Characterization of the acute immune response in the retina of Borna disease virus infected Lewis rats.

In Lewis rats infected intracerebrally with the highly neurotropic Borna disease virus (BDV), the retina is one of the most severely affected central nervous system (CNS) structures. While BDV-induced damage in the brain has been previously shown to be caused by a T-cell-dependent process, the immunopathological mechanisms leading to BDV-induced retinitis remain to be elucidated. RNA samples from retinae were subjected to RNase protection assays to detect transcripts of proinflammatory cytokines and chemokines known to be involved in the recruitment of T-cells and macrophages in the CNS. The observed expression profile of proinflammatory cytokines and chemokines, as well as the immunohistochemical detection of alpha beta TCR-positive, CD4- and CD8-positive T-cells in the BDV-infected retinae, is reminiscent of the situation observed in the brains of Lewis rats during the acute phase of Borna disease (BD). This suggests that similar immunopathological mechanisms are operating in retinae and brains of infected rats.

Viral-induced inflammation is accompanied by beta-amyloid plaque reduction in brains of amyloid precursor protein transgenic Tg2576 mice.

Amyloid plaques, one of the neuropathological hallmarks of Alzheimer's disease, and their main constituent, the amyloid beta-peptide (Abeta), are triggers of the activation of innate inflammatory mechanisms involving the activation of microglia. To dissect the effects of a non-Abeta-specific microglial activation on the Abeta metabolism, we employed a viral infection-based model. Transgenic mice expressing a mutated form of the human amyloid precursor protein (Tg2576) were used. In preceding experiments, 2-week-old transgenic mice and non-transgenic littermates were infected intracerebrally with the neurotropic Borna disease virus and investigated at 2, 4 and 14 weeks post-infection. The Borna disease virus-inoculated mice showed a persisting, subclinical infection of cortical and limbic brain areas characterized by slight T-cell infiltrates, expression of cytokines and a massive microglial activation in the hippocampus and neocortex. Viral-induced effects reached their peak at 4 weeks post-infection. In 14-month-old Tg2576 mice, characterized by the deposition of diffuse and dense-core amyloid plaques in cortical brain regions, Borna disease virus-induced microglial activation in the vicinity of Abeta deposits was used to investigate the influence of a local inflammatory response on these deposits. At 4 weeks post-infection, histometric analyses employing Abeta immunohistochemistry revealed a decrease of the cortical and hippocampal Abeta-immunopositive area. This overall decrease was accompanied by a decrease of parenchymal thioflavin-S-positive amyloid deposits and an increase of such deposits in the walls of cerebral vessels, which indicates that the elicitation of a non-Abeta-specific microglial activation may contribute to a reduction of Abeta in the brain parenchyma.