Chemokine gene expression in astrocytes of Borna disease virus-infected rats and mice in the absence of inflammation

Borna disease virus (BDV) causes CD8(+) T-cell-mediated meningoencephalitis in immunocompetent mice and rats, thus providing a valuable animal model f or studying the mechanisms of virus-induced central nervous system (CNS) im munopathology. Chemokine-mediated leukocyte recruitment to the CNS is a cru cial step in the development of neurological disease. We found increased mR NA levels of IP-10 and other chemokines in brains of adult rats following i nfection with BDV. The marked increase in chemokine gene expression at abou t day 8 postinfection seemed to immediately precede the inflammatory proces s. In brains of rats infected as newborns, in which inflammation was only m ild and transient, sustained expression of IP-10 and RANTES genes was obser ved. In situ hybridization studies revealed that astrocytes were the major source of IP-10 mRNAs in brains of rats infected as newborns and as adults. In brains of infected mice lacking CD8(+) cells (beta 2m(0/0)), transcript s encoding IP-10 and RANTES were also observed. IP-10 transcripts were also present in a small number of scattered astrocytes of infected knockout mic e lacking mature B and T cells as well as functional alpha/beta and gamma i nterferon receptors, indicating that BDV can induce chemokine synthesis in the absence of interferons and other B- or T-cell-derived cytokines. These data provide strong evidence that CNS-resident cells are involved in the ea rly localized host immune response to infection with BDV and support the co ncept that chemokines are pivotal for the initiation of virus-induced CNS i nflammation.