CD8

A recently described mouse homolog of the human roseoloviruses, murine roseolovirus (MRV), causes loss of peripheral and thymic CD4+ cells during neonatal infection of BALB/c mice. Despite significant disruptions to the normal adaptive immune response, infected BALB/c mice reproducibly recover from infection, consistent with prior studies on a related virus, mouse thymic virus (MTV). Herein we show that in contrast to published studies on MTV, MRV appears to robustly infect neonatal C57BL/6 (B6) mice causing severe depletion of thymocytes and peripheral T-cells. Moreover, B6 mice recovered from infection. We investigated the mechanism of thymocyte and T-cell loss, determining that the major thymocyte subsets were infected with MRV, however CD4+ and CD4+CD8− showed increased apoptosis during infection. We found that CD8+ T-cells populated MRV-infected thymi. These CD8+ T cells expressed markers of activation, had restricted T-cell receptor repertoire and accumulated intracellular effector proteins, consistent with a cytotoxic lymphocyte phenotype, and suggesting their involvement in viral clearance. Indeed, absence of CD8+ T-cells prevented recovery from MRV infection and led to lethality in infected animals whereas B-cell deficient mice showed CD4+ T-cell loss but recovered from infection without lethality. Thus these results demonstrate that CD8+ T-cells are required for protective immunity against a naturally occurring murine pathogen that infects the thymus, and establish a novel infection model for MRV in B6 mice, providing the foundation for detailed future studies on MRV with the availability of innumerable mutant mice on the B6 background.