Comparison of early splenic changes associated with replication of viruses in murine monocytic macrophages

An effect of replication of certain viruses in murine monocytic macrophages was manifested by depletion of cells through degenerative and necrotizing changes in thymus-dependent areas of lymphoid structures. In mice infected with murine hepatitis virus (MHV-3) or lactate dehydrogenase virus, these changes were transient in mice killed on postinoculation day (PID) 2. To study these morphologic changes due to viral replication, adult Swiss specific-pathogen-free homozygous nude mice (nu/nu) and their heterozygous haired littermates (nu/+) were inoculated with 10(5) LD50 of MHV-3, euthanatized, and necropsied on PID 1, 2, 4, 6, 8, and 10 along with noninoculated controls. The nu/+ and nu/nu mice killed on PID 2 had lymphocytic karyorrhexis and depletion of cells in the thymus-dependent area. In the heterozygote, these characteristic lesions were transient; whereas in the homozygote, lesions persisted and were present in survivors euthanatized and necropsied on PID 16. Although the intensity of lesions due to MHV-3 varied between nu/+ and nu/nu mice, virus titers determined on liver homogenates were similar for the homozygote and heterozygote during acute disease. Nude and nonnude mice given lactate dehydrogenase virus and killed on PID 2 had a transient depletion of lymphocytes; whereas mice given lymphocytic choriomeningitis virus and killed on PID 4 had a similar lesion. Lesions neither occurred when mice were treated with silica before inoculation, indicating that functional monocytic macrophages were required, nor occurred when another virus, herpes simplex virus type 1, was given.