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.