Abstract
Borna disease virus (BDV) can induce neurological disease in animals.1,2 Since viral nucleic acid,3–5 infectious particles6–8 and antibodies recognizing BDV antigens9–11 were found at higher frequencies in psychiatric patients than in healthy controls, BDV is suspected to cause psychiatric disorders in humans. However, the human origin of these viruses has recently been questioned.12 To diagnose BDV infections, sera are usually analyzed for antiviral antibodies by indirect immunofluorescence (IFA) on virus-infected cells.9,10,13 This study reveals that the reactive antibodies in human sera mainly recognized the BDV phosphoprotein, whereas animal sera preferentially detected the viral nucleoprotein. Immunoglobulin (Ig) G in sera of experimentally or naturally infected animals bound to the viral antigen with high avidity, ie resisting 3 M urea, whereas reactive IgG in human sera did not. Longitudinal studies showed that reactive human antibodies persisted for many years without gaining high avidity for BDV antigens, indicating that they were probably not induced by BDV but rather by infection with an antigenically related microorganism of unknown identity or by exposure to other related immunogens.
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Acknowledgements
We thank Kazuhiko Ikeda for providing samples of reactive human serum, Thomas Briese for providing serum samples of an experimentally infected monkey, Martin Schwemmle for help with the transfection experiments, and Otto Haller, Dieter Neumann-Haefelin and Georg Bauer for critical comments on the manuscript.
Financial support was provided by grants from the Zentrum für Klinische Forschung I of the Universitätsklinikum Freiburg, and the Bundesministerium für Bildung und Forschung.
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Allmang, U., Hofer, M., Herzog, S. et al. Low avidity of human serum antibodies for Borna disease virus antigens questions their diagnostic value. Mol Psychiatry 6, 329–333 (2001). https://doi.org/10.1038/sj.mp.4000858
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DOI: https://doi.org/10.1038/sj.mp.4000858