High-dose Borna disease virus infection induces a nucleoprotein-specific cytotoxic T-lymphocyte response and prevention of immunopathology

Experimental Borna disease virus (BDV) infection of rats and natural infect ion of horses and sheep leads to severe central nervous system disease base d on immunopathological pathways. The virus replicates slowly, and the cell ular immune response results in immunopathology. CD8(+) T cells exert effec tor cell functions, and their activity results in the destruction of virus- infected cells. Previously, Oldach and colleagues (D. Oldach, M. C. Zink, J . M. Pyper, S. Herzog, R. Rott, O. Narayan, and J. E. Clements, Virology 20 6:426-434,1995) have reported protection against Borna disease after inocul ation of high-dose cell-adapted BDV. Here we show that the outcome of the i nfection, i.e., immunopathology versus protection, is simply dependent on t he amount of virus used for infection. High-dose BDV (10(6) FFU) triggers a n early virus-specific reaction of the Immune system, as demonstrated by st rong cellular and Immoral responses. In particular, the early presence and function of nucleoprotein-specific CD8(+) T cells could be demonstrated in the brain. We present evidence that in a noncytolytic and usually persisten t virus infection, high-dose input virus mediates early control of the path ogen due to an efficient induction of an antiviral immune mechanism. From t hese data, we conclude that immune reactivity, in particular the cytotoxic T-cell response, determines whether the virus is controlled with prevention of the ensuing immunopathological disease or whether a persistent infectio n is established.