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; some like ADV-Utah and ADV-TR are highly pathogenic in vivo, but are replication defective for CRFK cells. The cell-culture ADV-G is replication competent for CRFK, but replicates poorly, if at all, in mink and does not cause progressive disease. 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. Another 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 number of findings. A method was developed to purify ABP, the putative cellular receptor for ADV from CRFK cells; an antibody against ABP was developed. Initial attempts at N-terminal sequencing were unsuccessful, possibly due to a blocked N- terminus. By studying viruses chimeric between ADV-G and ADV-Utah, we identified capsid protein residues that regulate in vivo and in vitro replication. One chimeric virus, H534D, replicated in vivo and induced a novel hepatocellular lesion that resembled Reye?s syndrome. - Parvoviruses, Aleutian mink disease parvovirus, virus structure, viral pathogenesis, host range, virus receptors
