We have used the reverse transcriptase-polymerase chain reaction technique to 
gain insight into the pathogenesis of encephalitis caused by Borna disease virus 
(BDV). RNA specific for BDV was first detected in the olfactory bulb of 
intranasally infected rats at 6 days postinfection (p.i.). At 14 days p.i., high 
levels of BDV RNA were found in all brain regions, and at 26 days p.i., 
BDV-specific RNA was also present in the eye, nasal mucosa, and facial skin. In 
the chronic phase of the disease, BDV RNA was identified in many peripheral 
organs but not in blood. Analysis of brain tissue for the presence of cytokine 
mRNAs revealed that the mRNA levels of interleukin-6 (IL-6), tumor necrosis 
factor alpha, and IL-1 alpha had increased sharply at 14 and 26 days p.i. These 
cytokine mRNAs reached maximum levels at the peak of inflammatory reactions and 
decreased drastically in the chronic phase of the disease. Although IL-2 mRNA 
was also found in normal brain, it was markedly increased in BDV-infected brain 
at 14 days p.i. Expression of gamma interferon (IFN-gamma) mRNA, which was not 
observed in normal rat brain, was detected at 14 days p.i. and reached a maximum 
level at 38 days p.i. IL-2 and IFN-gamma mRNA expression correlated with 
expression of CD4 and CD8 mRNAs, indicating that both CD4+ and CD8+ T 
lymphocytes are induced in the early stages of BDV infection. Since IFN-gamma 
and CD8 mRNA levels were still highly elevated in the chronic phase of Borna 
disease, it is likely that CD8+ T lymphocytes act to reduce inflammation and to 
ameliorate neurological signs during the chronic phase of infection.