Failure to detect Borna disease virus antigen and RNA in human blood

Background: Borna disease virus (BDV) is the etiological agent of a rare progressive meningoencephalitis that affects mostly horses and sheep. There is an unresolved debate whether also humans are susceptible to infection with BDV and if so, whether this might be associated with neuropsychiatric diseases. One recent key publication employing an ELISA-based sandwich assay reported prevalences of BDV-specific circulating immune complexes in human blood as high as 30% in the normal population and up to 100% in psychiatric patients [Bode L, Reckwald P. Severus WE, Stoyloff R, Ferszt R, Dietrich DE, et al. Borna disease virus-specific circulating immune complexes, antigenemia, and free antibodies-the key marker triplet determining infection and prevailing in severe mood disorders. Mol Psychiatry 2001;6(4):481-91]. However, this report did not examine for the physical presence of BDV antigens in human blood, and therefore, these seemingly high prevalences may not reflect Borna virus-specific signals. Objectives: We attempted to correlate string plasma signals in the particular sandwich ELISA system with the presence of BDV antigens. Study design: Four preselected plasma samples with high reactivity in the described assay were analysed by immunoaffinity purification and highly sensitive real-time RT-PCR. Results: Neither method did provide any evidence for the presence of viral proteins or nucleic acids. Conclusions: Our findings argue against the concept that the described sandwich ELISA reliably detects BDV-specific antigens in human blood, therefore do not support the hypothesis that BDV is a pathogen of humans. (C) 2006 Elsevier B.V. All rights reserved.