Borna disease virus (BDV) causes central nervous system (CNS) disease in several 
vertebrate species, which is frequently accompanied by behavioral abnormalities. 
In the adult rat, intracerebral (i.c.) BDV infection leads to immunomediated 
meningoencephalitis. In contrast, i.c. infection of neonates causes a persistent 
infection in the absence of overt signs of brain inflammation. These rats 
(designated PTI-NB) display distinct behavioral and neurodevelopmental 
abnormalities. However, the molecular mechanisms for these virally induced CNS 
disturbances are unknown. Cytokines play an important role in CNS function, both 
under normal physiological and pathological conditions. Astrocytes and microglia 
are the primary resident cells of the central nervous system with the capacity 
to produce cytokines. Strong reactive astrocytosis is observed in the PTI-NB rat 
brain. We have used a ribonuclease protection assay to investigate the mRNA 
expression levels of proinflammatory cytokines in different brain regions of 
PTI-NB and control rats. We show here evidence of a chronic upregulation of 
proinflammatory cytokines interleukin-6, tumor necrosis factor alpha, 
interleukins-1alpha, and -1beta in the hippocampus and cerebellum of the PTI-NB 
rat brain. These brain regions exhibited only a very mild and transient immune 
infiltration. In contrast, in addition to reactive astrocytes, a strong and 
sustained microgliosis was observed in the PTI-NB rat brains. Our data suggest 
that CNS resident cells, namely astrocytes and microglia, are the major source 
of cytokine expression in the PTI-NB rat brain. The possible implications of 
these findings are discussed.