The long term goal of this project is to define the mechanisms by which viruses evade or suppress the immune response and establish a persistent infection in the mammalian host. Aleutian disease is an economically important persistent infection of mink and ferrets caused by an autonomous parvovirus. Lesions in Aleutian disease are caused by immune complexes, and can be prevented by immunosuppression. Certain virus-host combinations result in an unrestrained humoral immune response to viral proteins. Aleutian disease is a good model for studying the interaction between a virus and the host immune system, and the disease has similarities to human rheumatologic disease. The unrestrained humoral immune response to viral proteins in Aleutian disease may be caused by infection of T suppressor lymphocytes, followed by death or inactivation of these cells. The types of lymphocytes infected in vivo will be assessed by immunofluorescence and immunoenzyme staining of separated lymphocyte populations. The tropism of Aleutian disease virus for differentiating lymphocytes will be studied by in vitro infection of separated lymphocyte populations. Since Aleutian disease virus is processed in vivo by proteolytic enzymes, an experiment to determine if new antigens are exposed by the proteolytic cleavage will be done.