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Dicer-2-Dependent Generation of Viral DNA from Defective Genomes of RNA Viruses Modulates Antiviral Immunity in Insects

机译:来自RNA病毒的缺陷基因组的Dicer-2依赖性生成病毒性DNA调节昆虫中的抗病毒免疫力

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摘要

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.
机译:RNAI途径赋予昆虫的抗病毒免疫力。通过病毒RNA对病毒DNA(VDNA)的逆转录扩增病毒特异性siRNA响应。 VDNA的性质,生物发生和调节尚不清楚。我们发现在果蝇和蚊子的RNA病毒感染期间产生的VDNA以线性和圆形形式存在。圆形VDNA(CVDNA)足以产生在用同源病毒攻击时赋予部分保护性免疫的siRNA。 CVDNA承受缺陷病毒基因组(DVG)的同源性,DVG用作VDNA和CVDNA合成的模板。因此,DVGS促进在感染的果蝇中的VDNA介导的抗病毒RNAi反应的扩增。此外,VDNA合成由Dicer-2的DEXD / H Helicase结构域在不同于其在siRNA生成中的作用的机制中调节。我们建议,类似于哺乳动物钻机-I相对的受体,Dicer-2就像一种用于DVG的模式识别受体,以调节昆虫中的抗病毒免疫。

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  • 来源
    《Cell Host & Microbe》 |2018年第3期|共20页
  • 作者单位

    Inst Pasteur Viruses &

    RNA Interference CNRS UMR 3569 F-75015 Paris France;

    Inst Pasteur Viruses &

    RNA Interference CNRS UMR 3569 F-75015 Paris France;

    Inst Pasteur Viruses &

    RNA Interference CNRS UMR 3569 F-75015 Paris France;

    Inst Pasteur Viruses &

    RNA Interference CNRS UMR 3569 F-75015 Paris France;

    Inst Pasteur INSERM Immunobiol Dendrit Cells U1223 F-75015 Paris France;

    Inst Pasteur Viruses &

    RNA Interference CNRS UMR 3569 F-75015 Paris France;

    Inst Pasteur Viruses &

    RNA Interference CNRS UMR 3569 F-75015 Paris France;

    Inst Pasteur Viruses &

    RNA Interference Viral Populat &

    Pathogenesis UMR 3569 F-75015 Paris France;

    Iowa State Univ Dept Anim Sci Ames IA 50010 USA;

    Inst Pasteur Viruses &

    RNA Interference Viral Populat &

    Pathogenesis UMR 3569 F-75015 Paris France;

    Univ Perpignan Univ Montpellier LGDP DIADE Inst Rech Dev F-66860 Perpignan France;

    Inst Pasteur Viruses &

    RNA Interference CNRS UMR 3569 F-75015 Paris France;

    Inst Pasteur Insect Virus Interact CNRS URA 3012 F-75015 Paris France;

    Inst Pasteur Insect Virus Interact CNRS URA 3012 F-75015 Paris France;

    Iowa State Univ Dept Anim Sci Ames IA 50010 USA;

    Inst Pasteur Viruses &

    RNA Interference Viral Populat &

    Pathogenesis UMR 3569 F-75015 Paris France;

    Inst Pasteur Viruses &

    RNA Interference CNRS UMR 3569 F-75015 Paris France;

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  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 普通生物学;
  • 关键词

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