Increased Neoplasm Development Due to Immunosuppressive Treatment with FK-506 in BALB/C Mice Persistently Infected with the Mouse Herpesvirus (MHV-72)

BALB/c mice were infected with the lymphotropic mouse gammaherpesvirus (MHV-72). At late (7–12 months) post-infection intervals the latent virus was detected in the cells of lymphatic system (peripheral blood, lymhocytes and macrophages, thymocytes, lymph nodes, bone marrow, and peritoneal macrophages,) and in the spleen, lungs, liver, and kidney by cocultivation as well as by explantation. The MHV-72 infected mice, in which latency had been established, were treated with the immunossuppressive (IS) drug FK-506 (2 mg/kg/mouse for 30 days). This treatment increased the probability of virus reactivation by over two-fold. During the post-treatment observation period of 19 months, the incidence of lymphomas and the development of MHV-related lymphoproliferative and hemoblastic disorders rised to nearly five-fold in the drug treated mice as compared to untreated animals.