Immunophenotypic study of atypical lymphocytes generated in peripheral blood and spleen of nude mice after MHV-72 infection

Inbred athymic nude mice (BALB/c) were injected subcutaneously with the wil d-type murine gammaherpesvirus 72 (MHV-72), which has been shown to induce the infectious mononucleosis (IM)-like syndrome in immunocompetent mice. Th e mice were also injected with UV-irradiated MHV-72. We studied the pattern of acute and chronic infection in the blood cells of the nude mice and det ected viral DNA sequences in the infected leukocytes by polymerase chain re action (PCR) technique up to when the animal died, close to 1 month postinf ection. Using the UV-irradiated virus that induces an increase in mouse sur vival time, the viral sequences were present in the blood up to 3 months po stinfection, then disappeared. We detected atypical lymphocytes in the bloo d of mice infected with both wt and UV-irradiated viruses. These atypical c ells were similar in shape to those present in the blood of patients with I M induced by Epstein-Barr virus (EBV). Via Unscheduled DNA Synthesis (UDS), DNA synthesis tvas demonstrated in the atypical cells whose phenotype is i dentical to that of B cells, as shown with a panel of monoclonal antibodies . By double immunofluorescence staining, using;an hyperimmune anti-MHV-72 s erum and an anti-IgG + IgM + IgA monoclonal antibody, we demonstrated that these atypical B cells express some viral antigens. Contrary to the immunoc ompetent mice, the nude mice did not develop splenomegaly after infection w ith wt virus, probably due to the lack of T cell subsets. However, we obser ved an increase of nude mice B cells in the spleen. The nude mice died 1 mo nth postinfection showing a high frequency (40%) of atypical lymphoblast-li ke B-cells in the blood; the increase in natural killer (NK) cell number wa s not detected after infection. Such findings suggest that NK cells probabl y did not play an important role in immune response to the MHV infection in nude mice. Finally, this mouse model could play an important role in antig ammaherpesviral therapy of immunocompromised patients.