RNA interference, arthropod-borne viruses, and mosquitoes
RNA interference, arthropod-borne viruses, and mosquitoes
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DOI：
10.1016/j.virusres.2004.01.017
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发表时间：
2004-06-01
期刊：
影响因子：
5
通讯作者：
Olson, KE
中科院分区：
文献类型：
--
作者：
Sanchez-Vargas, I;Travanty, EA;Olson, KE
RNA干扰（RNAi）可能在大多数真核生物中起抗病毒机制的作用。蚊子体内这种抗病毒途径活性的变化可以部分解释为什么有些蚊子是医学上重要的节肢动物传播病毒（虫媒病毒）的有效载体，而另一些蚊子则不是。有三条证据表明，在传播虫媒病毒的伊蚊物种中存在RNAi途径。首先，重组Sindbis病毒表达基因无关的DENV-2病毒（DENV-2）的RNA片段，通过类似于在植物中描述的病毒诱导基因沉默的机制干扰埃及伊蚊中DENV-2的复制。第二，用双链RNA或合成的来自虫媒病毒基因组的小干扰RNA转染C6/36（白纹伊蚊）细胞会干扰同源病毒的复制。第三，从质粒转录的发夹型denv -2特异性RNA可以产生抗病毒的C6/36细胞。我们假设可以培育转基因蚊子，使其在摄入血液后不久转录黄病毒特异性dsRNA，从而触发RNAi反应。这可以在病毒感染建立之前诱导9中肠的RNAi通路，并深刻改变载体的能力。为了实现这一目标，我们正在利用RNAi途径开发对DENV具有抗性的转基因埃及伊蚊系。(C) 2004 Elsevier B.V.版权所有
RNA interference (RNAi) probably functions as an antiviral mechanism in most eukaryotic organisms. Variations in the activity of this antiviral pathway in mosquitoes could explain, in part, why some mosquitoes are competent vectors of medically important, arthropod-borne viruses (arboviruses) and others are not. There are three lines of evidence that show the RNAi pathway exists in Aedes species that transmit arboviruses. The first is that recombinant Sindbis viruses expressing a RNA fragment from a genetically unrelated dengue-2 virus (DENV-2) interfere with DENV-2 replication in Aedes aegypti mosquitoes by a mechanism similar to virus-induced gene silencing described in plants. The second is that transfection of C6/36 (Aedes albopictus) cells with either double-stranded RNA or synthetic small interfering RNAs derived from an arbovirus genome interferes with replication of the homologous virus. The third is that a hairpin DENV-2-specific RNA transcribed from a plasmid can generate virus-resistant C6/36 cells. We hypothesize that genetically modified mosquitoes can be generated that transcribe a flavivirus-specific dsRNA, triggering the RNAi response, soon after ingestion of a blood meal. This could induce the RNAi pathway in the 9 midgut prior to establishment of virus infection and profoundly change vector competence. Towards this goal, we are developing transgenic A. aegypti lines that are refractory to DENV by exploiting the RNAi pathway. (C) 2004 Elsevier B.V. All rights reserved.