We propose to establish the relationship between the structural polypeptides of picornaviruses and the antigenicity of the intact virion by a combination of surface labeling and proteolytic enzyme treatment. Poliovirus and rhinovirus proteins will be studied by counter- immunoelectrophoresis, radioimmunoassay, isoelectric focusing, and peptide mapping to determine which proteins contribute to the serological cross-reactions, especially in rhinoviruses. Comparisons between wild and attenuated strains of poliovirus will also be done using these methods to determine which of the 4 structural proteins are responsible for virulence and antigenicity. The specificity of human sera will be examined to establish which antigens and subcomponents or polypeptides are recognized in natural human infections of rhinovirus and poliovirus. The immune response to virus and the mechanism of viral antigen processing will be studied in rabbits and mice by sequential immunization with virus followed by individual polypeptides or using single polypeptides as primary immunogen followed by intact virus. Antibody response will be measured by neutralization, radioimmunoassay and counter-electrophoresis. Lymphocytes from primary immunized animals will be challenged in vitro with virus or individual virus protein. In addition, heterologous stimulation of lymphocytes by serologically related rhinoviruses will provide information on heterotypic immune response in rhinoviruses. Finally, the role of B and T lymphocytes in viral antigen recognition, antigen processing, and heterotypic virus stimulation will be studied.