Schott Daniel H, Cureton David K, Whelan Sean P, Hunter Craig P
Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138, USA.
Proc Natl Acad Sci U S A. 2005 Dec 20;102(51):18420-4. doi: 10.1073/pnas.0507123102. Epub 2005 Dec 9.
RNA interference (RNAi) is a sequence-specific gene-silencing mechanism triggered by exogenous dsRNA. In plants an RNAi-like mechanism defends against viruses, but the hypothesis that animals possess a similar natural antiviral mechanism related to RNAi remains relatively untested. To test whether genes needed for RNAi defend animal cells against virus infection, we infected wild-type and RNAi-defective cells of the nematode C. elegans with vesicular stomatitis virus engineered to encode a GFP fusion protein. We show that upon infection, cells lacking components of the RNAi apparatus produce more GFP and infective particles than wild-type cells. Furthermore, we show that mutant cells with enhanced RNAi produce less GFP. Our observation that multiple genes required for RNAi are also required for resistance to vesicular stomatitis virus suggests that the RNAi machinery functions in resistance to viruses in nature.
RNA干扰(RNAi)是一种由外源性双链RNA触发的序列特异性基因沉默机制。在植物中,一种类似RNAi的机制可抵御病毒,但关于动物拥有与RNAi相关的类似天然抗病毒机制这一假说仍相对缺乏验证。为了测试RNAi所需的基因是否能保护动物细胞免受病毒感染,我们用经基因工程改造以编码绿色荧光蛋白(GFP)融合蛋白的水疱性口炎病毒感染线虫秀丽隐杆线虫的野生型和RNAi缺陷型细胞。我们发现,在感染后,缺乏RNAi装置组件的细胞比野生型细胞产生更多的GFP和感染性颗粒。此外,我们还表明,RNAi增强的突变细胞产生的GFP较少。我们观察到RNAi所需的多个基因对于抵抗水疱性口炎病毒也是必需的,这表明RNAi机制在自然界中对病毒的抗性中发挥作用。