Gene expression of the TGF-β family in rat brain infected with Borna disease virus

CRNP5, a variant of Borna disease virus (BDV), has stronger pathogenesis in rats than the related variant CRP3, although only 4 amino acids in the whole genome are different. As a first step to clarify the differential pathogenesis between the variants, the present study focused on examining the expression of the transforming growth factor (TGF)-β family in the brain of rats infected with BDV. The main results were as follows. (1) BDV infection, irrespective of the variant, up-regulates TGF-β1 expression in the brain, (2) the expressions of signal receptors for TGF-β1 are also increased, (3) the expression of brain inhibin/activin βE is up-regulated by BDV infection, and (4) the expression of brain inhibin/activin βC tends to be higher in rats exhibiting severe Borna disease. These results indicate that members of the TGF-β family are involved in neuronal disorders induced by BDV infection in a ligand-dependent manner. In particular, up-regulation of inhibin/activin βC may be a key event responsible for induction of the stronger pathogenesis of the CRNP5 variant of BDV.