Picornaviruses are associated with a diversity of diseases in man and animals. In recent years compelling evidence has accumulated indicating that at least some of these conditions have an autoimmune pathogenesis. Since picornaviruses are generally believed to lyse cells during replication, the mechanism of host sensitization has proven an enigma. The research in this program will address this specific issue in using three well characterized models of human disease (myocarditis and congestive myocardopathy, demyelinating encephalomyelitis, and Type I diabetes mellitus)-induced with a single agent, the encephalomyocarditis virus (EMC). The focus of this research will be pathogenesis, but the tools are immunological and pathological. Because genetics proves to be a key element in these diseases, considerable emphasis will focus on the heritable influences affecting their development in animals. The program is organized into four individual research projects with four supporting cores. Project I is concerned with the basic mechanism of auto- sensitization by virus altered cells. Project II addresses the genetics of EMC induced demyelinating disease and will explore pathogenic mechanisms involving T cell clones and their receptors. Project III examines the pathogenesis of myocarditis comparatively using the well characterized Coxsackievirus Group B-3 model and the cardiotropic strain of EMC virus. Project IV explores the immunological mechanism of diabetes in various strains of mice, many of which develop diabetes having differing "clinical" characteristics. The cores provide coordinated, cost effective services, consultation and the sharing of reagents. Core A is for administration. Core B provides animals from breeding stocks, and will custom breed strains and crosses. In addition, infected animals will be managed and monitored by the staff, thus, standardizing data accumulation and reducing variables. Core C will develop immunological resources such as T cell clones and monoclonal antibody for use in the various projects and will conduct commonly used assays. Core D carries out routine and immunological histochemical procedures using light and electron microscopy as well as morphometry.