Suppression of the Insect Cellular Immune Response by a Polydnavirus

了解病原体如何在动植物中引起疾病对基础生物学、农业和医学至关重要。昆虫中最致命的病原体是与寄生蜂相关的共生多dna病毒（pdv）。pdv在寄主昆虫中不复制，但不同病毒基因产物的表达会引起严重的疾病症状，包括免疫系统的抑制。据估计，有4万种拟寄生虫携带pdv，几乎可以攻击地球上所有重要的害虫。由于每一种pdv -寄生性关联在遗传上都是独特的，因此pdv代表了具有不同应用的毒力分子的巨大储存库。利用这一资源的关键需求是PDV基因组的表征和特定基因的功能研究。本提案的目的是表征PDV微炎拆除者臂状病毒（MdBV）如何破坏两个关键的细胞免疫反应，称为包封和吞噬。具体目标是：1)表征MdBV产生的破坏宿主细胞防御的毒力分子的结构，2)识别MdBV禁用的宿主分子，以及3)表征MdBV如何在全球范围内改变宿主昆虫的免疫活性。这项研究的结果有可能提供关于病毒如何免疫抑制昆虫和其他动物的基本新信息。拟议的研究还为促进科学培训和教育提供了一个理想的平台。该项目将为免疫学、病毒学和寄生虫学的博士后、研究生和本科生提供独立的研究机会。研究结果还将用于提高高中、本科和研究生水平的课堂教学。

Understanding how pathogens cause disease in animals and plants is critically important to basic biology, agriculture, and medicine. Among the most virulent pathogens of insects are symbiotic polydnaviruses (PDVs) associated with parasitoid wasps. PDVs do not replicate in the host insects of the parasitoid but expression of different viral gene products cause severe disease symptoms including suppression of the immune system. An estimated 40,000 species of parasitoids carry PDVs and attack almost every significant pest insect on earth. Since each PDV-parasitoid association is genetically unique, PDVs represent a vast repository of virulence molecules with diverse applications. Key needs for tapping this resource is characterization of PDV genomes and functional studies of specific genes. The goal of this proposal is to characterize how the PDV Microplitis demolitor bracovirus (MdBV) disrupts two key cellular immune responses called encapsulation and phagocytosis. Specific objectives are to: 1) characterize the structure of the virulence molecules MdBV produces to disrupt host cellular defenses, 2) identify the host molecules that MdBV disables, and 3) characterize how MdBV globally alters host insect immune activity. Results of the study have the potential to provide fundamental new information on how viruses immunosuppress insects and other animals. The proposed research also provides an ideal platform for promoting both scientific training and education. The project will provide independent research opportunities for postdoctoral, graduate and undergraduate trainees in immunology, virology and parasitology. Results from the study will also be used to enhance classroom instruction at the high school, undergraduate, and graduate levels.