Antiviral immunity directed by virus-derived small silencing RNAs in mice

描述（由申请人提供）：具有RNA基因组的病毒是重要的人类病原体，具有与DNA病毒不同的遗传和免疫学特性。植物和无脊椎动物宿主产生长度为21-24个核苷酸的病毒衍生小干扰RNA (sirna)，以指导RNA干扰（RNAi）特异性清除RNA病毒。然而，目前尚不清楚保守的RNAi途径是否在哺乳动物中具有类似的抗病毒作用。本文和首席研究员最近在《科学》杂志上发表的两篇论文中描述的新发现为诱导抗病毒RNAi和特异性灭菌免疫提供了证据

DESCRIPTION (provided by applicant): Viruses with an RNA genome are important human pathogens and exhibit distinct genetic and immunological properties from DNA viruses. Plant and invertebrate hosts produce virus-derived small interfering RNAs (siRNAs) of 21-24 nucleotides in length to guide specific clearance of RNA viruses by RNA interference (RNAi). However, it has been unclear if the conserved RNAi pathway has a similar antiviral role in mammals. New findings described here and in two recent papers in Science by the principal investigator provide evidence for the induction of antiviral RNAi and specific sterilizing immunity in mice by a mosquito-transmissible positive-strand RNA virus. Preliminary studies also indicate a role for the viral suppression of RNAi in mouse infection and for a known innate immune sensor of RNA viruses in the biogenesis of the predominantly 22- nucleotide viral siRNAs. Using the established mouse model, a complementary set of studies is proposed to characterize the function and mechanism of the mammalian RNAi- mediated antiviral immunity. Moreover, possible regulatory roles of interferon signaling and the interferon-stimulated innate immune sensors of RNA viruses in the new form of mammalian antiviral immunity will be examined. These studies will likely open up a new area of research on the antiviral immunity mechanisms in mammals.