Genetic Analysis of the Drosophila Response to Viral Infection

果蝇对病毒感染反应的遗传分析

• 批准号: 7202833
• 负责人: JULES A HOFFMAN
• 金额: $ 41.59万
• 依托单位: SCRIPPS RESEARCH INSTITUTE, THE
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-05-01 至 2011-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7202833
• 关键词: DNA virus; Drosophilidae; Picornaviridae; RNA virus; Sindbis virus; arthropod genetics; cell line; gene mutation; genetic markers; genetic screening; genetic susceptibility; genetic transcription; genetically modified animals; green fluorescent proteins; host organism interaction; immune response; immunogenetics; microarray technology; microorganism immunology; phenotype; recombinant proteins; reporter genes; virus RNA; virus diseases; virus protein

The objective of this project is to analyze host defense mechanisms against viral infection in the model organism Drosophila melanogaster, and to do so in the light of concurrent studies of viral infection in mice, carried out by our colleagues in La Jolla and in Osaka. Like all other organisms, insects are afflicted by viruses and react to viral infections. We posit that by studying the response of Drosophila to viral infection we will uncover evolutionary conserved mechanisms of innate immunity that, together with the programs developed in the other participating laboratories, will help to unravel the essential aspects of the antiviral response in mammals. The project has three specific aims. The first two aims are based on our studies of the global transcriptional response to infection by two RNA viruses. The genes induced by virus infection will be used as markers in forward genetic screens to identify mutations that impair the antiviral response (Specific Aim 1). Moreover, interesting candidate antiviral effector molecules will be selected from the list of genes induced by viral infection, and functionally characterized (Specific Aim 2). The third aim is to provide an extended view of the complete repertoire of responses to virus infection in Drosophila, using microarrays to compare the response to infection in different tissues, to investigate the response to different types of viruses (in particular DMA viruses), and finally, to analyze the response to viral RNA and viral proteins. The relevance of this research to public health will be three-fold. First, characterization of the pristine host defense against viral infection in Drosophila may reveal novel evolutionary conserved pathways of host defense in mammals, as occurred in the case of Toll-like receptors. Second, the Drosophila model may reveal original strategies to counter viral infection that may guide the development of antiviral therapeutics. Third, emerging viral diseases with global impact, such as West Nile virus infection, are transmitted by Aedes mosquitoes, which, like Drosophila, belong to the order Diptera. Our research may shed light on the interaction between arthropod-borne viruses and their insect vectors.

该项目的目的是在模型中分析宿主针对病毒感染的防御机制 黑腹果蝇，并根据小鼠病毒感染的同时研究， 由我们在拉霍亚和大阪的同事进行。与所有其他生物一样，昆虫也受到以下疾病的困扰 病毒并对病毒感染做出反应。我们假设，通过研究果蝇对病毒感染的反应，我们 将揭示先天免疫的进化保守机制，连同程序 其他参与实验室开发的，将有助于揭示抗病毒药物的基本方面 哺乳动物的反应。该项目有三个具体目标。前两个目标基于我们的研究 对两种 RNA 病毒感染的整体转录反应。病毒感染诱导的基因会 用作正向遗传筛选的标记，以识别损害抗病毒反应的突变 （具体目标1）。此外，有趣的候选抗病毒效应分子将从以下列表中选出： 病毒感染诱导的基因，并进行功能表征（具体目标 2）。第三个目标是提供 使用微阵列对果蝇病毒感染反应的完整库进行扩展 比较不同组织对感染的反应，研究对不同类型感染的反应 病毒（特别是 DMA 病毒），最后分析对病毒 RNA 和病毒蛋白的反应。这 这项研究与公共卫生的相关性有三重。一、原始宿主的表征 果蝇防御病毒感染可能揭示宿主新的进化保守途径 哺乳动物的防御，就像 Toll 样受体的情况一样。其次，果蝇模型可以 揭示对抗病毒感染的原始策略，可能指导抗病毒疗法的开发。 第三，具有全球影响的新出现的病毒性疾病，例如西尼罗河病毒感染，是通过以下途径传播的： 伊蚊，与果蝇一样，属于双翅目。我们的研究可能会揭示 节肢动物传播的病毒与其昆虫媒介之间的相互作用。