Borna disease virus phosphoprotein expression affects glial functions in the C6 glioma cells

Borna disease virus (BDV) is a highly neurotropic negative-strand RNA virus that belongs to the Mononegavirales. Many reports demonstrated that natural infection of BDV occurs worldwide in a variety of vertebrate species, suggesting that host range of this virus includes all warm-blooded animals. BDV persistently infects the central nervous system (CNS) of many animal species and causes neurobehavioral disorders resembling autism, such as anxiety, aggression, hyperactivity, abnormal play behavior, and cognitive deficits. We previously reported the generation of transgenic mice expressing BDV phosphoprotein (P) selectively in astrocytes. This transgenic mouse, P-Tg, showed striking neurobehavioral abnormalities resembling those in BDV-infected animals, such as enhanced intermale aggressiveness, hyperactivity and spatial reference memory deficit. To reveal the molecular mechanisms how glial cells induce these abnormalities, we performed microarray analysis using C6 rat glioma cells expressing either GFP (C6-GFP) or BDV P (C6-P). Sixty-eight genes are significantly affected in C6-P cells. The genes, whose products are localized at the extracellular region, were enriched in the differentially expressed genes in C6-P cells. Furthermore, gene ontology analysis revealed an emphasis on genes involved in morphogenesis. It is highly likely that the secretion of astrocyte factors may be widely dysregulated in the P-Tg, leading to the astrocyte hypofunction in the brain. The labeled cRNAs were hybridized on 4X44K Agilent Whole Rat Genome dual colour Microarrays (G4130F) in two dye swap experiments, resulting in four individual microarrays.