| 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. Recent epidemiological studies revealed that BDV can infect humans and that it may be related with certain neuropsychiatric disorders. A line of recent evidences suggests that BDV infection causes direct damages on brain functions in the absence of immunopathology-related brain damage. In order to elucidate BDV neuropathogenesis, we investigated the features of BDV phosphoprotein (P) in the mechanism of transcriptional and translational regulation in infected cells, as well as in the interaction with host cellular factor. BDV P is an abundant protein in infected animal brains and it is assumed that the protein cooperates with the pol protein to play a pivotal role in viral transcription and replication. In this study, we demonstrate following results. 1. BDV P specifically binds to a 30-kDa neurite outgrowth factor, amphoterin/HMGB1, and P interferes with HMGB1 functions * P-expressed and infected neural cells. 2. BDV P is expressed from a 0.8-kb bicistronic mRNA with a leaky scanning mechanism 3. A novel 16-kDa protein (P') is produced from the same open reading frame of P. 4. The induction of acute fatal disorders in infected gerbils is associated with BDV expression in the brainstem region. 5. BDV P efficiently localizes in the cytoplasm only when BDV X is expressed in the cells. From these observations, we indicate that the expression and intracellular localization of BDV P could be critically regulated by the interaction with other viral proteins. Furthermore, we also suggest that the expression of BDV P may play an important role in the pathogenesis of this virus.
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