Identification of differentially expressed genes in brains of newborn Borna disease virus-infected rats in the absence of inflammation.

Infection of newborn rats with Borna disease virus (BDV) leads to viral persistence in the central nervous system without overt signs of inflammation. Nevertheless, these rats display distinct behavioral and neurodevelopmental abnormalities. The molecular basis of the latter is still unknown. Using a cDNA array representing 1200 genes, we sought to identify cellular genes which are differentially expressed following perinatal BDV-infection. RNA samples prepared from different brain regions were analysed at various time points before or after BDV-induced defects become evident. In infected brains, we found upregulated expression of genes encoding brain fatty acid binding protein (B-FABP), beta2-microglobulin (beta2m) and, as described previously, the chemokine IP-10. Kinetic studies revealed sustained increased expression of B-FABP in infected frontal cortices beginning about three weeks p.i. Moreover, a slight transient increase of B-FABP expression in infected hippocampi was observed 3-5 weeks p.i. In situ hybridization studies combined with immunohistochemistry suggested that expression of beta2m was predominantly upregulated in glial cells and possibly also in some neurons. Employing cultured infected hippocampus slices and infected genetically modified mice, we provide evidence, that the observed upregulation of beta2m expression is not triggered by IFN-gamma, but rather by IFN-alpha/beta.