The humoral and cellular immune response of sheep against Borna disease virus in endemic and non-endemic areas.

Borna Disease (BD) is a mostly fatal disease of horses and sheep endemic in central Europe. Antibodies to Borna disease virus (BDV) have been described in sheep and other species living in BD non-endemic areas. Meaningful clinical BDV serology is hampered by difficulties in defining serological cut-offs, which require the investigation of populations from endemic areas. Here we studied BD serology in sheep from endemic and non-endemic areas of similar geography in Switzerland. Antibodies to BDV antigens were detected by ELISA and indirect immunofluorescence analysis (IFA) only in sera from 3 of 6 sheep with autopsy confirmed BD. One serum was positive by IFA but not by ELISA, while 2 sera were negative in both assays, indicating that not all diseased animals develop BDV specific antibodies. Six % of clinically healthy animals (6/106) from an endemic area and 2% from a non-endemic area (4/192) had serum antibody to either BDV p40 or p24 as detected by ELISA. None of the animals showed a cellular immune response to BDV p40. In some healthy sheep from the endemic area, serum antibody titers to BDV p24 antigen remained elevated over several months without onset of disease symptoms. Infections with either BDV or related viruses may thus occur at low frequency in sheep from non-endemic areas leading to the production of antibodies to BDV antigens. We further propose viral strain differences or environmental factor(s) may determine the clinical outcome.