Insect adaptive immunity

昆虫适应性免疫

基本信息

批准号：
10469408
负责人：
Raul Andino
金额：
$ 50.73万
依托单位：
UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-09-14 至 2024-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10469408
关键词：
Address Animal Model Antiviral Response Arboviruses Biogenesis Biological Assay Blood Circulation Cells Competence Complementary DNA Cultured Cells DNA amplification DNA biosynthesis DNA-Directed RNA Polymerase Data Defense Mechanisms Dengue Disease Distal Double-Stranded RNA Drosophila genus Drosophila melanogaster Face Generations Genetic Transcription Genome Goals Hemocytes Human Immune response Immune system Immunity Immunologic Memory Infection Insect Vectors Insecta Lead Mediating Medical Methods Nucleic Acids Organism Passive Immunization Pathogenicity Pathway interactions Physiology Process Production Proteomics RNA RNA Interference RNA chemical synthesis RNA-Directed DNA Polymerase Regulation Reverse Transcription Role Signal Transduction Site Small Interfering RNA Small RNA System Testing Tissues Transcript Vertebrates Vesicle Viral Virus Virus Diseases Virus Replication ZIKA adaptive immunity antiviral immunity base chikungunya design exosome fly functional genomics insight macrophage programs recruit response transmission process tripolyphosphate uptake vector viral DNA viral RNA

Address Animal Model Antiviral Response Arboviruses Biogenesis Biological Assay Blood Circulation Cells Competence Complementary DNA Cultured Cells DNA amplification DNA biosynthesis DNA-Directed RNA Polymerase Data Defense Mechanisms Dengue Disease Distal Double-Stranded RNA Drosophila genus Drosophila melanogaster Face Generations Genetic Transcription Genome Goals Hemocytes Human Immune response Immune system Immunity Immunologic Memory Infection Insect Vectors Insecta Lead Mediating Medical Methods Nucleic Acids Organism Passive Immunization Pathogenicity Pathway interactions Physiology Process Production Proteomics RNA RNA Interference RNA chemical synthesis RNA-Directed DNA Polymerase Regulation Reverse Transcription Role Signal Transduction Site Small Interfering RNA Small RNA System Testing Tissues Transcript Vertebrates Vesicle Viral Virus Virus Diseases Virus Replication ZIKA adaptive immunity antiviral immunity base chikungunya design exosome fly functional genomics insight macrophage programs recruit response transmission process tripolyphosphate uptake vector viral DNA viral RNA

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项目摘要

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.

概括该项目的核心目标是检查昆虫的抗病毒免疫。昆虫传播在全球引起宽度和使人衰弱的疾病。载体中的病毒复制和传播是传输能力的关键因素。 RNA干扰是绝缘的主要抗病毒系统在整个抑制组织中抑制病毒复制和病毒传播。涉及的机制开发和有效的抗病毒免疫学知之甚少。我们提议研究模型有机体果蝇中的抗病毒免疫。我们发现了这一点免疫力涉及血细胞摄取病毒双链RNA，然后逆转录到生成病毒DNA（VDNA），可以通过从头合成siRNAS来扩增RNAi响应（次要VSRNA）。果蝇免疫的中心是巨噬细胞样细胞，血细胞，是通过产生5'-三磷酸化的次级VSRNA来负责抗病毒RNAi扩增。在效应器面，VSRNA被掺入外泌体样蔬菜（ELVS）中。血细胞衍生的麋鹿介导将抗病毒VSRNA递送到未感染的组织中，并保护果蝇免受盘中部位的感染。在平行于脊椎动物的引人注目的情况下，苍蝇还依靠全身免疫来控制病毒感染，尽管这是病毒特异性信号是基于核酸的。我们假设血细胞从感染的细胞指导VDNA的合成，而VDNA的合成又次要VSRNA提供适应性免疫。我们将检查（i）VDNA合成的机制，（ii）VSRNA的生产和调节产生和（iii）抗病毒肘部的产生及其在抗病毒免疫中的功能。