Persistent infection of mink with Aleutian mink disease parvovirus (ADV) leads to progressive immune disorder characterized by high levels of antiviral antibodies, hypergammaglobulinemia, plasmacytosis, and immune complex disease. Virus is not neutralized in vivo and ADV exists in infectious immune complexes. Isolates of ADV differ markedly in their ability to induce AD. A major goal of this project is to correlate specific DNA sequences of the ADV genome to functional correlates, such as pathogenicity determinants and strain variation. A second goal is to characterize an ADV-binding protein (ABP)on the surface of susceptible cells that specifically binds ADV capsids and is th putative cellular receptor. A third major goal is to study the actual structure of the ADV virion. Understanding of the structure at high resolution will enable us to (a) map epitopes and pathogenicity determinants to discreet coordinates on the viral particle, (b) relate structural features to the unique biology of ADV in vivo. In the past year, work on this project led to a number of findings. N-terminal sequencing of ABP revealed an amino acid motif common to beta-tubulin like proteins. By studying additional chimeric and site-directed mutant ADV, we found that the expression of pathogenicity requires cooperative interactions of non-adjacent capsid protein amino acids. A neutralizing epitope has been mapped to the shoulder of the protrusions vicinal to the 3-fold axes of symmetry, and this epitope overlaps with a sequence mediating antibody-dependent enhancement (ADE) of infection. An additional and distinct sequence mediating ADE maps to amino acid residues contributing to the protrusions proper.