Medicine:Borna disease

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Borna disease viruses 1 and 2
SpecialtyVeterinary medicine
Borna disease virus
Virus classification e
(unranked): Virus
Realm: Riboviria
Kingdom: Orthornavirae
Phylum: Negarnaviricota
Class: Monjiviricetes
Order: Mononegavirales
Family: Bornaviridae
Genus: Orthobornavirus
Mammalian 1 orthobornavirus
  • Borna disease virus 1
  • Borna disease virus 2

Borna disease, also known as sad horse disease,[1] is an infectious neurological syndrome[2] of warm-blooded animals, caused by Borna disease viruses 1 and 2 (BoDV-1/2). BoDV-1/2 are neurotropic viruses of the species Mammalian 1 orthobornavirus, and members of the Bornaviridae family within the Mononegavirales order.

Borna disease is a severe neurological illness that predominantly affects horses and sheep, but it has been observed in a wide range of mammals. The disease is characterised by ataxia and abnormal depressive behaviour, frequently culminating in death. There have been rare cases of human fatalities associated with encephalitis caused by Borna disease virus infection.[3] Additionally, correlative evidence exists linking BoDV-1/2 infection with neuropsychiatric disorders such as bipolar disorder in humans.[4]


Borna disease was first described in 1885, when all horses belonging to a cavalry regiment stationed near the city of Borna in Saxony, Germany, died from a hitherto unknown disease, then termed hitzige Kopfkrankheit ("hot-tempered head illness"). In 1909, Ernst Joest and Kurt Degen discovered distinctive inclusions in the nerves of horses that had died of Borna disease, which were named Joest-Degen inclusion bodies.[5] This histopathological feature remains in use today to confirm the presence of Borna disease. In 1924, the Austrian virologist Wilhelm Zwick suggested a virus as the cause of the disease.[citation needed]


The mode of transmission of BoDV-1/2 is unclear but probably occurs through intranasal exposure to contaminated saliva or nasal secretions. Following infection, individuals may develop Borna disease, or may remain subclinical, possibly acting as a carrier of the virus.[citation needed] The only known animal reservoir of BoDV-1 is the bicolored shrew (Crocidura leucodon), which is not susceptible to Borna disease.[6] It is unclear whether human or livestock infections are due to zoonotic transmission from the bicolored shrew.

Disease in animals


Borna diseases viruses 1 and 2 appear to have wide host ranges, having been detected in horses, cattle, sheep, new world camelids, dogs, cats, and foxes.[7][8] In 1995, BoDV-1 was isolated from cats with a "staggering disease" in Sweden.[9] BoDV-1 has been detected in animals in Europe, Asia, Africa and North America.[citation needed]

Symptoms of Borna disease in horses and sheep start after a four-week incubation period followed by the development of immune-mediated meningitis and encephalomyelitis.[citation needed] Clinical manifestations vary but may include excited or depressed behaviour, ataxia, teeth grinding, excessive salivating, ocular disorders and abnormal posture and movement. Later stages are characterised by bouts of fever and flailing of limbs while lying down. Death occurs a few days to weeks after symptom onset. Mortality rates are 80-100% in horses and greater than 50% in sheep.[citation needed]

Experimental infection of rats has been demonstrated to lead to learning impairments and altered social behaviour. The virus appears to be distributed primarily in the limbic system of the brain, including the hippocampus and entorhinal cortex. These areas of the brain are considered to be of importance in emotion.[citation needed]


Avian bornaviruses, a group of related viruses, have been reported, yet not proven, as the cause of proventricular dilatation disease (PDD), a disease of pet parrots. The use of a 'positive' brain cell culture containing ABV to inoculate another psittacine (parrot) bird resulted in the inoculated bird's death and subsequent histopathological diagnosis of PDD (mononuclear infiltrative ganglioneuritis). Earlier research with purified avian bornavirus inoculant (while did result in the death of parrots) did not reproduce histopathological changes associated with PDD.[citation needed]

Disease in humans

Antibodies to BoDV-1 in humans were first discovered in the mid-1980s, suggesting that humans can be non-fatally infected. Antibodies to BoDV-1 and BoDV-1 antigen have also been detected in blood donors.[citation needed]


In 2018, three fatal cases of Borna disease in humans were confirmed in Germany.[10][11] Three people were suspected to have been infected via organ transplants from the same donor, two of whom died. A third fatal case was unconnected to the organ donation. All three deaths were due to severe encephalitis.[10][11]

In 2020, several additional cases of human infection were identified in the German federal state of Bavaria.[12] In total, there have been 24 cases of confirmed BoDV-1 infection of humans between 1996 and 2021 [citation needed]. The infection was almost always fatal. All cases occurred in known areas of spread of BoDV-1, including the federal states of Bavaria, Brandenburg, Thuringia, and Saxony-Anhalt.[3][13][14][15][16][17][18][19][20][21][22][excessive citations]

Psychiatric disease

There is some evidence that there may be a relationship between BoDV-1 infection and psychiatric disease.[4][23]

In 1990, Janice E. Clements and colleagues reported in the journal Science that antibodies to a protein encoded by the BoDV-1 genome are found in the blood of patients with behavioral disorders.[24] In the early 1990s, researchers in Germany, America, and Japan conducted an investigation of 5000 patients with psychiatric disorders and 1000 controls, in which a significantly higher percentage of patients than controls were positive for BoDV-1 antibodies.[24] Subsequent studies have also presented evidence for an association between BoDV-1 and human psychiatric disorders.[25][26][27] However, not all researchers consider the link between BoDV-1 and human psychiatric disease to be conclusively proven. A study published in 2003 found no BoDV-1 antibodies in 62 patients with the deficit form of schizophrenia.[28]

Additional evidence for a role of BoDV-1 in psychiatric disorders comes from reports that the drug amantadine, which is used to treat influenza infections, has had some success in treating depression and clearing BoDV-1 infection.[29][30]


  1. "Sad horse disease" (in en), A Dictionary of Psychology (Oxford University Press), 2009-01-01, doi:10.1093/acref/9780199534067.001.0001, ISBN 978-0-19-953406-7,, retrieved 2020-01-16 
  2. "Adaptation of Borna disease virus to new host species attributed to altered regulation of viral polymerase activity". Journal of Virology 81 (15): 7933–7940. August 2007. doi:10.1128/JVI.00334-07. PMID 17522214. 
  3. 3.0 3.1 "Zoonotic spillover infections with Borna disease virus 1 leading to fatal human encephalitis, 1999-2019: an epidemiological investigation". The Lancet. Infectious Diseases 20 (4): 467–477. April 2020. doi:10.1016/s1473-3099(19)30546-8. PMID 31924550. 
  4. 4.0 4.1 "Borna disease virus infection, a human mental-health risk". Clinical Microbiology Reviews 16 (3): 534–545. July 2003. doi:10.1128/CMR.16.3.534-545.2003. PMID 12857781. 
  5. "Über eigentümliche Kerneinschlüsse der Ganglienzellen bei der enzootischen Gehirn-Rückenmarksentzündung der Pferde". Zeitschrift Infekt. Der Haustiere 6: 348–356. 1909. 
  6. "The bicolored white-toothed shrew Crocidura leucodon (HERMANN 1780) is an indigenous host of mammalian Borna disease virus". PLOS ONE 9 (4): e93659. April 2014. doi:10.1371/journal.pone.0093659. PMID 24699636. Bibcode2014PLoSO...993659D. 
  7. "New World camelids are sentinels for the presence of Borna disease virus". Transboundary and Emerging Diseases 69 (2): 451–464. March 2022. doi:10.1111/tbed.14003. PMID 33501762. 
  8. "Borna disease: current knowledge and virus detection in France". Veterinary Research 33 (2): 127–138. 2002. doi:10.1051/vetres:2002002. PMID 11944803. 
  9. "Borna disease virus (BDV) infection in cats. A concise review based on current knowledge". The Veterinary Quarterly 28 (2): 66–73. June 2006. doi:10.1080/01652176.2006.9695210. PMID 16841569. 
  10. 10.0 10.1 "Three deaths in Germany: Borna virus dangerous to humans after all". 2018-03-27. 
  11. 11.0 11.1 "Human Infection with Borna Disease Virus (BoDV-1)". Online Focus. Robert-Koch-Institut. 2018-03-08. 
  12. "Alle Borna-Erkrankten lebten auf dem Land". 2020-11-25. 
  13. "Human Borna disease virus 1 (BoDV-1) encephalitis cases in the north and east of Germany". Emerging Microbes & Infections 11 (1): 6–13. December 2022. doi:10.1080/22221751.2021.2007737. PMID 34783638. 
  14. "Investigation of fatal human Borna disease virus 1 encephalitis outside the previously known area for human cases, Brandenburg, Germany - a case report". BMC Infectious Diseases 21 (1): 787. August 2021. doi:10.1186/s12879-021-06439-3. PMID 34376142. 
  15. "Active Case Finding of Current Bornavirus Infections in Human Encephalitis Cases of Unknown Etiology, Germany, 2018-2020" (in en-us). Emerging Infectious Diseases 27 (5): 1371–1379. May 2021. doi:10.3201/eid2705.204490. PMID 33900167. 
  16. "The neuropathology of fatal encephalomyelitis in human Borna virus infection". Acta Neuropathologica 138 (4): 653–665. October 2019. doi:10.1007/s00401-019-02047-3. PMID 31346692. 
  17. "Fatal Encephalitic Borna Disease Virus 1 in Solid-Organ Transplant Recipients". The New England Journal of Medicine 379 (14): 1377–1379. October 2018. doi:10.1056/NEJMc1803115. PMID 30281984. 
  18. "Hemorrhagic lesion with detection of infected endothelial cells in human bornavirus encephalitis". Acta Neuropathologica 144 (2): 377–379. June 2022. doi:10.1007/s00401-022-02442-3. PMID 35657496. 
  19. "Antibodies against viral nucleo-, phospho-, and X protein contribute to serological diagnosis of fatal Borna disease virus 1 infections". Cell Reports. Medicine 3 (1): 100499. January 2022. doi:10.1016/j.xcrm.2021.100499. PMID 35106511. 
  20. "[Bornavirus encephalitis as a differential diagnosis to seronegative autoimmune encephalitis"] (in de). Der Nervenarzt 93 (8): 835–837. January 2022. doi:10.1007/s00115-021-01259-x. PMID 35024881. 
  21. "Fatal Encephalitis Associated with Borna Disease Virus 1". The New England Journal of Medicine 379 (14): 1375–1377. October 2018. doi:10.1056/NEJMc1800724. PMID 30281979. 
  22. "Severe bornavirus-encephalitis presenting as Guillain-Barré-syndrome". Acta Neuropathologica 137 (6): 1017–1019. June 2019. doi:10.1007/s00401-019-02005-z. PMID 30953131. 
  23. "A borna virus cDNA encoding a protein recognized by antibodies in humans with behavioral diseases". Science 250 (4985): 1278–1281. November 1990. doi:10.1126/science.2244211. PMID 2244211. Bibcode1990Sci...250.1278V. 
  24. 24.0 24.1 "Borna disease, a possible hazard for man?". Archives of Virology 118 (3–4): 143–149. 1991. doi:10.1007/BF01314025. PMID 2069502. 
  25. "Detection of Borna disease virus p24 RNA in peripheral blood cells from Brazilian mood and psychotic disorder patients". Journal of Affective Disorders 90 (1): 43–47. January 2006. doi:10.1016/j.jad.2005.10.008. PMID 16324750. 
  26. "Immunological and PCR analyses for Borna disease virus in psychiatric patients and blood donors in Japan". Journal of Clinical Microbiology 39 (2): 419–429. February 2001. doi:10.1128/JCM.39.2.419-429.2001. PMID 11158085. 
  27. "Borna disease virus antibodies and the deficit syndrome of schizophrenia". Schizophrenia Research 23 (3): 253–257. February 1997. doi:10.1016/S0920-9964(96)00114-4. PMID 9075304. 
  28. "Borna disease virus and deficit schizophrenia". Acta Neuropsychiatrica 15 (5): 262–265. October 2003. doi:10.1034/j.1601-5215.2003.00043.x. PMID 26983654. 
  29. "Amantadine in depressive patients with Borna disease virus (BDV) infection: an open trial". Bipolar Disorders 2 (1): 65–70. March 2000. doi:10.1034/j.1399-5618.2000.020110.x. PMID 11254023. 
  30. Thakur, R; Sarma, S; Sharma, B (2009). "Role of Borna Disease Virus in Neuropsychiatric Illnesses: Are We Inching Closer?". Indian Journal of Medical Microbiology (Elsevier BV) 27 (3): 191–201. doi:10.4103/0255-0857.53200. ISSN 0255-0857. PMID 19584498. 

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