Susceptibility of Borna disease virus to the antiviral action of gamma-interferon: Evidence for species-specific differences

Summary.

Borna disease virus (BDV) infection in its predominant natural host – horses and sheep – leads to fatal meningoencephalomyelitis. The immune-mediated disease can also be induced experimentally in rats following intra- cerebral BDV infection. Despite a vigorous immune response, BDV persists in the central nervous system (CNS) in surviving rats. However, immunization of rats with BDV-specific T-cells prior to challenge with BDV prevents neurological disease and results in virus clearance from the CNS. To analyze whether interferon gamma (IFNγ) might contribute to viral clearance in the rat brain, we tested the susceptibility of BDV to the antiviral action of rat IFNγ using different rat cell lines. Even at high concentrations of IFNγ, BDV infection of astrocyte and fibroblast cell lines as well as of rat embryo cells could not be inhibited efficiently. Similarly, infection of cultured rat hippocampal slices with BDV was not inhibited by rat IFNγ. In contrast, de novo BDV infection of monkey kidney cells as well as human oligodendroglial cells was blocked by preincubation with human IFNγ. Furthermore, IFNγ reduced the BDV load in persistently BDV-infected human oligodendroglial cells but not in infected rat astrocytes. These data suggest species-specific differences in the susceptibility of BDV to the antiviral action of IFNγ.