Control of nonsegmented negative-strand RNA virus replication by siRNA
Control of nonsegmented negative-strand RNA virus replication by siRNA
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DOI：
10.1016/j.virusres.2004.01.012
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发表时间：
2004-06-01
期刊：
影响因子：
5
通讯作者：
Barik, S
中科院分区：
文献类型：
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作者：
Barik, S
我们的实验室首次提供了双链短干扰RNA （ds-siRNA）可以作为有效和特异性抗病毒药物的概念证明。sirna是针对非节段负链RNA （NNR）病毒的特异性mrna设计的，它可以消除相应病毒蛋白的表达，并产生预测的病毒表型。在不同的属中证实了敲除：呼吸道合胞病毒（RSV），一种肺炎病毒；水疱性口炎病毒（VSV），一种横纹肌病毒；人类副流感病毒（HPIV），一种副粘病毒。目标基因可能具有广泛的功能，因此记录了该技术的多功能性。有趣的是，反义单链siRNA （ss-siRNA）也有效，尽管浓度更高。NNR病毒基因组RNA和抗基因组RNA对siRNA具有抗性，它们被核衣壳蛋白封装并作为病毒RNA依赖RNA聚合酶的模板。总之，sirna与难以在NNR病毒中执行的传统突变分析相比具有互补优势，并且也是解剖宿主-病毒相互作用途径的重要新工具。(C) 2004 Elsevier B.V.版权所有
Our laboratory provided the first proof-of-concept that double-stranded short interfering RNA (ds-siRNA) can act as potent and specific antiviral agents. Designed against specific mRNAs of nonsegmented negative-stranded RNA (NNR) viruses, siRNAs abrogated expression of the corresponding viral proteins, and generated the predicted viral phenotypes. Knockdown was demonstrated across different genera: respiratory syncytial virus (RSV), a pneumovirus;, vesicular stomatitis virus (VSV), a rhabdovirus; and human parainfluenza virus (HPIV), a paramyxovirus. The targeted genes could have a wide range of functions, thus documenting the versatility of the technique. Interestingly, antisense single-stranded siRNA (ss-siRNA) was also effective, albeit at a higher concentration. NNR viral genomic and antigenomic RNA, which are encapsidated by nucleocapsid protein and serve as templates for viral RNA-dependent RNA polymerase, were resistant to siRNA. Together, siRNAs offer complementary advantages over traditional mutational analyses that are difficult to perform in NNR viruses, and are also an important new tool to dissect host-virus interactive pathways. (C) 2004 Elsevier B.V. All rights reserved.