申请人在哺乳动物系统中发现并证明了RNA干扰介导的抗病毒免疫机制（Science，2013）。哺乳动物RNA干扰介导的抗病毒领域目前处于比较初期的阶段，之前还没有一个简单易行的研究系统来研究其作用机制，这大大滞后了该研究方向的快速发展。申请人通过多年在该研究领域的实践和积累，完善了利用RNA干扰抑制子缺陷病毒来研究哺乳动物如何利用RNA干扰来抵御病毒侵染的研究系统。哺乳动物中病毒特异性siRNA作为一种新发现的非编码RNA，是RNA干扰介导的抗病毒机制中的重要一环，对其生成、加工、修饰和代谢的生物学特征我们还知之甚少，该研究计划针对于这些核心问题进行了探讨；同时，进一步的研究将揭示这些特异性siRNA是如何被病毒编码的抑制子所抑制，这种不同抑制机理的阐明，可以帮助我们了解这种异性siRNA和其它重要生物分子间的相互作用关系，为研究人体免疫系统综合、协调地抵御病毒的侵染提供科学的依据。

My research is primarily dedicated to investigate the role and mechanism of antiviral RNA interference (RNAi) in mammals (Science 2013). In mammals, pathogen recognition receptors, their downstream signaling pathways and the induction of an interferon type I response that acts cell autonomously and cell nonautonomously have well-established roles in the antiviral response. In contrast, plants and invertebrates lack some or most of these pathways but rely instead on a highly efficient cell-autonomous machinery to fight against viral infections in the cytoplasm: RNAi. Plant and insect viruses have evolved diverse virulence proteins to suppress RNAi (VSR protein) because their hosts produce virus-derived small interfering RNAs (siRNAs) to direct specific antiviral defense by an RNAi mechanism dependent on the slicing activity of Argonaute proteins. . Our findings illustrate the importance of using VSR-deficient mutant viruses to probe antiviral RNAi and provide the first experimental system to characterize the viral siRNAs from naturally occurring precursors in mammalian cells. It also explains why previous attempts failed to detect significant levels of canonical vsiRNAs in wild type mammalian cells challenged by wild type viruses. The functional mechanism of viral siRNA in mammals are largely unknown. My study will discover the generating, processing and metabolic mechanism of viral siRNA in mammals. Discovery of mammalian antiviral RNAi provides a new framework to investigate the innate and adaptive control of important human viral pathogens.