Dept of Pathology, Microbiology and Immunology, University of South Carolina School of Medicine, Columbia, SC 29209, United States.
Virus Res. 2011 Jan;155(1):1-9. doi: 10.1016/j.virusres.2010.10.003. Epub 2010 Oct 14.
Pathogenic viruses have developed a molecular defense arsenal for their survival by counteracting the host anti-viral system known as RNA interference (RNAi). Cellular RNAi, in addition to regulating gene expression through microRNAs, also serves as a barrier against invasive foreign nucleic acids. RNAi is conserved across the biological species, including plants, animals and invertebrates. Viruses in turn, have evolved mechanisms that can counteract this anti-viral defense of the host. Recent studies of mammalian viruses exhibiting RNA silencing suppressor (RSS) activity have further advanced our understanding of RNAi in terms of host-virus interactions. Viral proteins and non-coding viral RNAs can inhibit the RNAi (miRNA/siRNA) pathway through different mechanisms. Mammalian viruses having dsRNA-binding regions and GW/WG motifs appear to have a high chance of conferring RSS activity. Although, RSSs of plant and invertebrate viruses have been well characterized, mammalian viral RSSs still need in-depth investigations to present the concrete evidences supporting their RNAi ablation characteristics. The information presented in this review together with any perspective research should help to predict and identify the RSS activity-endowed new viral proteins that could be the potential targets for designing novel anti-viral therapeutics.
病原体病毒通过对抗宿主抗病毒系统(即 RNA 干扰 (RNAi))来生存,从而开发了分子防御武器库。细胞 RNAi 除了通过 microRNAs 调节基因表达外,还作为抵御入侵性外源核酸的屏障。RNAi 在包括植物、动物和无脊椎动物在内的生物物种中都得到了保守。反过来,病毒也进化出了可以对抗宿主这种抗病毒防御的机制。最近对表现出 RNA 沉默抑制(RSS)活性的哺乳动物病毒的研究进一步加深了我们对宿主-病毒相互作用中 RNAi 的理解。病毒蛋白和非编码病毒 RNA 可以通过不同的机制抑制 RNAi(miRNA/siRNA)途径。具有 dsRNA 结合区域和 GW/WG 基序的哺乳动物病毒似乎具有很高的 RSS 活性赋予可能性。尽管植物和无脊椎动物病毒的 RSS 已经得到了很好的描述,但哺乳动物病毒的 RSS 仍需要深入研究,以提供支持其 RNAi 缺失特性的具体证据。本文综述中提供的信息以及任何前瞻性研究都应该有助于预测和识别具有 RSS 活性的新病毒蛋白,这些蛋白可能成为设计新型抗病毒治疗药物的潜在靶点。