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.