Determining the mechanism of Wolbachia pathogen blocking

确定沃尔巴克氏体病原体阻断机制

• 批准号: 9242754
• 负责人: Irene Newton
• 金额: $ 19.01万
• 依托单位: TRUSTEES OF INDIANA UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-12-01 至 2018-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9242754
• 关键词: Aedes; Affect; Alphaproteobacteria; Arboviruses; Area; Arthropod Vectors; Arthropods; Bacteria; Biological Models; Cell Line; Chromosomes; Culicidae; Data; Databases; Dengue Virus; Disease; Disease Vectors; Drosophila genus; Drosophila melanogaster; Gene Expression; Genetic; Genetic Determinism; Genomics; Goals; Haploidy; Host resistance; Human; Infection; Insect Vectors; Insect Viruses; Insecta; Interruption; Microbe; Microscopy; Neighborhoods; Parasites; Pathway interactions; Phenotype; Planets; Prevention; Production; Public Health; Quantitative Reverse Transcriptase PCR; RNA; RNA Interference; RNA Viruses; Resistance; Risk; Sindbis Virus; Source; Structural Protein; System; Temperature; Translating; Vaccines; Vector-transmitted infectious disease; Viral Genome; Viral Structural Proteins; Virion; Virus; Virus Diseases; Virus Replication; Virus-like particle; Wolbachia; Work; climate change; co-infection; design; disorder control; fly; high throughput analysis; innovation; knock-down; mutant; pathogen; phenotypic data; protein protein interaction; response; tool; transcriptomics; transmission process; vector; vector control; vector mosquito; viral transmission; virus host interaction

PROJECT ABSTRACT Vector-borne diseases affect millions of people worldwide and are becoming an increasing threat as the effects of climate change become more significant. Due to the rise in global temperatures, the likelihood of vector borne diseases will increase in many areas as the range of insects, such as mosquitos, expands and changes. Wolbachia are maternally transmitted bacteria that infect nearly half of the insect species on the planet and block the replication and transmission of several human pathogens within insect vectors (so called “pathogen blocking”). Wolbachia-infected mosquitos have been released in several parts of the world in order to control the transmission of Dengue virus. Importantly, the mechanism of pathogen blocking is not well understood. Unfortunately, our understanding of the Wolbachia-vector systems have been limited due to the lack of genetic tools in Wolbachia and the intractability of many important vectors. Our project is aimed at overcoming these obstacles by using the model system, Drosophila melanogaster, to identify genetic factors important for the interaction of Wolbachia with its host and SINV, an RNA virus. Our project uses the powerful genetic tools available in the fly to identify host components necessary for Wolbachia pathogen blocking. Our results will define the genetic interaction network for Wolbachia and key host pathways relevant to RNA virus replication, revealing mechanisms used by the bacterium to block pathogens, allowing for precise experimentation in non-model organisms, such as mosquito vectors. Our innovative approach will serve as a platform to mechanistically investigate the Wolbachia-insect- virus tripartite symbioses. The use of a model system allows us to leverage the power of Drosophila genetics to reveal mechanisms of interaction in a previously intractable intracellular symbiont. Results will be broadly relevant to other disease systems, as we will identify pathways and mechanisms for microbe-vector interaction.

项目摘要 媒介传播疾病影响着全世界数百万人，并且随着疾病的流行，其威胁日益严重 由于全球气温上升，气候变化的影响变得更加显着。 随着蚊子等昆虫范围的扩大，许多地区媒介传播疾病的数量将会增加 沃尔巴克氏体是母体传播的细菌，可感染近一半的昆虫物种。 地球并阻止昆虫媒介中几种人类病原体的复制和传播（因此 被称为“病原体阻断”）。 世界各国为了控制登革热病毒的传播，重要的是研究病原体的机制。 不幸的是，我们对沃尔巴克氏体载体系统的理解还不够深入。 由于缺乏沃尔巴克氏体遗传工具以及许多重要的难处理性，该研究受到了限制。 我们的项目旨在通过使用模型系统果蝇来克服这些障碍。 黑腹果蝇，以确定对沃尔巴克氏体与其宿主相互作用重要的遗传因素 SINV，一种RNA病毒。 我们的项目使用果蝇中可用的强大遗传工具来识别所需的宿主成分 我们的结果将定义沃尔巴克氏菌和沃尔巴克氏菌的遗传相互作用网络。 与 RNA 病毒复制相关的关键宿主途径，揭示了细菌用于复制的机制 阻止病原体，从而可以在非模型生物（例如蚊媒）中进行精确实验。 我们的创新方法将作为机械研究沃尔巴克氏体昆虫的平台 病毒三方共生体的使用使我们能够利用果蝇的力量。 遗传学揭示了先前棘手的细胞内共生体中的相互作用机制。 将与其他疾病系统广泛相关，因为我们将确定疾病的途径和机制 微生物-载体相互作用。