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 continued studies on the replication of ADV in macrophages. Expression and replication of the ADV genome was examined in primary peritoneal macrophage cultures derived from adult mink. A small percentage of macrophages infected with the pathogenic ADV-Utah 1, but not the cell culture adapted ADV-G, expressed ADV antigens following infection. Analysis of DNA prepared from ADV-Utah 1 infected macrophages revealed definite amplification of the ADV genome and the presence of ADV DNA replicative forms (RF), but the level of gene expression was too low to allow the definition of specific viral proteins by Western blot. Several human monocyte cell lines (U-937 and THP-1) were also found to support ADV-Utah 1 expression and the expression could be modulated by treatment with an inducer of macrophage differentiation. Virus could not be serially propagated in U-937 cells, thus the infection was not fully permissive, but was restricted as is seen in vivo infections. The various replicative forms of ADV DNA were present, but the relative level of single stranded virion DNA appeared to be lower than in permissively infected cells. The 2 capsid proteins and the major nonstructural protein, NS-1, were present in infected U937 cells. The three size classes of viral mRNA were observed, but the 2.8 kb mRNA band in these cells could be resolved into 2 definite components, slightly different from permissively infected cells. This finding might reflect a variation in the expression of the smaller NS-2 protein between permissive and restricted ADV infections. Mink lymph node cultures were found to express a bioactive IL-6, but the gene for mink IL-6 has not yet been cloned. In addition, U937 cells infected with ADV-Utah 1, but not ADV-G, elaborate human IL-6.
