Suppression of the Insect Cellular Immune Response by a Polydnavirus

了解病原体如何在动物和植物中引起疾病对基础生物学，农业和医学至关重要。 其中最致命的昆虫病原体是与寄生蜂相关的共生多脱氧核糖核酸病毒（PDV）。 PDV不在寄生虫的宿主昆虫中复制，但不同病毒基因产物的表达引起严重的疾病症状，包括免疫系统抑制。估计有40，000种寄生虫携带PDV，并攻击地球上几乎所有重要的害虫。 由于每个PDV-寄生蜂协会是遗传上独特的，PDV代表了具有不同应用的毒力分子的巨大储存库。 开发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。 该提案的目标是表征PDV Microplitis demolitor bracovirus（MdBV）如何破坏两种关键的细胞免疫反应，即包囊和吞噬作用。 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）鉴定MdBV使之失能的宿主分子，以及3）表征MdBV如何全面改变宿主昆虫免疫活性。 这项研究的结果有可能提供有关病毒如何免疫抑制昆虫和其他动物的基本新信息。 该研究也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、研究生和本科生学员提供独立研究的机会。 这项研究的结果也将用于加强高中、本科和研究生阶段的课堂教学。

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.