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Biology and neurobiology of Borna disease viruses (BDV), defined by antibodies, neutralizability and their pathogenic potential

  • H. Ludwig
  • K. Furuya
  • L. Bode
  • N. Klein
  • R. Dürrwald
  • D. S. Lee
Part of the Archives of Virology book series (ARCHIVES SUPPL, volume 7)

Summary

Borna disease viruses (BDV) isolated from more than 20 naturally infected horses, 2 sheep and a possible feline isolate were included in these studies. Most of these wild-type viruses were grown in rabbit cells. Specifically rabbit-adapted viruses establish persistent infection in immortalized cell lines of various animal species. Brain-, tissue culture-, and cell-free released viruses could all be neutralized with antibodies from naturally and experimentally infected animals (horse; hamster, rat, rabbit, mouse, and chicken), with highest titres in birds. Splenectomized rabbits, which were subsequently infected with BDV, efficiently produced high titres of neutralizing antibodies. All of the neutralizing sera and cerebrospinal fluids from infected animals inhibited tissue culture spread of BDV. Experimental infection and hyperimmunization induced antibodies directed against the major components of the soluble antigen (60, 40/38, 25 and 14.5 kD proteins). Analysis of the s-antigen complex with these sera and 6 stable monoclonal antibodies revealed that it consists of 40/38 and 25 kD proteins. Although each of these antibodies detected intracellular virus-specific structures they did not recognize outer plasmamembrane antigens, showed no cross-reactivity, and had no neutralizing capacity. Unifying pathogenetic concepts of this neurotropic virus and its structural elements are discussed.

Keywords

Tree Shrew Infected Rabbit Infected Horse Hyperimmune Seron Equine Dermal 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. 1.
    Bause-Niedrig I, Pauli G, Ludwig H (1991) Borna disease virus-specific antigens: two different proteins identified by monoclonal antibodies. Vet Immunol Immunopathol 27: 293–301PubMedCrossRefGoogle Scholar
  2. 2.
    Beutin L, Bode L, Ozel M, Stephan R (1990) Enterohemolysin production is associated with a temperate bacteriophage in E. cou serogroup 026 strains. J Bacteriol 172: 6469–6475Google Scholar
  3. 3.
    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
  4. 4.
    Bode L, Ferszt R, Czech G (1993) Borna disease virus infection and affective disorders in man. In: Kaaden OR, Eichhorn W, Czerny CP (eds) Unconventional agents and unclassified viruses. Springer, Wien New York, pp 159–167 (Arch Virol [Suppl] 7 )Google Scholar
  5. 5.
    Bode L, Riegel S, Lange W, Ludwig H (1992) Human infections with Borna disease virus: seroprevalence in patients with chronic disease and healthy individuals. J Med Virol 36: 309–315PubMedCrossRefGoogle Scholar
  6. 6.
    Carbone K, Moench T, Lipkin WI (1991) Borna disease virus replicates in astrocytes, Schwann cells and ependymal cells in persistently infected rats; location of viral genomic and messenger RNAs by in situ hybridization. J Neuropathol Exp Neurol 50: 204–214CrossRefGoogle Scholar
  7. 7.
    Carbone KM, Duchala CS, Griffin JW, Kincaid AL, Narayan O (1987) Pathogenesis of Borna disease in rats: Evidence that intra-axonal spread is the major route for virus dissemination and the determinant for disease incubation. J Virol 61: 3431–3440PubMedGoogle Scholar
  8. 8.
    Danner K, Lüthgen K, Herlyn M, Mayr A (1978) Vergleichende Untersuchungen über Nachweis und Bildung von Serumantikörpern gegen das Borna-Virus. Zbl Vet Med B 25: 345–355Google Scholar
  9. 9.
    Dietzschold B, Kao M, Zheng Y, Chen Z, Maul G, Fu Z, Rupprecht CE, Koprowski H (1992) Delineation of putative mechanisms involved in antibody-mediated clearance of rabies virus from the central nervous system. Proc Natl Acad Sci USA 89: 7252–7256PubMedCrossRefGoogle Scholar
  10. 10.
    Dimmock N (1984) Mechanisms of neutralzation of animal viruses. J Gen Virol 65: 1015–1022PubMedCrossRefGoogle Scholar
  11. 11.
    Dittrich W, Bode L, Kao M, Schneider K (1989) Learning deficiencies in Borna disease virus-infected but clinically healthy rats. Biol Psychiatry 26: 818–828PubMedCrossRefGoogle Scholar
  12. 12.
    Furuya K, Noro S, Sakurada N (1984) Production of monoclonal antibodies to influenza virus A/USSR/92/77 (H1N1) and their application to epidemiological study. Rep Hokkaido Inst Publ Health 34: 1–10Google Scholar
  13. 13.
    Gosztonyi G, Ludwig H (1984) Neurotransmitter receptors and viral neurotropism. Neuropsychiatr Clinica 3: 107–114Google Scholar
  14. 14.
    Gosztonyi G, Ludwig H (1984) Borna disease of horses: An immunohistological and virological study of naturally infected animals. Acta Neuropathol 64: 213–221PubMedCrossRefGoogle Scholar
  15. 15.
    Gosztonyi G, Dietzschold B, Kao M, Rupprecht CE, Ludwig H, Koprowski H (1993) Rabies and Borna disease: A comparative pathogenetic study of two neurovirulent agents. Lab Invest 68: 285–295PubMedGoogle Scholar
  16. 16.
    Haas B, Becht H, Rott R (1986) Purification and properties of an intra-nuclear virus-specific antigen from tissue infected with Borna disease virus. J Gen Virol 67: 235–241PubMedCrossRefGoogle Scholar
  17. 17.
    Herzog S, Kompter C, Frese K, Rott R (1984) Replication of Borna disease virus in rats: age-dependent differences in tissue distribution. Med Microbiol Immunol 173: 171–177PubMedCrossRefGoogle Scholar
  18. 18.
    Heinig A (1969) Die Bornasche Krankheit der Pferde und Schafe. In: Röhrer (ed) Handbuch der Virusinfektionen bei Tieren, Vol 4. Gustav-Fischer, Jena, pp 83–148Google Scholar
  19. 19.
    Hiepe T (1958) Die Bornasche Krankheit. Habilitationsschrift, University of LeipzigGoogle Scholar
  20. 20.
    Hirano N, Kao M, Ludwig H (1983) Persistent, tolerant or subacute infection in Borna disease virus-infected rats. J Gen Virol 64: 1521–1530PubMedCrossRefGoogle Scholar
  21. 21.
    Kao M, Ludwig H, Gosztonyi G (1984) Adaptation of Borna disease virus to the mouse. J Gen Virol 65: 1845–1849PubMedCrossRefGoogle Scholar
  22. 22.
    Kennedy-Stoskopf S, Narayan O (1986) Neutralizing antibodies to Visna lentivirus: Mechanism of action and possible role in virus persistence. J Virol 59: 37–44PubMedGoogle Scholar
  23. 23.
    Klein N (1990) Reinigung und Charakterisierung Bornavirus-spezifischer s-Antigenkomponenten. Vet Med Diss, FU BerlinGoogle Scholar
  24. 24.
    Köhler G, Milstein C (1975) Continuous cultures of fused cells secreting antibody of predefined specificity. Nature 256: 495–497PubMedCrossRefGoogle Scholar
  25. 25.
    Krey HF, Ludwig H, Boschek CB (1979a) Multifocal retinopathy in Borna disease virus infected rabbits. Am J Ophthalmol 87: 157–164PubMedGoogle Scholar
  26. 26.
    Krey HF, Ludwig H, Gierend M (1981) Borna disease virus-induced retino-uveitis treated with immunosuppressive drugs. Graefes Arch Clin Exp Ophthalmol 216: 111–119CrossRefGoogle Scholar
  27. 27.
    Lipkin WI, Travin GH, Carbone KM, Wilson MC (1990) Isolation and characterization of Borna disease agent cDNA clones. Proc Natl Acad Sci USA 87: 4184–4188PubMedCrossRefGoogle Scholar
  28. 28.
    Ludwig H, Becht H (1977) Borna disease-a summary of our present knowledge. In: ter Meulen, Katz (eds) Slow virus infections of the central nervous system. Springer, Berlin Heidelberg New York, pp 75–83Google Scholar
  29. 29.
    Ludwig H, Becht H, Groh L (1973) Borna disease (BD), a slow virus infection. Biological properties of the virus. Med Microbiol Immunol 158: 275–289PubMedCrossRefGoogle Scholar
  30. 30.
    Ludwig H, Koester V, Pauli G, Rott R (1977) The cerebrospinal fluid of rabbits infected with Borna disease virus. Arch Virol 55: 209–223PubMedCrossRefGoogle Scholar
  31. 31.
    Ludwig H, Pauli G, Gierend M (1984) Nachweis von Oberflächen Antigenen auf Borna Virus infizierten Zellen. Berl Witch Tierärztl Wochenschr 97: 47–51Google Scholar
  32. 32.
    Ludwig H, Thein P (1977) Demonstration of specific antibodies in the central nervous system of horses naturally infected with Borna disease virus. Med Microbiol Immunol 163: 215–226PubMedCrossRefGoogle Scholar
  33. 33.
    Ludwig H, Kraft W, Kao M, Gosztonyi G, Dahme E, Krey HF (1985) Die Borna-Krankheit bei natürlich und experimentell infizierten Tieren: Ihre Bedeutung für Forschung und Praxis. Tierärztl Praxis 13: 421–453Google Scholar
  34. 34.
    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
  35. 35.
    Lundgren A-L, Czech G, Bode L, Ludwig H (1993) Natural Borna disease in domestic animals others than horses and sheep. J Vet Med B 40: 298–303CrossRefGoogle Scholar
  36. 36.
    McClure MA, Thibault KJ, Hatalski CG, Lipkin WI (1992) Sequence similarity between Borna disease virus p40 and a duplicated domain within the Paramyxovirus and Rhabdovirus polymerase proteins. J Virol 66: 6572–6577PubMedGoogle Scholar
  37. 37.
    Morrison DK, Carter JK, Moyer KW (1985) Isolation and characterization of monoclonal antibodies directed against two subunits of rabbit poxvirus-associated, DNA-directed RNA polymerase. J Virol 9: 670–680Google Scholar
  38. 38.
    Narayan O, Herzog S, Frese K, Scheefers H, Rott R (1983) Pathogenesis of Borna disease in rats: Immune-mediated viral ophthalmoencephalopathy causing blindness and behavorial abnormalities. J Infect Dis 148: 305–315PubMedCrossRefGoogle Scholar
  39. 39.
    Nitzschke E (1963) Untersuchungen über die experimentelle Bornavirus-Infektion bei der Ratte. Zentralbl Veterinarmed [B] 10: 470–527CrossRefGoogle Scholar
  40. 40.
    Pauli G, Ludwig H (1985) Increase of virus yields and release of Borna disease virus from persistently infected cells. Virus Res 2: 29–33PubMedCrossRefGoogle Scholar
  41. 40a.
    Pauli G, Grunmach J, Ludwig H (1984) Focus-immunoassay for Borna disease virus-specific antigens. Zentralbl Veterinarmed [B] 31: 552–557CrossRefGoogle Scholar
  42. 41.
    Richt JA, Herzog S, Binz T, Niemann H, Clements JE, Narayan O, Rott R (1993) Borna disease virus: nature of the agent and significance of infection in man. In: Kaaden OR, Eichhorn W, Czerny CP (eds) Unconventional agents and unclassified viruses. Springer, Wien New York, pp 101–109 (Arch Virol [Suppl] 7 )Google Scholar
  43. 42.
    Rott R, Herzog S, Fleischer B, Winokur H, 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
  44. 43.
    Sasaki S, Ludwig H (1993) In Borna disease virus infected rabbit neurons 100 nm particle structures accumulate at areas of Joest-Degen inclusion bodies. J Vet Med B40: 291–297CrossRefGoogle Scholar
  45. 44.
    Skjodt K, Schou C, Koch C (1984) Assay for the specificity of monoclonal antibodies in crossed immunoelectrophoresis. J Immunol Methods 72: 243–249PubMedCrossRefGoogle Scholar
  46. 45.
    Sprankel H, Richarz K, Ludwig H, Rott R (1978) Behavior alterations in tree shrews (Tupaia glis, Diard 1820) induced by Borna disease virus. Med Microbiol Immunol 165: 1–18PubMedCrossRefGoogle Scholar
  47. 46.
    Stitz L, Sobbe M, Bilzer T (1992) Preventive effects of early anti-CD4 or anti-CD8 treatment on Borna disease in rats. J Virol 66: 3316–3323PubMedGoogle Scholar
  48. 47.
    Stitz L, Bilze T, Richt JA, Rott R (1993) Pathogenesis of Borna disease. In: Kaaden OR, Eichhorn W, Czerny CP (eds) Unconventional agents and unclassified viruses. Springer, Wien New York, pp 135–151 (Arch Virol [Suppl] 7 )Google Scholar
  49. 48.
    Thiedemann W, Presek P, Rott R, Stitz L (1992) Antigenic relationship and further characterization of two major Borna disease virus-specific proteins. J Gen Virol 73: 1057–1064PubMedCrossRefGoogle Scholar
  50. 49.
    Van de Woude S, Richt JA, Zink MC, Rott R, Narayan O, Clements JE (1990) A Borna virus cDNA encoding a protein recognized by antibodies in humans with behavorial diseases. Science 250: 1278–1281CrossRefGoogle Scholar
  51. 50.
    Wara DW (1981) Host defense against streptococcus pneumoniae: The role of the spleen. Rev Infect Dis 3: 299–309PubMedCrossRefGoogle Scholar
  52. 51.
    Zwick W (1939) Bornasche Krankheit and Encephalomyelitis der Tiere. In: Gildenmeister, Haagen, Waldmann (eds) Handbuch der Viruskrankheiten II. Fischer, Jena, pp 254–354Google Scholar

Copyright information

© Springer-Verlag 1993

Authors and Affiliations

  • H. Ludwig
    • 1
    • 4
  • K. Furuya
    • 1
  • L. Bode
    • 2
  • N. Klein
    • 1
  • R. Dürrwald
    • 3
  • D. S. Lee
    • 1
  1. 1.Institute of VirologyFree University of BerlinBerlinGermany
  2. 2.Department of VirologyRobert Koch-Institut, BGABerlinGermany
  3. 3.Institute of MicrobiologyUniversity of LeipzigLeipzigFederal Republic of Germany
  4. 4.Institute of VirologyFree University of BerlinBerlinFederal Republic of Germany

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