The long term objectives of the research outlined in this proposal are to identify and characterize the mechanisms by which baculoviruses replicate their DNA. Baculoviruses have been exploited for the production of foreign gene products which are not only highly expressed, but are also processed in a manner equivalent to higher eukaryotes and consequently are often biologically active. Therefore, they have found applications in a variety of research programs such as experimental human and animal vaccine development, experimental therapeutic agents, and for fundamental biomedical research. Despite their widespread use, little is known about the mechanisms by which they replicate their DNA. The research outlined in this proposal will focus on the role of the viral and host cell DNA polymerase in baculovirus genome replication, the viral replicative intermediates will be characterized, the interaction and location in the cell of gene products implicated in DNA replication will be investigated and the characterization of the roles of factors likely involved in genome processing. From these studies, major advances in the elucidation of this important and possibly novel replication system are expected.
