9420638 Beckage The goal of this project is to determine how parasites exploit biochemical mechanisms of host interaction to achieve successful development in their host. Parasites suppress the immune system of the host, and escape being recognized as foreign. In the system under study, a wasp parasite (called a parasitoid) lays its eggs in the body cavity of its host, the tobacco hornworm, and the wasp develops to maturity and kills its host. Because parasitoids invariably invade their hosts, they are effectively exploited in the biological control of many devastating insect pests. The immunological interactions between parasitoids and hosts are important because they determine the host range of the parasitoid, and these physiological interactions are the focus of this study. Importantly, the parasitoid Cotesia congregata injects a large DNA virus (termed a polydnavirus) into the hemolymph of the host during parasitization and deposition of eggs into the hemocoel. The role of the virus is to suppress the host's immune response, much like the AIDS virus depresses the mammalian immune response making the host show enhanced susceptibility to other parasites and pathogens. The mechanisms of host immunosuppression, and their regulation by the virus, will be explored using a variety of biochemical and molecular techniques. Genetic selection techniques will be utilized to generate a "refractory" line of hosts which do not support development of the parasite, allowing us to clarify the biochemical mechanisms of resistance. The research provides an excellent framework for deciphering how parasites work to achieve successful infection of their host, and will provide data of fundamental importance to the fields of immunology, physiology, parasitology, virology, entomology, epidemiology, and evolutionary biology. ***