Significant Differences in the Borna Virus p24 Region Between Nucleotide Sequences from Humans in Australia and Reference European Strains

Abstract

Aim Borna Virus (BV) is a negative strand RNA virus associated with neurological diseases in animals. An association with human neuro-psychiatric disease has been suggested. The hypothesis investigated was that potentially infectious levels of blood borne BV may be present in humans. Levels of antibody to BV in human and cat sera were studied by ELISA with antigen from infected horse brain, immunofluorescence with infected cells, Western blot and BV epitope peptide-ELISA. Monoclonal antibodies were used in capture ELISAs to measure BV antigen levels (BVAg) in plasma and RT-PCR and sequencing used to investigate relatedness of BV sequences from humans in Australia with European sequences. Result In 1% of blood donors, free BV antigen was detected in plasma and reactions with BV p24 or p40 antigens confirmed by Western Blot. Circulating immune complexes, antibody to brain-derived antigen and reactions with two of the eight peptides tested were also detected. Strong positive reactions in tests for circulating immune complexes, free plasma antigen and free antibody, were observed in a small number of blood donors. Individuals with high levels of plasma antigen were investigated by RT-PCR and sequencing. Sequence from the p24 region of the Australian human BV genome was 5% different from European reference strains. Conclusion These data support the hypothesis that a form of BV is endemic in humans in Australia, including potentially infectious levels in blood donors. The extent of difference, in regions other than p24, between BV in Australia and strains infecting animals overseas remains to be clarified.