THEILERS VIRUS-INFECTION OF PERFORIN-DEFICIENT MICE

Theiler's virus, a murine picornavirus, infects the central nervous sy stems of C57BL/6 mice and is cleared after approximately 10 days by a process which requires CD8(+) cytotoxic T cells. We used perforin-defi cient C57BL/6 mice to test the role of this protein in viral clearance . Perforin-deficient mice died from viral encephalomyelitis between da ys 12 and 18 postinoculation. They had high levels of viral RNA in the ir central nervous systems until the time of death. In contrast, viral RNA had disappeared by day 11 postinoculation in wild-type C57BL/6 mi ce. Cytotoxic T cells can kill infected cells by two main mechanisms: the secretion of the pore-forming protein perforin or the interaction of the Fas ligand with the apoptosis-inducing Fas molecule on the targ et cell. Our results demonstrate that clearance of Theiler's virus fro m the central nervous system in C57BL/6 mice is perforin dependent.