T cell ignorance in mice to Borna disease virus can be overcome by peripheral expression of the viral nucleoprotein

Infection of neonates with Borna disease virus (BDV) induces severe meningo encephalitis and neurological disorder in wild-type but not in beta(2)-micr oglobulin-deficient mice of strain MRL (H-2(k)). Temporary in vivo depletio n of CD8(+) T cells delayed BDV-induced disease for several weeks. Depletio n of CD4(+) T cells had a similar beneficial effect, indicating that the BD V-induced neurological disorder in mice is a CD4(+) T cell-dependent immuno pathological process that is mediated by CD8(+) T cells. Lymphocytes prepa red from brains of diseased mice were mainly from the CD8(+) T cell subset. They showed up regulation of activation markers and exerted strong MHC I-r estricted cytotoxic activity against target cells expressing the BDV nucleo protein p40, Infection of B10.BR (H-2(k)) or congenic C57BL/10 (H-2(b)) mic e resulted in symptomless, lifelong persistence of BDV in the brain. Superi nfection with a recombinant vaccinia virus expressing BDV p40 but not with other vaccinia viruses induced severe neurological disease and encephalitis in persistently infected B10.BR mice but not in persistently infected C57B L/10 mice, indicating that the disease-inducing T cell response is restrict ed to the nucleoprotein of BDV in H-2(k) mice, Our results demonstrate that the cellular arm of the immune system may ignore the presence of a replica ting virus in the central nervous system until proper antigenic stimulation at a peripheral site triggers the antiviral response.