Induction of protection against Borna disease by inoculation with high-dose-attenuated Borna disease virus

Borna disease is a chronic neurological disease caused by an enveloped negative-strand RNA virus (BDV). Experimentaldisease can be reproduced in rats with brain homogenates derived from infected animals or with virus derived from infected cells in culture. The virus replicates in cultured cells without evidence of cytopathic effect or production of significant levels of cell-free virus. Borna disease is caused by an immunopathological response to viral infection of neural cells. To further investigate the pathogenesis of Borna disease, rats were inoculated with different doses of BDV attenuated by culture in MDCK cells. Low doses of attenuated BDV (10²-10⁴ TCID₅₀) resulted in typical clinical disease and severe encephalitis; however, the lag period between inoculation and disease was considerably longer than that with virulent BDV. In contrast, animals inoculated with a high dose of attenuated BDV (10⁵-10⁶ TCID₅₀) did not develop clinical disease, although a mild encephalitic response was present that did not progress beyond the mild encephalitis. Animals inoculated with a high dose of BDV developed high titers of anti-BDV antibody and were protected against virulent challenge. Protection was correlated with the rapid induction of an immune response in the animals and the lack of any biologically detectable virus in the CNS.