Clinical similarities and close genetic relationship of human and animal Borna disease virus

  • L. Bode
  • H. Ludwig
Conference paper


Borna disease virus (BDV) is the prototype genus of a new family, Bornaviridae, within the order Mononegavirales. BDV naturally infects animals and man. The symptomatology in animals ranges from subclinical infection to rare cases of encephalitis. Asymptomatic infection seemed more frequent than expected, based on antibody data from 100 healthy horses derived from different stables with a history of diseased cases (30–40% carriers). Likewise, phasic episodes of a neurobehavioral syndrome followed by recovery were much more common than fatal neurologic disease. They were paralleled by expression of BDV antigens (N-protein p40, P-protein p24) and RNA transcripts in peripheral blood mononuclear cells, indicating viral activation. Representative longitudinal studies showed that episodes of depressive illness in humans as well as apathetic phases in infected horses were accompanied by antigen expression and followed a similar clinical course. After recovery, BDV antigen disappeared. This temporal congruence, together with the recent isolation of infectious BDV from such patients, points to a contributory role of this virus in human affective disorders. Successful amelioration of BDV-induced neurobehavioral disease in horses with antidepressants applied in psychiatry, supported a common viral pathomechanism, involving reversible disturbances of the neurotransmitter network in the limbic system. Sequences of genetic material amplified from infected animal tissue and human PBMCs revealed a close interspecies relationship and high sequence conservation of the BDV genome. In human BDV isolates, however, single unique mutations were prominent in four genes. This finding supports the hypothesis that despite of high genomic conservation, species-specific genotypes may be definable, provided the sequences are derived from RNA of infectious virus.


Healthy Horse Strain Versus Abnormal Eating Behavior Infected Horse Temporal Congruence 
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  1. 1.
    Bode L, Riegel S, Lange W, Ludwig H (1992) Human infections with Borna disease virus: seroprevalence in patients with chronic diseases and healthy individuals. J Med Virol 36: 309–315PubMedCrossRefGoogle Scholar
  2. 2.
    Bode L, Ferszt R, Czech G (1993) Borna disease virus infection and affective disorders in man. Arch Virol [Suppl] 7: 159–167CrossRefGoogle Scholar
  3. 3.
    Bode L, Dürrwald R, Koeppel P, Ludwig H (1994) Neue Aspekte der equinen Borna-Virus-Infektion mit und ohne Krankheit. Diagnoseschema und Einsendeprotokoll. Prakt Tierarzt 75: 1065–1068Google Scholar
  4. 4.
    Bode L, Dürrwald R, Ludwig H (1994) Borna virus infections in cattle associated with fatal neurologic disease. Vet Rec 135: 283–284PubMedCrossRefGoogle Scholar
  5. 5.
    Bode L, Steinbach F, Ludwig H (1994) A novel marker for Borna disease virus infection. Lancet 343: 297–298PubMedCrossRefGoogle Scholar
  6. 6.
    Bode L (1995) Human infections with Borna disease virus and potential pathogenic implications. In: Koprowski H, Lipkin WI (eds) Borna disease. Curr Top Microbiol Immunol 190: 103–130Google Scholar
  7. 7.
    Bode L, Zimmermann W, Ferszt R, Steinbach F, Ludwig H (1995) Borna disease virus genome transcribed and expressed in psychiatric patients. Nature Med 1: 232–236PubMedCrossRefGoogle Scholar
  8. 8.
    Bode L, Dürrwald R, Rantam FA, Ferszt R, Ludwig H (1996) First isolates of infectious human Borna disease virus from patients with mood disorders. Mol Psych 1: 200–212Google Scholar
  9. 9.
    Briese T, De la Torre JC, Lewis A, Ludwig H, Lipkin WI (1992) Borna disease virus, a negative-strand RNA virus, transcribes in the nucleus of infected cells. Proc Natl Acad Sci USA 89: 11486–11489PubMedCrossRefGoogle Scholar
  10. 10.
    Briese T, Schneemann A, Lewis AJ, Park Y-S, Kim S, Ludwig H, Lipkin WI (1994) Genomic organization of Borna disease virus. Proc Natl Acad Sci USA 91: 4362–4366PubMedCrossRefGoogle Scholar
  11. 11.
    Cubitt B, De la Torre JC (1994) Borna disease virus (BDV), a nonsegmented RNA virus, replicates in the nuclei of infected cells where infectious BDV ribonucleo-proteins are present. J Virol 68: 1371–1381PubMedGoogle Scholar
  12. 12.
    Cubitt B, Oldstone C, De la Torre JC (1994) Sequence and genome organization of Borna disease virus. J Virol 68: 1382–1396PubMedGoogle Scholar
  13. 13.
    De la Torre JC (1994) Molecular biology of Borna disease virus: prototype of a new group of animal viruses. J Virol 68: 7669–7675PubMedGoogle Scholar
  14. 14.
    De la Torre JC, Bode L, Dürrwald R, Cubitt B, Ludwig H (1996) Sequence characterization of human Borna disease virus. Virus Res 44: 33–44PubMedCrossRefGoogle Scholar
  15. 15.
    Dittrich W, Bode L, Ludwig H, Kao M, Schneider K (1989) Learning deficiencies in Borna disease virus-infected but clinically healthy rats: Biol Psych 26: 818–828CrossRefGoogle Scholar
  16. 16.
    Gosztonyi G, Ludwig H (1995) Borna disease — neuropathology and pathogenesis. In: Koprowski H, Lipkin WI (eds) Borna disease. Curr Top Microbiol Immunol 190: 39–73Google Scholar
  17. 17.
    Joest E, Degen K (1909) Über eigentümliche Kerneinschlüsse der Ganglienzellen bei der enzootischen Gehirn-Rückenmarksentzündung der Pferde. Z Infkrankh Haustiere 9: 1–98Google Scholar
  18. 18.
    Kishi M, Arimura Y, Ikuta K, Shoya Y, Lai PK, Kakinuma M (1996) Sequence variability of Borna disease virus open reading frame II found in human peripheral blood mononuclear cells. J Virol 70: 635–640PubMedGoogle Scholar
  19. 19.
    Lange H, Herzog S, Herbst W, Schliesser T (1987) Seroepidemiologische Untersuchungen zur Bornaschen Krankheit (ansteckende Gehirn-Rückenmarkentzündung) der Pferde. Tierärztl Umschau 42: 938–946Google Scholar
  20. 20.
    Ludwig H, Bode L, Gosztonyi G (1988) Borna disease: a persistent virus infection of the central nervous system. Prog Med Virol 35: 107–151PubMedGoogle Scholar
  21. 21.
    Ludwig H, Furuya K, Bode L, Klein N, Dürrwald R, Lee DS (1993) Biology and neurobiology of Borna disease viruses (BDV), defined by antibodes, neutralizability and their pathogenic potential. Arch Virol [Suppl] 7: 111–133CrossRefGoogle Scholar
  22. 22.
    Lundgren A-L, Czech G, Bode L, Ludwig H (1993) Natural Borna disease in domestic animals other than horses and sheep. J Vet Med B 40: 298–303CrossRefGoogle Scholar
  23. 23.
    Lundgren A-L, Zimmermann W, Bode L, Czech G, Gosztonyi G, Lindberg R, Ludwig H (1995) Staggering disease in cats: isolation and characterization of the feline Borna disease virus. J Gen Virol 76: 2215–2222PubMedCrossRefGoogle Scholar
  24. 24.
    Narayan O, Herzog S, Frese K, Scheefers H, Rott R (1983) Behavioral disease in rats caused by immunpathological responses to persistent Borna virus in the brain. Science 220: 1401–1403PubMedCrossRefGoogle Scholar
  25. 25.
    Nicolau S, Galloway IA (1928) Borna disease and enzootic encephalomyelitis of sheep and cattle. MRC Spec Rep Series 121: 7–90Google Scholar
  26. 26.
    Rott R, Herzog S, Fleischer B, Winokur A, Amsterdam JD, Dyson W, Koprowski H (1985) Detection of serum antibodies to Borna disease virus in patients with psychiatric disorders. Science 228: 755–756PubMedCrossRefGoogle Scholar
  27. 27.
    Rott R, Herzog S, Bechter K, Frese K (1991) Borna disease, a possible hazard for man? Arch Virol 118: 143–149PubMedCrossRefGoogle Scholar
  28. 28.
    Sauder C, Müller A, Cubitt B, Mayer J, Steinmetz J, Trabert W, Ziegler B, Wanke K, Mueller-Lantzsch N, De la Torre JC, Grösser FA (1996) Detection of Borna disease virus (BDV) antibodies and BDV RNA in psychiatric patients: evidence for high sequence conservation of human blood-derived BDV RNA. J Virol 70: 7713–7724PubMedGoogle Scholar
  29. 29.
    Schneemann A, Schneider PA, Lamb RA, Lipkin WI (1995) The remarkable coding strategy of Borna disease virus: a member of the nonsegmented negative strand RNA viruses. Virology 210: 1–8PubMedCrossRefGoogle Scholar
  30. 30.
    Schneider PA, Briese T, Zimmermann W, Ludwig H, Lipkin WI (1994) Sequence conservation in field and experimental isolates of Borna disease virus. J Virol 68: 63–68PubMedGoogle Scholar
  31. 31.
    Zimmermann W, Breter H, Rudolph M, Ludwig H (1994) Borna disease virus: immunoelectron microscopic characterization of cell-free virus and further information about the genome. J Virol 68: 6755–6758PubMedGoogle Scholar
  32. 32.
    Zimmermann W, Dürrwald R, Ludwig H (1994) Detection of Borna disease virus RNA in naturally infected animals by a nested polymerase chain reaction. J Virol Methods 46: 133–143PubMedCrossRefGoogle Scholar
  33. 33.
    Zwick W (1939) Bornasche Krankheit und Enzephalomyelitis der Tiere. In: Gildenmeister E, Haagen E, Waldmann O (eds) Handbuch der Viruskrankheiten, vol 2. Fischer, Jena, pp 254–354Google Scholar

Copyright information

© Springer-Verlag Wien 1997

Authors and Affiliations

  • L. Bode
    • 1
  • H. Ludwig
    • 2
  1. 1.Department of VirologyRobert Koch-InstitutBerlinFederal Republic of Germany
  2. 2.Institute of VirologyFree University of BerlinBerlinFederal Republic of Germany

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