Skip to main content
PMC home page
Brain Pathology logoLink to Brain Pathology
. 2006 Apr 5;10(1):39–48. doi: 10.1111/j.1750-3639.2000.tb00241.x

Distribution of Borna Disease Virus in the Brain of Rats Infected with an Obesity‐inducing Virus Strain

C Herden 1,2, S Herzog 1, J A Richt 1, A Nesseler 2, M Christ 1, K Failing 3, K Frese 2,✉
PMCID: PMC8098463  PMID: 10668894

Abstract

Experimental infection of Lewis rats with Borna disease virus (BDV), a nonsegmented, single‐stranded RNA virus, usually causes an immune‐mediated biphasic neurobehavioral disorder. Such animals develop a persistent infection of the CNS with viral antigen expression in all brain regions and a disseminated nonpurulent meningoencephalitis. Interestingly, intracerebral infection of Lewis rats with a BDV‐variant (BDV‐ob) causes a rapid increase of body weight with the development of an obesity syndrome without obvious neurological signs. The obese phenotype is correlated with a characteristic distribution of inflammatory lesions and BDV‐antigen in the rat brain. Infiltration with mononuclear immune cells and viral antigen expression are restricted to the septum, hippocampus, amygdala and ventromedian tuberal hypothalamus. Therefore, infection with the obesity‐inducing BDV‐ob results most likely in neuroendocrine dysregulations leading to the development of an obesity syndrome. This might be due to the restriction of viral antigen expression and inflammatory lesions to brain areas which are involved in the regulation of body weight and food intake. The BDV‐induced obesity syndrome represents a model for the study of immune‐mediated neuroendocrine disorders caused by viral infections of the CNS.

Full Text

The Full Text of this article is available as a PDF (378.5 KB).

References

  • 1. Amsterdam J, Winokur A, Dyson W, Herzog S, Gonzales S, Rott R, Koprowski H (1985) Borna disease virus: a possible etiologic factor in human affective disorders Arch Gen Psychol 42: 1093–1096. [DOI] [PubMed] [Google Scholar]
  • 2. Bechter K, Herzog S, Estler HC, Schüttler R (1998) Increased psychiatric comorbidity in Borna disease virus seropositive psychiatric patients. Acta Psychiatr Belg 98: 190–204. [Google Scholar]
  • 3. Bechter K, Herzog S, Schüttler R (1992) Case of neurological and behavioral abnormalities: due to Borna disease virus encephalitis Psychiatry Res 42:193–196. [DOI] [PubMed] [Google Scholar]
  • 4. Beck B, Burlet A, Bazin R, Nicolas JP, Burlet C (1993) Elevated neuropeptide Y in the arcuate nucleus of young obese Zucker rats may contribute to the development of their overeating. J Nutr 123: 1168–1172. [DOI] [PubMed] [Google Scholar]
  • 5. Bernard A, Fevre‐Montagne M, Bencsik A, Giraudon P, Wild TF, Confaveux C, Belin MF (1993) Brain structures selectively targeted by canine distemper virus in a mouse model infection. J Neuropathol Exp Neurol 52: 471–480. [DOI] [PubMed] [Google Scholar]
  • 6. Biesenbach W, Herzog S, Frese K (1990) Peripheral neuropathy in experimental Borna disease virus infection in Lewis rats. Schweiz Arch Tierheilk 132:145. [Google Scholar]
  • 7. Binz T, Lebelt J, Niemann H, Hagenau K (1995) Sequence analysis of the p24 gene of Borna disease virus in naturally infected horse, donkey and sheep. Virus Res 34: 281–289. [DOI] [PubMed] [Google Scholar]
  • 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: 200–212. [PubMed] [Google Scholar]
  • 9. Bode L, Zimmermann W, Ferszt R, Steinbach F, Ludwig H (1995) Borna disease virus genome transcribed and expressed in psychiatric patients. Nature Med 1: 232–236. [DOI] [PubMed] [Google Scholar]
  • 10. Bray GA, York DA (1979) Hypothalamic and genetic obesity in experimental animals. Physiol Rev 59: 719–803. [DOI] [PubMed] [Google Scholar]
  • 11. Bray GA, York DA (1998) The MONA LISA hypothesis in the time of leptin. Recent Prog Horm Res 53: 95–118. [PubMed] [Google Scholar]
  • 12. Bredthauer D, Blähser S, Frese K, Herzog S, Rott R (1990) Neuropeptides and obesity: distribution throughout the brain of rats experimentally infected with Borna disease virus In: Brain‐Perception‐Cognition, Proceedings of the 18th Göttingen Neurobiology Conference, Elsner N, Roth G (eds), p. 330, Thieme, Stuttgart , New York . [Google Scholar]
  • 13. Caplazi P, Waldvogel A, Stitz L, Braun U, Ehrensperger F (1994) Borna disease in naturally infected cattle. J Comp Pathol 111: 65–72. [DOI] [PubMed] [Google Scholar]
  • 14. Carp RI, Callahan SM, Sersen EA, Moretz RC (1984) Preclinical changes in weight of scrapie‐infected mice as a function of scrapie agent‐mouse strain combination. Intervirology 21: 61–69. [DOI] [PubMed] [Google Scholar]
  • 15. Carp RI, Kim YS, Callahan SM (1989) Scrapie‐induced alterations in glucose tolerance in mice. J Gen Virol 70: 827–835. [DOI] [PubMed] [Google Scholar]
  • 16. Cubitt B, Oldstone M, De‐la‐Torre JC (1994) Sequence and genomic organization of Borna disease virus. J Virol 68:1383–1396. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 17. Danner K (1982) Borna‐Virus und Borna‐Infektionen. Vom Miasma zum Modell, Enke: Stuttgart . [Google Scholar]
  • 18. De‐la‐Torre JC (1994) Molecular biology of Borna disease: prototype of a new group of animal viruses. J Virol 68: 7669–7675. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 19. De‐la‐Torre JC, Gonzalez‐Dunia D, Cubitt B, Mallory M, Mueller‐Lantzsch N, Graesser FA, Hansen LA, Masliah E (1996) Detection of Borna disease virus antigen and RNA in human autopsy brain samples from neuropsychiatric patients. Virology 223: 272–282. [DOI] [PubMed] [Google Scholar]
  • 20. Deschl U, Stitz L, Herzog S, Frese K, Rott R (1990) Determination of immune cells and expression of major histocompability complex class II antigen in encephalitic lesions of experimental Borna disease. Acta Neuropathol 81: 41–50. [DOI] [PubMed] [Google Scholar]
  • 21. Dixon WJ (1993) BMDP Statistical Software Manual, Vol 1, 2, University of California Press: Berkeley , Los Angeles , London . [Google Scholar]
  • 22. Gies U, Bilzer T, Stitz L, Staiger JF (1998) Disturbance of the cortical cholinergic innervation in Borna disease prior to encephalitis. Brain Pathol 8: 39–48. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 23. Gosztonyi G, Ludwig H (1995) Borna disease‐neuropathology and pathogenesis. Curr Top Microbiol Immunol 190: 39–74. [PubMed] [Google Scholar]
  • 24. Haas B, Becht H, Rott R (1986) Purification and properties of an intranuclear virus‐specific antigen from tissues infected with Borna disease virus. J Gen Virol 67: 235–241. [DOI] [PubMed] [Google Scholar]
  • 25. Heinig A (1969) Die Bornasche Krankheit der Pferde und Schafe In: Handbuch der Viruskrankheiten der Tiere, Röhrer H (ed), PP. 83–137, Fischer: Jena . [Google Scholar]
  • 26. Herzog S, Pfeuffer I, Haberzettl K, Feldmann H, Frese K, Bechter K, Richt JA (1997) Molecular characterization of Borna disease virus from naturally infected animals and possible links to human disorders. Arch Virol (Suppl) 13: 183–190. [DOI] [PubMed] [Google Scholar]
  • 27. Herzog S, Rott R (1980) Replication of Borna disease virus in cell cultures. Med Microbiol Immunol 168:153–158. [DOI] [PubMed] [Google Scholar]
  • 28. Kim YS, Carp RI, Callahan SM, Wisniewski HM (1987) Scrapie‐induced obesity in mice. J Infect Dis 156: 402–405. [DOI] [PubMed] [Google Scholar]
  • 29. Lundgren AL, Czech G, Bode L, Ludwig H (1993) Natural Borna disease in domestic animals other than horses and sheep. Zbl Vet Med 40: 298–303. [DOI] [PubMed] [Google Scholar]
  • 30. Lyons MJ, Faust IM, Hemmes RB, Buskirk DR, Hirsch J, Zabriskie JB (1982) A virally induced obesity syndrome in mice. Science 216: 82–85. [DOI] [PubMed] [Google Scholar]
  • 31. Nagashima K, Zabriskie JB, Lyons MJ (1992) Virus‐induced obesity syndrome: association with a hypothalamic lesion. J Neuropathol Exp Neurol 51: 101–109. [DOI] [PubMed] [Google Scholar]
  • 32. Narayan O, Herzog S, Frese K, Scheefers R, Rott R (1983a) Behavioral disease in rats caused by an immunopathological response to persistent Borna virus in the brain. Science 220: 1401–1403. [DOI] [PubMed] [Google Scholar]
  • 33. Narayan O, Herzog S, Frese K, Scheefers R, Rott R (1983b) Pathogenesis of Borna disease in rats: immunemediated viral opthalmoencephalopathy causing blindness and behavioral abnormalities. J Infect Dis 148: 305–315. [DOI] [PubMed] [Google Scholar]
  • 34. Oldstone MB (1997) How viruses escape from cytotoxic T lymphocytes: molecular parameters and players. Virology 234: 179–185. [DOI] [PubMed] [Google Scholar]
  • 35. Orlich M, Rott R (1994) Thermolysin activation mutants with changes in the fusogenic region of an influenza virus hemagglutinin. J Virol 68: 7537–7539. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 36. Paxinos G, Watson C (1998) The rat brain in stereotaxic coordinates, 4th Edition, Academic Press: San Diego , London . [Google Scholar]
  • 37. Reed L, Münch H (1938) A simple method of estimating fifty percent endpoints. Am J Hyg 27: 493–497. [Google Scholar]
  • 38. Richt JA, Schmeel A, Frese K, Carbone KM, Narayan O, Rott R (1994) Borna disease virus‐specific T‐cells protect against or cause immunopathological Borna disease. J Exp Med 179: 1467–1473. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 39. Richt JA, Stitz L, Wekerle H, Rott R (1989) Borna disease, a progressive meningoencephalitis as a model for CD4+ T‐cell mediated immunopathology in the brain. J Exp Med 170:1045–1050. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 40. Rohner‐Jeanrenaud F, Walker CD, Greco‐Peretto R, Jeanrenaud B (1989) Central corticotropin‐releasing factor administration prevents the excessive body weight gain of genetically obese (fa/fa) rats. Endocrinology 124: 733–739. [DOI] [PubMed] [Google Scholar]
  • 41. Rott R, Becht H (1995) Natural and experimental Borna disease in animals. Curr Top Mircobiol Immunol 190: 17–30. [DOI] [PubMed] [Google Scholar]
  • 42. Rott R, Herzog S, Fleischer B, Winokur A, Amsterdam J, Dyson W, Koprowski H (1985) Detection of serum antibodies to Borna disease virus in patients with psychiatric disorders. Science 228: 1755–1756. [DOI] [PubMed] [Google Scholar]
  • 43. Sanacora G, Kershaw M, Finkelstein JA, White JD (1990) Increased hypothalamic content of preproneuropeptide Y messenger ribonucleic acid in genetically obese Zucker rats and its regulation by food deprivation. Endocrinology 127:730–737. [DOI] [PubMed] [Google Scholar]
  • 44. Schmeel A, Frese K, Richt JA (1995) Immunopathogenesis of Borna disease in rats: role of BDV‐specific TH1‐cells in induction and prevention of Borna disease. In: Immunobiology of viral infections, Schwyzer M, Ackermann M, Bertoni G, Kocherhans R, Mackulough K, Engels M, Wittek R, Zanoni R (eds), pp. 182–187, Foundation Marcel Merieux, Lyon . [Google Scholar]
  • 45. 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: 63–68. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 46. Schüppel KF, Kinne J, Reinacher M (1994) Bornavirus‐Antigennachweis bei Alpakas (Lama pacos) sowie bei einem Faultier (Cholepus didactylus) und einem Zwergflußpferd. Verh ber Erkrg Zootiere 36: 189–193. [Google Scholar]
  • 47. Schüppel KF, Reinacher M, Lebelt J, Kulka D (1995) Bornasche Krankheit bei Primaten. Verh ber Erkrg Zootiere 37: 115–119. [Google Scholar]
  • 48. Solbrig MV, Fallon JH, Lipkin WI (1995) Behavioral disturbances and pharmacology of Borna disease. Curr Top Microbiol Immunol 190: 93–102. [DOI] [PubMed] [Google Scholar]
  • 49. Stitz L, Dietzschold B, Carbone KM (1995) Immunopathogenesis of Borna disease. Curr Top Microbiol Immunol 190: 75–92. [DOI] [PubMed] [Google Scholar]
  • 50. Stitz L, Schilken D, Frese K (1991) Atypical dissemination of highly neurotropic Borna disease virus during persistent infection of cyclosporine A‐treated immunosuppressed rats. J Virol 65: 457–460. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 51. Teng MN, Borrow P, Oldstone MB, De‐la‐Torre JC (1996) A single amino acid change in the glycoprotein of lymphocytic choriomeningits virus is associated with the ability to cause growth hormone deficiency syndrome. J Virol 70: 8438–8443. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 52. Villarette L, Somasundaram T, Ahmed R (1994) Tissue‐mediated selection of viral variants: correlation between glycoprotein mutation and growth in neuronal cells. J Virol 68: 7490–7496. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 53. Waltrip RW 2nd, Buchanan RW, Carpenter WT Jr, Kirkpatrick B, Summerfelt A, Breier A, Rubin SA, Carbone KM (1997) Borna disease virus antibodies and the deficit syndrome of schizophrenia. Schizophr Res 23: 253–257. [DOI] [PubMed] [Google Scholar]
  • 54. Weissenböck H, Novotny N, Caplazi P, Kolodziejek J, Ehrensperger F (1998) Borna disease in a dog with letal meningoencephalitis. J Clin Microbiol 36: 2127–2130. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 55. Wilding JPH, Gilbey SG, Bailey CJ, Batt RAL, Williams G, Ghatei MA, Bloom SR (1993) Increased neuropeptide Y messenger ribonucleic acid (mRNA) and decreased neurotensin mRNA in the hypothalamus of the obese (ob/ob) mouse. Endocrinology 132: 1939–1944. [DOI] [PubMed] [Google Scholar]
  • 56. Williams G, Steel JH, Cardoso H, Ghatei MA, Lee YC, Gill JS, Burrin JM, Polak JM, Bloom SR (1988) Increased hypothalamic neuropeptide Y concentrations in diabetic rats. Diabetes 37: 763–772. [DOI] [PubMed] [Google Scholar]
  • 57. Ye X, Carp RI, Kozielski R, Kozlowski P (1994) Effect of infection with the 139H scrapie strain on the number, area and/or location of hypothalamic CRF‐ and VP‐immunostained neurons. Acta Neuropathol 88: 44–54. [DOI] [PubMed] [Google Scholar]
  • 58. Zwick W, (1939) Bornasche Krankheit und Encephalomyelitis der Tiere In: Handbuch der Viruskrankheiten, Gildemeister E, Haagen E, Waldmann O (eds), pp. 252–354, G. Fischer: Jena . [Google Scholar]

Articles from Brain Pathology are provided here courtesy of Wiley

RESOURCES