BORNA-DISEASE VIRUS-INDUCED NEUROLOGICAL DISORDER IN MICE - INFECTIONOF NEONATES RESULTS IN IMMUNOPATHOLOGY

Borna disease virus (BDV) is a neurotropic nonsegmented negative-stran ded RNA virus that persistently infects warm-blooded animals. In horse s and other natural animal hosts, infections with BDV cause meningoenc ephalitis and behavioral disturbances. Experimental infection of adult mice takes a nonsymptomatic course, an observation previously believe d to indicate that this animal species is not suitable for pathogenesi s studies. We now demonstrate that BDV frequently induces severe neuro logical disease in infected newborn mice. Signs of neurological diseas e were first observed 4 to 6 weeks after intracerebral infection. They included a characteristic nonphysiological position of the hind limbs at an early stage of the disease and paraparesis at a later stage. Hi stological examination revealed large numbers of perivascular and meni ngeal inflammatory cells in brains of diseased mice and, unexpectedly, no increase in immunoreactivity to glial fibrillar acidic protein. Th e incidence and severity of BDV-induced disease varied dramatically am ong mouse strains. While only 13% of the infected C57BL/6 mice showed disease symptoms, which were mostly transient, more than 80% of the in fected MRL mice developed severe neurological disorder. In spite of th ese differences in susceptibility to disease, BDV replicated to compar able levels in the brains of mice of the various strains used. Intrace rebral infections of newborn beta 2-microglobulin-deficient C57BL/6 an d MRL mice, which both lack CD8(+) T cells, did not result in meningoe ncephalitis or neurological disease, indicating that the BDV-induced n eurological disorder in mice is a cytotoxic T-cell-mediated immunopath ological process. With this new animal model it should now be possible to characterize the disease-inducing immune response to BDV in more d etail.