The scope of this project is the study of infections of mink with the Aleutian mink disease parvovirus (ADV). In the past year we have extended the use of strand-specific in situ molecular hybridization to define sites of ADV replication and sequestration in experimentally infected adult mink. In infected adult mink, target cells for ADV replication could be found only in lymphoid organs. These cells (up to 2% of total) were located in the centers of germinal centers and scattered throughout the mesenteric lymph node cortex; a distribution suggestive of cells of the B-cell lineage. However, the amounts and ratios of replicative intermediates (RF DNA, mRNA and vDNA) in each infected cell dramatically differed from the permissive cell-virus systems we previously studied; the levels of all 3 were damped by at least a factor of 10 and the amount of RF was disproportionately decreased. These results have led us to conclude that infection in these target cells was being restricted by some mechanism. Furthermore, as infection progressed to a chronic state, cells replicating virus became undetectable, suggesting that the number was either extremely low (greater 1/105) or that the restriction was progressively more severe. A restriction on viral replication and transcription in ADV infected lymphoid cells might provide a mechanism for the development of immune disorders and for the maintenance of persistent infection. Large amounts of virions were sequestered in the periphery of germinal centers in a distribution very similar to that of processed antigen, possibly providing an explanation for the extreme antiviral antibody response observed in these animals. Antiviral antibody may be important in the development of persistent infection, because treatment of ADV infected mink kits with specific antibody converted the highly permissive infection of the alveolar type II cells into a restrictive one similar to that described above.
