Skip to main content
Emerging Infectious Diseases logoLink to Emerging Infectious Diseases
. 1997 Apr-Jun;3(2):129–135. doi: 10.3201/eid0302.970205

Borna disease.

C G Hatalski 1, A J Lewis 1, W I Lipkin 1
PMCID: PMC2627619  PMID: 9204293

Abstract

Borna disease virus, a newly classified nonsegmented negative-strand RNA virus with international distribution, infects a broad range of warm-blooded animals from birds to primates. Infection causes movement and behavioral disturbances reminiscent of some neuropsychiatric syndromes. The virus has not been clearly linked to any human disease; however, an association between infection with the virus and selected neuropsychiatric disorders has been suggested. We reviewed recent advances in Borna disease virus research, focusing on evidence of infection in humans.

Full Text

The Full Text of this article is available as a PDF (35.8 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Amsterdam J. D., Winokur A., Dyson W., Herzog S., Gonzalez F., Rott R., Koprowski H. Borna disease virus. A possible etiologic factor in human affective disorders? Arch Gen Psychiatry. 1985 Nov;42(11):1093–1096. doi: 10.1001/archpsyc.1985.01790340077011. [DOI] [PubMed] [Google Scholar]
  2. Bautista J. R., Rubin S. A., Moran T. H., Schwartz G. J., Carbone K. M. Developmental injury to the cerebellum following perinatal Borna disease virus infection. Brain Res Dev Brain Res. 1995 Dec 21;90(1-2):45–53. doi: 10.1016/0165-3806(96)83485-7. [DOI] [PubMed] [Google Scholar]
  3. Bautista J. R., Schwartz G. J., De La Torre J. C., Moran T. H., Carbone K. M. Early and persistent abnormalities in rats with neonatally acquired Borna disease virus infection. Brain Res Bull. 1994;34(1):31–40. doi: 10.1016/0361-9230(94)90183-x. [DOI] [PubMed] [Google Scholar]
  4. Bechter K., Bauer M., Estler H. C., Herzog S., Schüttler R., Rott R. Erweiterte kernspintomographische Untersuchungen bei Borna-disease-Virus -seropositiven psychiatrischen Patienten und Kontrollen. Nervenarzt. 1994 Mar;65(3):169–174. [PubMed] [Google Scholar]
  5. Bechter K., Schüttler R., Herzog S. Case of neurological and behavioral abnormalities: due to Borna disease virus encephalitis? Psychiatry Res. 1992 May;42(2):193–196. doi: 10.1016/0165-1781(92)90083-f. [DOI] [PubMed] [Google Scholar]
  6. Binz T., Lebelt J., Niemann H., Hagenau K. Sequence analyses of the p24 gene of Borna disease virus in naturally infected horse, donkey and sheep. Virus Res. 1994 Dec;34(3):281–289. doi: 10.1016/0168-1702(94)90128-7. [DOI] [PubMed] [Google Scholar]
  7. Bode L., Dürrwald R., Rantam F. A., Ferszt R., Ludwig H. First isolates of infectious human Borna disease virus from patients with mood disorders. Mol Psychiatry. 1996 Jul;1(3):200–212. [PubMed] [Google Scholar]
  8. Bode L., Ferszt R., Czech G. Borna disease virus infection and affective disorders in man. Arch Virol Suppl. 1993;7:159–167. doi: 10.1007/978-3-7091-9300-6_13. [DOI] [PubMed] [Google Scholar]
  9. Bode L. Human infections with Borna disease virus and potential pathogenic implications. Curr Top Microbiol Immunol. 1995;190:103–130. doi: 10.1007/978-3-642-78618-1_7. [DOI] [PubMed] [Google Scholar]
  10. Bode L., Riegel S., Lange W., Ludwig H. Human infections with Borna disease virus: seroprevalence in patients with chronic diseases and healthy individuals. J Med Virol. 1992 Apr;36(4):309–315. doi: 10.1002/jmv.1890360414. [DOI] [PubMed] [Google Scholar]
  11. Bode L., Riegel S., Ludwig H., Amsterdam J. D., Lange W., Koprowski H. Borna disease virus-specific antibodies in patients with HIV infection and with mental disorders. Lancet. 1988 Sep 17;2(8612):689–689. doi: 10.1016/s0140-6736(88)90505-3. [DOI] [PubMed] [Google Scholar]
  12. Bode L., Steinbach F., Ludwig H. A novel marker for Borna disease virus infection. Lancet. 1994 Jan 29;343(8892):297–298. doi: 10.1016/s0140-6736(94)91147-9. [DOI] [PubMed] [Google Scholar]
  13. Bode L., Zimmermann W., Ferszt R., Steinbach F., Ludwig H. Borna disease virus genome transcribed and expressed in psychiatric patients. Nat Med. 1995 Mar;1(3):232–236. doi: 10.1038/nm0395-232. [DOI] [PubMed] [Google Scholar]
  14. Briese T., Schneemann A., Lewis A. J., Park Y. S., Kim S., Ludwig H., Lipkin W. I. Genomic organization of Borna disease virus. Proc Natl Acad Sci U S A. 1994 May 10;91(10):4362–4366. doi: 10.1073/pnas.91.10.4362. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Briese T., de la Torre J. C., Lewis A., Ludwig H., Lipkin W. I. Borna disease virus, a negative-strand RNA virus, transcribes in the nucleus of infected cells. Proc Natl Acad Sci U S A. 1992 Dec 1;89(23):11486–11489. doi: 10.1073/pnas.89.23.11486. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Carbone K. M., Duchala C. S., Griffin J. W., Kincaid A. L., Narayan O. 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. 1987 Nov;61(11):3431–3440. doi: 10.1128/jvi.61.11.3431-3440.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Carbone K. M., Park S. W., Rubin S. A., Waltrip R. W., 2nd, Vogelsang G. B. Borna disease: association with a maturation defect in the cellular immune response. J Virol. 1991 Nov;65(11):6154–6164. doi: 10.1128/jvi.65.11.6154-6164.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Cubitt B., Oldstone C., Valcarcel J., Carlos de la Torre J. RNA splicing contributes to the generation of mature mRNAs of Borna disease virus, a non-segmented negative strand RNA virus. Virus Res. 1994 Oct;34(1):69–79. doi: 10.1016/0168-1702(94)90120-1. [DOI] [PubMed] [Google Scholar]
  19. Cubitt B., Oldstone C., de la Torre J. C. Sequence and genome organization of Borna disease virus. J Virol. 1994 Mar;68(3):1382–1396. doi: 10.1128/jvi.68.3.1382-1396.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. De La Torre J. C., Gonzalez-Dunia D., Cubitt B., Mallory M., Mueller-Lantzsch N., Grässer F. A., Hansen L. A., Masliah E. Detection of borna disease virus antigen and RNA in human autopsy brain samples from neuropsychiatric patients. Virology. 1996 Sep 15;223(2):272–282. doi: 10.1006/viro.1996.0479. [DOI] [PubMed] [Google Scholar]
  21. Dittrich W., Bode L., Ludwig H., Kao M., Schneider K. Learning deficiencies in Borna disease virus-infected but clinically healthy rats. Biol Psychiatry. 1989 Dec;26(8):818–828. doi: 10.1016/0006-3223(89)90122-4. [DOI] [PubMed] [Google Scholar]
  22. Fu Z. F., Amsterdam J. D., Kao M., Shankar V., Koprowski H., Dietzschold B. Detection of Borna disease virus-reactive antibodies from patients with affective disorders by western immunoblot technique. J Affect Disord. 1993 Jan;27(1):61–68. doi: 10.1016/0165-0327(93)90098-5. [DOI] [PubMed] [Google Scholar]
  23. Gosztonyi G., Ludwig H. Borna disease--neuropathology and pathogenesis. Curr Top Microbiol Immunol. 1995;190:39–73. [PubMed] [Google Scholar]
  24. Holland J. J., De La Torre J. C., Steinhauer D. A. RNA virus populations as quasispecies. Curr Top Microbiol Immunol. 1992;176:1–20. doi: 10.1007/978-3-642-77011-1_1. [DOI] [PubMed] [Google Scholar]
  25. Holland J., Spindler K., Horodyski F., Grabau E., Nichol S., VandePol S. Rapid evolution of RNA genomes. Science. 1982 Mar 26;215(4540):1577–1585. doi: 10.1126/science.7041255. [DOI] [PubMed] [Google Scholar]
  26. Igata-Yi R., Yamaguchi K., Yoshiki K., Takemoto S., Yamasaki H., Matsuoka M., Miyakawa T. Borna disease virus and the consumption of raw horse meat. Nat Med. 1996 Sep;2(9):948–949. doi: 10.1038/nm0996-948b. [DOI] [PubMed] [Google Scholar]
  27. Kao M., Hamir A. N., Rupprecht C. E., Fu Z. F., Shankar V., Koprowski H., Dietzschold B. Detection of antibodies against Borna disease virus in sera and cerebrospinal fluid of horses in the USA. Vet Rec. 1993 Mar 6;132(10):241–244. doi: 10.1136/vr.132.10.241. [DOI] [PubMed] [Google Scholar]
  28. Kishi M., Arimura Y., Ikuta K., Shoya Y., Lai P. K., Kakinuma M. Sequence variability of Borna disease virus open reading frame II found in human peripheral blood mononuclear cells. J Virol. 1996 Jan;70(1):635–640. doi: 10.1128/jvi.70.1.635-640.1996. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Kishi M., Nakaya T., Nakamura Y., Kakinuma M., Takahashi T. A., Sekiguchi S., Uchikawa M., Tadokoro K., Ikeda K., Ikuta K. Prevalence of Borna disease virus RNA in peripheral blood mononuclear cells from blood donors. Med Microbiol Immunol. 1995 Oct;184(3):135–138. doi: 10.1007/BF00224350. [DOI] [PubMed] [Google Scholar]
  30. Kishi M., Nakaya T., Nakamura Y., Zhong Q., Ikeda K., Senjo M., Kakinuma M., Kato S., Ikuta K. Demonstration of human Borna disease virus RNA in human peripheral blood mononuclear cells. FEBS Lett. 1995 May 15;364(3):293–297. doi: 10.1016/0014-5793(95)00406-y. [DOI] [PubMed] [Google Scholar]
  31. Lipkin W. I., Travis G. H., Carbone K. M., Wilson M. C. Isolation and characterization of Borna disease agent cDNA clones. Proc Natl Acad Sci U S A. 1990 Jun;87(11):4184–4188. doi: 10.1073/pnas.87.11.4184. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Ludwig H., Bode L., Gosztonyi G. Borna disease: a persistent virus infection of the central nervous system. Prog Med Virol. 1988;35:107–151. [PubMed] [Google Scholar]
  33. Lundgren A. L., Czech G., Bode L., Ludwig H. Natural Borna disease in domestic animals others than horses and sheep. Zentralbl Veterinarmed B. 1993 Jun;40(4):298–303. doi: 10.1111/j.1439-0450.1993.tb00142.x. [DOI] [PubMed] [Google Scholar]
  34. Morales J. A., Herzog S., Kompter C., Frese K., Rott R. Axonal transport of Borna disease virus along olfactory pathways in spontaneously and experimentally infected rats. Med Microbiol Immunol. 1988;177(2):51–68. doi: 10.1007/BF00189527. [DOI] [PubMed] [Google Scholar]
  35. Nakamura Y., Asahi S., Nakaya T., Bahmani M. K., Saitoh S., Yasui K., Mayama H., Hagiwara K., Ishihara C., Ikuta K. Demonstration of borna disease virus RNA in peripheral blood mononuclear cells derived from domestic cats in Japan. J Clin Microbiol. 1996 Jan;34(1):188–191. doi: 10.1128/jcm.34.1.188-191.1996. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Nakamura Y., Kishi M., Nakaya T., Asahi S., Tanaka H., Sentsui H., Ikeda K., Ikuta K. Demonstration of Borna disease virus RNA in peripheral blood mononuclear cells from healthy horses in Japan. Vaccine. 1995 Aug;13(12):1076–1079. doi: 10.1016/0264-410x(95)00050-b. [DOI] [PubMed] [Google Scholar]
  37. Nakaya T., Takahashi H., Nakamura Y., Asahi S., Tobiume M., Kuratsune H., Kitani T., Yamanishi K., Ikuta K. Demonstration of Borna disease virus RNA in peripheral blood mononuclear cells derived from Japanese patients with chronic fatigue syndrome. FEBS Lett. 1996 Jan 8;378(2):145–149. doi: 10.1016/0014-5793(95)01439-x. [DOI] [PubMed] [Google Scholar]
  38. Narayan O., Herzog S., Frese K., Scheefers H., Rott R. Behavioral disease in rats caused by immunopathological responses to persistent borna virus in the brain. Science. 1983 Jun 24;220(4604):1401–1403. doi: 10.1126/science.6602380. [DOI] [PubMed] [Google Scholar]
  39. Richt J. A., VandeWoude S., Zink M. C., Clements J. E., Herzog S., Stitz L., Rott R., Narayan O. Infection with Borna disease virus: molecular and immunobiological characterization of the agent. Clin Infect Dis. 1992 Jun;14(6):1240–1250. doi: 10.1093/clinids/14.6.1240. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Rott R., Becht H. Natural and experimental Borna disease in animals. Curr Top Microbiol Immunol. 1995;190:17–30. doi: 10.1007/978-3-642-78618-1_2. [DOI] [PubMed] [Google Scholar]
  41. Rott R., Herzog S., Bechter K., Frese K. Borna disease, a possible hazard for man? Arch Virol. 1991;118(3-4):143–149. doi: 10.1007/BF01314025. [DOI] [PubMed] [Google Scholar]
  42. Rott R., Herzog S., Fleischer B., Winokur A., Amsterdam J., Dyson W., Koprowski H. Detection of serum antibodies to Borna disease virus in patients with psychiatric disorders. Science. 1985 May 10;228(4700):755–756. doi: 10.1126/science.3922055. [DOI] [PubMed] [Google Scholar]
  43. Sauder C., Müller A., Cubitt B., Mayer J., Steinmetz J., Trabert W., Ziegler B., Wanke K., Mueller-Lantzsch N., de la Torre J. C. 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. 1996 Nov;70(11):7713–7724. doi: 10.1128/jvi.70.11.7713-7724.1996. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. Schneemann A., Schneider P. A., Kim S., Lipkin W. I. Identification of signal sequences that control transcription of borna disease virus, a nonsegmented, negative-strand RNA virus. J Virol. 1994 Oct;68(10):6514–6522. doi: 10.1128/jvi.68.10.6514-6522.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. Schneemann A., Schneider P. A., Lamb R. A., Lipkin W. I. The remarkable coding strategy of borna disease virus: a new member of the nonsegmented negative strand RNA viruses. Virology. 1995 Jun 20;210(1):1–8. doi: 10.1006/viro.1995.1311. [DOI] [PubMed] [Google Scholar]
  46. Schneider P. A., Briese T., Zimmermann W., Ludwig H., Lipkin W. I. Sequence conservation in field and experimental isolates of Borna disease virus. J Virol. 1994 Jan;68(1):63–68. doi: 10.1128/jvi.68.1.63-68.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  47. Schneider P. A., Schneemann A., Lipkin W. I. RNA splicing in Borna disease virus, a nonsegmented, negative-strand RNA virus. J Virol. 1994 Aug;68(8):5007–5012. doi: 10.1128/jvi.68.8.5007-5012.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  48. Sierra-Honigmann A. M., Carbone K. M., Yolken R. H. Polymerase chain reaction (PCR) search for viral nucleic acid sequences in schizophrenia. Br J Psychiatry. 1995 Jan;166(1):55–60. doi: 10.1192/bjp.166.1.55. [DOI] [PubMed] [Google Scholar]
  49. Sierra-Honigmann A. M., Rubin S. A., Estafanous M. G., Yolken R. H., Carbone K. M. Borna disease virus in peripheral blood mononuclear and bone marrow cells of neonatally and chronically infected rats. J Neuroimmunol. 1993 Jun;45(1-2):31–36. doi: 10.1016/0165-5728(93)90160-z. [DOI] [PubMed] [Google Scholar]
  50. Solbrig M. V., Fallon J. H., Lipkin W. I. Behavioral disturbances and pharmacology of Borna disease. Curr Top Microbiol Immunol. 1995;190:93–101. doi: 10.1007/978-3-642-78618-1_6. [DOI] [PubMed] [Google Scholar]
  51. Solbrig M. V., Koob G. F., Joyce J. N., Lipkin W. I. A neural substrate of hyperactivity in borna disease: changes in brain dopamine receptors. Virology. 1996 Aug 15;222(2):332–338. doi: 10.1006/viro.1996.0430. [DOI] [PubMed] [Google Scholar]
  52. Sprankel H., Richarz K., Ludwig H., Rott R. Behavior alterations in tree shrews (Tupaia glis, Diard 1820) induced by Borna disease virus. Med Microbiol Immunol. 1978 May 26;165(1):1–18. doi: 10.1007/BF02121228. [DOI] [PubMed] [Google Scholar]
  53. Stitz L., Dietzschold B., Carbone K. M. Immunopathogenesis of Borna disease. Curr Top Microbiol Immunol. 1995;190:75–92. doi: 10.1007/978-3-642-78618-1_5. [DOI] [PubMed] [Google Scholar]
  54. Stitz L., Krey H., Ludwig H. Borna disease in rhesus monkeys as a models for uveo-cerebral symptoms. J Med Virol. 1981;6(4):333–340. doi: 10.1002/jmv.1890060408. [DOI] [PubMed] [Google Scholar]
  55. Waltrip R. W., 2nd, Buchanan R. W., Summerfelt A., Breier A., Carpenter W. T., Jr, Bryant N. L., Rubin S. A., Carbone K. M. Borna disease virus and schizophrenia. Psychiatry Res. 1995 Jan 31;56(1):33–44. doi: 10.1016/0165-1781(94)02600-n. [DOI] [PubMed] [Google Scholar]
  56. Yolken R. H., Torrey E. F. Viruses, schizophrenia, and bipolar disorder. Clin Microbiol Rev. 1995 Jan;8(1):131–145. doi: 10.1128/cmr.8.1.131. [DOI] [PMC free article] [PubMed] [Google Scholar]
  57. de la Torre J. C., Bode L., Dürrwald R., Cubitt B., Ludwig H. Sequence characterization of human Borna disease virus. Virus Res. 1996 Sep;44(1):33–44. doi: 10.1016/0168-1702(96)01338-x. [DOI] [PubMed] [Google Scholar]
  58. de la Torre J. C. Molecular biology of borna disease virus: prototype of a new group of animal viruses. J Virol. 1994 Dec;68(12):7669–7675. doi: 10.1128/jvi.68.12.7669-7675.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Emerging Infectious Diseases are provided here courtesy of Centers for Disease Control and Prevention

RESOURCES