Canine parvovirus, feline panleukopenia virus and mink enteritis virus form a group of closely related parvoviruses that differ genetically, antigenically, pathogenetically and in host range. Laboratory derived variants that differ antigenically (after selection with monoclonal antibodies), in host range (after selection in alternate host cell cultures) and in pathogenicity and plaque type (after prolonged passage in tissue culture) have been produced and are available for the proposed study. These naturally occurring and artificially selected variants would be used to ascertain relationships between viral structure and pathogenesis using a variety of proven methods. Biochemical studies of viral structure would include monoclonal antibody analysis, peptide mapping and isoelectric focusing, to define and compare the virus capsid proteins. The DNA of the individual viruses and variants would be analyzed and compared using restriction enzyme methods. Infections of dogs and cats and their cultured cells would be used to define host range differences between the prototype strains of canine parvovirus, feline panleukopenia virus, mink enteritis virus and their natural and laboratory-derived variants. The mechanisms of host range restriction would be define using biochemical methods to examine differences in the replication cycle of each virus in cells from alternate hosts. During the experimental infections of animals, further information would be derived on differences in the tropism of each virus for different lymphoid cells of the natural host. Variation at this level may explain reported differences in the clinical syndrome caused by each virus and may further define differences in the ability of the attenuated CPV and its virulent parental virus to cause disease. A further aspect of the study would involve the analysis of isolates of the viruses that have been collected over a 30-year period. The object would be to determine whether antigenic shift or variation has occurred and particularly whether variation could account for recent epizootics. The long term objective would include definition of the mechanisms by which these small, simple viruses vary in host range, pathogenicity, antigenic type and virulence. The variation would be define in terms of changes in virus structure, replication cycle and/or genome.
