Arthropods represent the largest animal biomass on earth, including an enormous number of species that cause serious agricultural losses. Arthropods also vector important diseases of plants and animals. Arthropod populations are regulated by many viral diseases. In most interactions between insects and viruses, the virus enters the insect by the oral route and must move across the cells of the gut in order to access the blood and other tissues. Although critical in the virus-insect interaction, little is known about the mechanisms mediating viral trafficking through insect midgut cells. In this project, the investigators will examine the mechanisms of polarized viral transit through the epithelial cells of the insect midgut. This project aims to identify and characterize insect midgut proteins that mediate this process, and the viral protein signals that direct the process. The project will use an innovative experimental design that leverages the power of a Drosophila genetic system, combined with mutagenesis and analysis of model virus envelope proteins, baculovirus GP64 and VSV G. An understanding of the viral signals and the interacting midgut cell proteins and pathways that regulate or restrict virus trafficking through midgut cells can be used to both enhance infection by beneficial viruses (such as those used for biocontrol of insects), and to inhibit viral transmission in insect vectors of plant and animal diseases. Thus, the project should have impacts across a wide variety of virus-insect interactions and with applications in diverse areas such as agricultural crop protection, forestry, and animal and human health. The project includes active participation of a postdoctoral trainee and undergraduate students, and will also engage the public through open-house presentations to local elementary school children, and through presentations to high school teachers and their students.