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Borna disease virus-specific circulating immune complexes, antigenemia, and free antibodies—the key marker triplet determining infection and prevailing in severe mood disorders

Molecular Psychiatry volume 6, pages 481–491 (2001)Cite this article

Abstract

Borna disease virus (BDV), a unique genetically highly conserved RNA virus (Bornaviridae; Mononegavirales),1 preferentially targets neurons of limbic structures2 causing behavioral abnormalities in animals.3,4 Markers5–10 and virus11–13 in patients with affective disorders and schizophrenia have raised worldwide interest.3 A persistent infection was suggestive from follow-up studies,5,14 but inconstant detectability weakened a possible linkage.15This study for the first time discloses that detection gaps are caused by BDV-specific circulating immune complexes (CIC), and their interplay with free antibodies and plasma antigens (p40/p24). Screening 3000 sera each from human and equine patients over the past 4 years by new enzyme immunoassays (EIAs) revealed that BDV-CICs indicate 10 times higher infection rates (up to 30% in controls, up to 100% in patients) than did previous serology.16,17 Persistence of high amounts of CICs and plasma antigens correlates with severity of depression. Even BDV RNA could be detected in plasma samples with strong antigenemia. Our discovery not only explains the course of persistent infection, but offers novel easy-to-use diagnostic tools by which new insights into BDV-related etiopathogenesis of disease and epidemiology are possible.

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Acknowledgements

We are grateful to coworkers at the Crisis Intervention Center (especially Dr H Berzewski) and the Psychiatric Clinic (UKBF) of the Free University of Berlin, and the Department of Psychiatry of the Medical School Hanover (MHH), for data on and care of the patients. We thank A Büchel, T Leiskau, and C Berndt for technical assistance and C Dölle for help with antigen purification and protein measurement. This work was partially supported by previous grants of the Deutsche Forschungsgemeinschaft (Lu 142/5, 1–3) and the European Community (BMH1–CT94–1791) to HL.

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Author notes

  1. L Bode & P Reckwald

    Present address: McLean Hospital, Psychopharmacology Research Laboratory, Harvard Medical School, 115 Mill St, Belmont, 02478, MA, USA

  2. L Bode and H Ludwig: L Bode and H Ludwig have contributed equally to this work

Authors and Affiliations

  1. Project Bornavirus Infections, Robert Koch-Institut, Nordufer 20, Berlin, 13353, Germany

    L Bode & P Reckwald

  2. Crisis Intervention Center, Benjamin Franklin Hospital, Free University of Berlin, Hindenburgdamm 30, Berlin, 12200, Germany

    W E Severus

  3. Institute of Virology, Free University of Berlin, Königin-Luise-Strae 49, Berlin, 14195, Germany

    R Stoyloff & H Ludwig

  4. Department of Gerontopsychiatry, Psychiatric Clinic, Benjamin Franklin Hospital, Free University of Berlin, Eschenallee 3, Berlin, 14050, Germany

    R Ferszt

  5. Department of Psychiatry and Psychotherapy, Medical School of Hanover, Carl-Neuberg Strae 1, Hannover, 30625, Germany

    D E Dietrich

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Correspondence to L Bode.

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Bode, L., Reckwald, P., Severus, W. 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 6, 481–491 (2001). https://doi.org/10.1038/sj.mp.4000909

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