruses and RNA Interference, Centre National de la Recherche Scientifique UMR 3569, 75015 Paris, France.
Cell Host Microbe. 2018 Mar 14;23(3):353-365.e8. doi: 10.1016/j.chom.2018.02.001. Epub 2018 Mar 1.
The RNAi pathway confers antiviral immunity in insects. Virus-specific siRNA responses are amplified via the reverse transcription of viral RNA to viral DNA (vDNA). The nature, biogenesis, and regulation of vDNA are unclear. We find that vDNA produced during RNA virus infection of Drosophila and mosquitoes is present in both linear and circular forms. Circular vDNA (cvDNA) is sufficient to produce siRNAs that confer partially protective immunity when challenged with a cognate virus. cvDNAs bear homology to defective viral genomes (DVGs), and DVGs serve as templates for vDNA and cvDNA synthesis. Accordingly, DVGs promote the amplification of vDNA-mediated antiviral RNAi responses in infected Drosophila. Furthermore, vDNA synthesis is regulated by the DExD/H helicase domain of Dicer-2 in a mechanism distinct from its role in siRNA generation. We suggest that, analogous to mammalian RIG-I-like receptors, Dicer-2 functions like a pattern recognition receptor for DVGs to modulate antiviral immunity in insects.
RNAi 途径赋予昆虫抗病毒免疫能力。病毒特异性 siRNA 反应通过病毒 RNA 的反转录扩增为病毒 DNA（vDNA）。vDNA 的性质、生物发生和调控尚不清楚。我们发现，在果蝇和蚊子的 RNA 病毒感染过程中产生的 vDNA 以线性和环状两种形式存在。当受到同源病毒的挑战时，环状 vDNA（cvDNA）足以产生部分保护性免疫的 siRNA。cvDNAs 与缺陷病毒基因组（DVGs）具有同源性，DVGs 是 vDNA 和 cvDNA 合成的模板。因此，DVGs 促进了感染果蝇中 vDNA 介导的抗病毒 RNAi 反应的扩增。此外，vDNA 的合成受 Dicer-2 的 DExD/H 解旋酶结构域的调控，这一机制与 Dicer-2 在 siRNA 生成中的作用不同。我们认为，类似于哺乳动物的 RIG-I 样受体，Dicer-2 作为 DVG 的模式识别受体，在昆虫中发挥作用，调节抗病毒免疫。
