| Research Abstract |
Borna disease virus (BDV) belongs to the Bornaviridae family, within the nonsegmented negative-strand RNA virus, Mononegavirales, which is characterized by highly neurotropic, noncytopathic replication, and persistent infection. Although previous studies using rodent models indicated that modulation of the immune response could contribute to the induction of persistence in the brain, the mechanisms by which CNS viruses efficiently control immune response have not been yet fully elucidated. Furthermore, little is known about the glial reactions contributing to the viral persistence and immune modulation in the CNS. In this study, we investigated the role of a pattern recognition receptor, RAGE (receptor for advanced glycation end products), which is involved in the immune system's response pathways, as well as an astrocyte-derived factor, S100B, in the brains of Lewis rats persistently infected with BDV. A prominent role of S100B appears to be the promotion of vascular inflammatory resp
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onses through interaction with the RAGE. We demonstrated that the expression of S100B is significantly reduced in BDV-infected brains despite severe astrocytosis with increased glial fibrillary acidic protein immunoreactivity. Interestingly, no upregulation of the expression of S100B, or RAGE, was observed in the persistently infected brains even on incitation with several inflammatory stimuli, including lipopolysaccharide. In addition, the expression of the vascular cell adhesion molecule, VCAM-1, as well as the infiltration of encephalitogenic T-cells, was significantly reduced in persistently infected brains in which an experimental autoimmune encephalomyelitis was induced by immunization with myelin-basic protein. Furthermore, we demonstrated that the continuous activation of S1008 in the brain may be necessary for the progression of vascular immune responses in neonatally infected rat brains. Our results suggested that BDV infection may impair astrocyte functions via a downregulation of S100B expression, leading to the maintenance of a persistent infection. Less
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