Insect adaptive immunity

摘要 该项目的中心目标是检查昆虫的抗病毒免疫能力。虫媒病毒的昆虫传播 在全球范围内引起广泛的、令人衰弱的疾病。病毒在载体中的复制和传播 是传播能力的关键因素。RNA干扰是昆虫主要的抗病毒系统 抑制病毒复制和病毒在昆虫组织中的传播。涉及到的机制 人们对发展和有效的抗病毒免疫知之甚少。 我们建议在模式生物黑腹果蝇中研究抗病毒免疫。我们发现 免疫包括血细胞摄取病毒双链RNA，然后逆转录至 产生病毒DNA(VDNA)，通过从头合成siRNAs来放大RNAi反应 (辅助vsRNAs)。果蝇免疫的中心是巨噬细胞样细胞，即血细胞，它们是 负责通过生产5‘-三磷酸化的二级vsRNAs进行抗病毒RNAi扩增。在 在效应器表面，vsRNA被整合到外体样囊泡(ELV)中。血细胞来源的ELV介导 将抗病毒vsRNA运送到未受感染的组织，并保护苍蝇免受远端部位的感染。 与脊椎动物惊人的相似之处是，苍蝇也依靠系统免疫来控制病毒感染，尽管在这方面 病毒特异性信号以核酸为基础。我们假设血细胞从 感染细胞指导VDNA的合成，进而模板辅助vsRNA提供适应性 豁免权。我们将研究(I)vDNA合成的机制，(Ii)vsRNA的产生和调节 (3)抗病毒ELV的产生及其在抗病毒免疫中的作用。

SUMMARY The central goal of this project is to examine antiviral immunity in insects. Insect transmission of arboviruses causes widespread and debilitating disease across the globe. Viral replication and dissemination in the vector are critical factors in transmission competence. RNA interference is the insect major antiviral system that inhibits viral replication and viral dissemination throughout the insect tissues. The mechanisms involved in developing and effective antiviral immunity are poorly understood. We propose to study antiviral immunity in the model organism Drosophila melanogaster. We discovered that immunity involves uptake of viral double stranded RNA by hemocytes, followed by reverse transcription to generate viral DNAs (vDNAs) that enables amplification of the RNAi response by de novo synthesis of siRNAs (secondary vsRNAs). Central to Drosophila immunity are macrophage-like cells, hemocytes, which are responsible for antiviral RNAi amplification by the production of 5’-triphosphorylated secondary vsRNAs. In the effector face, vsRNAs are incorporated into exosome-like vesicles (ELVs). Haemocyte-derived ELVs mediate the delivery of antiviral vsRNAs to uninfected tissues and protect flies from infection at distal sites. In striking parallel to vertebrates, flies also rely on systemic immunity to control viral infection, albeit in this case the virus-specific signal is nucleic acid-based. We hypothesize that haemocytes take up dsRNA from infected cells to direct the synthesis of vDNA, which in turn templates secondary vsRNA providing adaptive immunity. We will examine (i) the mechanisms of vDNA synthesis, (ii) production and regulation of vsRNA production and (iii) the generation of antiviral ELVs and their function in antiviral immunity.