PATHOGENESIS OF ALEUTIAN DISEASE VIRUS INFECTION

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The scope of this project is to elucidate pathogenic mechanisms involved in infections of mink with Aleutian mink disease parvovirus (ADV). In the past year we performed detailed studies on ADV infected adult mink using immunohistochemistry and strand specific in situ hybridization. lmmunohistochemistry was performed using antiserum specific for either virion or nonstructural proteins of ADV. Modifications to the in situ hybridization procedure increased the sensitivity between 10 and 100-fold, but due to the restricted nature of ADV replication in adult mink, combination immunohistochemistry and in situ hybridization was not possible. Immunohistochemical staining of mesenteric lymph node from adult mink 10 d after infection with ADV-Utah 1 localized ADV virion antigen in both the nuclei and cytoplasm of 2 types of cells. One had the morphology of macrophages located primarily along medullary cords and the other type resembled antigen presenting follicular dendritic cells (FDC) found within germinal centers. In situ hybridization revealed evidence of replication (mRNA and replicative form DNA) in cells having an identical distribution, however, it appeared that other macrophages and FDC contained virion DNA, but not replicative intermediates (mRNA and replicative form DNA). By 60 d after infection, however, active replication was noted only in macrophages. These results suggested that cells involved with phagocytosis and antigen presentation were targets for ADV replication throughout the course of infection. In addition, it was observed that 60 d after infection ADV replication was also occurring in renal tubular cells and glomeruli and that the replication correlated with glomerular pathology and desquamation of renal tubular cells. These studies suggested that mechanisms other than simple immune complex deposition may be involved in the genesis of the ADV renal disease.