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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >RNAi-mediated immunity provides strong protection against the negative-strand RNA vesicular stomatitis virus in Drosophila
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RNAi-mediated immunity provides strong protection against the negative-strand RNA vesicular stomatitis virus in Drosophila

机译：RNAi介导的免疫力可抵抗果蝇中的负链RNA水疱性口炎病毒

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摘要

Activation of innate antiviral responses in multicellular organisms relies on the recognition of structural differences between viral and cellular RNAs. Double-stranded (ds)RNA, produced during viral replication, is a well-known activator of antiviral defenses and triggers interferon production in vertebrates and RNAi in invertebrates and plants. Previous work in mammalian cells indicates that negative-strand RNA viruses do not appear to generate dsRNA, and that activation of innate immunity is triggered by the recognition of the uncapped 5' ends of viral RNA. This finding raises the question whether antiviral RNAi, which is triggered by the presence of dsRNA in insects, represents an effective host-defense mechanism against negative-strand RNA viruses. Here, we show that the negative-strand RNA virus vesicular stomatitis virus (VSV) does not produce easily detectable amounts of dsRNA in Drosophila cells. Nevertheless, RNAi represents a potent response to VSV infection, as illustrated by the high susceptibility of RNAi-defective mutant flies to this virus. VSV-derived small RNAs produced in infected cells or flies uniformly cover the viral genome, and equally map the genome and antigenome RNAs, indicating that they derive from dsRNA. Our findings reveal that RNAi is not restricted to the defense against positive-strand or dsRNA viruses but can also be highly efficient against a negative-strand RNA virus. This result is of particular interest in view of the frequent transmission of medically relevant negative-strand RNA viruses to humans by insect vectors.
机译：多细胞生物中先天抗病毒应答的激活取决于对病毒和细胞RNA之间结构差异的认识。在病毒复制过程中产生的双链（ds）RNA是众所周知的抗病毒防御激活剂，可触发脊椎动物和无脊椎动物和植物中RNAi的干扰素产生。哺乳动物细胞中的先前工作表明，负链RNA病毒似乎不会产生dsRNA，并且先天免疫的激活是通过识别病毒RNA的未封端5'端而触发的。这一发现提出了一个问题，即由昆虫中存在dsRNA触发的抗病毒RNAi是否代表一种针对负链RNA病毒的有效宿主防御机制。在这里，我们显示出负链RNA病毒水疱性口炎病毒（VSV）在果蝇细胞中不会产生容易检测到的dsRNA。然而，RNAi代表了对VSV感染的有效反应，RNAi缺陷型突变果蝇对这种病毒的高度敏感性证明了这一点。在感染细胞或果蝇中产生的VSV衍生的小RNA均匀地覆盖病毒基因组，并平等地绘制基因组和反基因组RNA，表明它们源自dsRNA。我们的发现表明，RNAi不仅限于对正链或dsRNA病毒的防御，而且还可以对负链RNA病毒高度有效。鉴于昆虫载体将医学上相关的负链RNA病毒频繁传播给人类，因此这一结果特别令人感兴趣。

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    Stefanie Mueller; Valerie Gausson; Nicolas Vodovar; Safia Deddouche; Laurent Troxler; Jonathan Perot; Sebastien Pfeffer; Jules A. Hoffmann; Maria-Carla Saleh; Jean-Luc lmler;

  • 作者单位

    Centre National de la Recherche Scientifique Unite Propre de Recherche 9022;

    lnstitut Pasteur, Viruses and RNA interference and Centre National de la Recherche Scientifique, Unite de Recherche Associee 3015,75015 Paris, France;

    lnstitut Pasteur, Viruses and RNA interference and Centre National de la Recherche Scientifique, Unite de Recherche Associee 3015,75015 Paris, France;

    Centre National de la Recherche Scientifique Unite Propre de Recherche 9022;

    Centre National de la Recherche Scientifique Unite Propre de Recherche 9022;

    Unite Propre de Recherche 9002, Institut de Biologie Moteculaire et Cellulaire du Centre National de la Recherche Scientifique UPR9002, 67084 Strasbourg, France;

    Unite Propre de Recherche 9002, Institut de Biologie Moteculaire et Cellulaire du Centre National de la Recherche Scientifique UPR9002, 67084 Strasbourg, France;

    Centre National de la Recherche Scientifique Unite Propre de Recherche 9022,Faculte des Sciences de la Vie, Universite de Strasbourg, 67000 Strasbourg, France;

    Centre National de la Recherche Scientifique Unite Propre de Recherche 9022;

    Centre National de la Recherche Scientifique Unite Propre de Recherche 9022,Faculte des Sciences de la Vie, Universite de Strasbourg, 67000 Strasbourg, France;

  • 收录信息 美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

    deep sequencing; arbovirus; Dicer-2; AGO2; small RNA profiling;

    机译：深度测序虫媒病毒Dicer-2;AGO2;小RNA分析;

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