Misplaced Pages

Borna disease virus
Virus classification
(unranked):	Virus
Realm:	Riboviria
Kingdom:	Orthornavirae
Phylum:	Negarnaviricota
Class:	Monjiviricetes
Order:	Mononegavirales
Family:	Bornaviridae
Genus:	Orthobornavirus
Species:	Mammalian 1 orthobornavirus
Subtypes
Borna disease virus 1 Borna disease virus 2

Borna disease, also known as sad horse disease, is an infectious neurological syndrome 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. Additionally, correlative evidence exists linking BoDV-1/2 infection with neuropsychiatric disorders such as bipolar disorder in humans.

History

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. 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.

Transmission

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. The only known animal reservoir of BoDV-1 is the bicolored shrew (Crocidura leucodon), which is not susceptible to Borna disease. It is unclear whether human or livestock infections are due to zoonotic transmission from the bicolored shrew.

Disease in animals

Mammals

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. In 1995, BoDV-1 was isolated from cats with a "staggering disease" in Sweden. BoDV-1 has been detected in animals in Europe, Asia, Africa and North America.

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. 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.

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.

Birds

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.

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.

Encephalitis

In 2018, three fatal cases of Borna disease in humans were confirmed in Germany. 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.

In 2020, several additional cases of human infection were identified in the German federal state of Bavaria. In total, there have been 24 cases of confirmed BoDV-1 infection of humans between 1996 and 2021 . 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.

Psychiatric disease

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

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. 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. Subsequent studies have also presented evidence for an association between BoDV-1 and human psychiatric disorders. 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.

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.

References

1. Colman AM (2009-01-01), "Sad horse disease", A Dictionary of Psychology, Oxford University Press, doi:10.1093/acref/9780199534067.001.0001, ISBN 978-0-19-953406-7, retrieved 2020-01-16
2. Ackermann A, Staeheli P, Schneider U (August 2007). "Adaptation of Borna disease virus to new host species attributed to altered regulation of viral polymerase activity". Journal of Virology. 81 (15): 7933–7940. doi:10.1128/JVI.00334-07. PMC 1951315. PMID 17522214.
3. ^ Niller HH, Angstwurm K, Rubbenstroth D, Schlottau K, Ebinger A, Giese S, et al. (April 2020). "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. doi:10.1016/s1473-3099(19)30546-8. PMID 31924550. S2CID 210149895.
4. ^ Bode L, Ludwig H (July 2003). "Borna disease virus infection, a human mental-health risk". Clinical Microbiology Reviews. 16 (3): 534–545. doi:10.1128/CMR.16.3.534-545.2003. PMC 164222. PMID 12857781.
5. Joest E, Degen K (1909). "Über eigentümliche Kerneinschlüsse der Ganglienzellen bei der enzootischen Gehirn-Rückenmarksentzündung der Pferde". Zeitschrift Infekt. Der Haustiere. 6: 348–356.
6. Dürrwald R, Kolodziejek J, Weissenböck H, Nowotny N (April 2014). "The bicolored white-toothed shrew Crocidura leucodon (HERMANN 1780) is an indigenous host of mammalian Borna disease virus". PLOS ONE. 9 (4): e93659. Bibcode:2014PLoSO...993659D. doi:10.1371/journal.pone.0093659. PMC 3974811. PMID 24699636.
7. Malbon AJ, Dürrwald R, Kolodziejek J, Nowotny N, Kobera R, Pöhle D, et al. (March 2022). "New World camelids are sentinels for the presence of Borna disease virus". Transboundary and Emerging Diseases. 69 (2): 451–464. doi:10.1111/tbed.14003. hdl:20.500.11820/4d648703-e060-4d23-a034-ac1131d3d648. PMID 33501762. S2CID 231756716.
8. Dauphin G, Legay V, Pitel PH, Zientara S (2002). "Borna disease: current knowledge and virus detection in France". Veterinary Research. 33 (2): 127–138. doi:10.1051/vetres:2002002. PMID 11944803.
9. Kamhieh S, Flower RL (June 2006). "Borna disease virus (BDV) infection in cats. A concise review based on current knowledge". The Veterinary Quarterly. 28 (2): 66–73. doi:10.1080/01652176.2006.9695210. PMID 16841569. S2CID 35691530.
10. ^ "Three deaths in Germany: Borna virus dangerous to humans after all". FOCUS Online. 2018-03-27. Retrieved 2022-06-09.
11. ^ "Human Infection with Borna Disease Virus (BoDV-1)" (PDF). Online Focus. Robert-Koch-Institut. 2018-03-08. Retrieved 2022-06-09.
12. "Alle Borna-Erkrankten lebten auf dem Land". n-tv.de. 2020-11-25. Retrieved 2022-06-09.
13. Frank C, Wickel J, Brämer D, Matschke J, Ibe R, Gazivoda C, et al. (December 2022). "Human Borna disease virus 1 (BoDV-1) encephalitis cases in the north and east of Germany". Emerging Microbes & Infections. 11 (1): 6–13. doi:10.1080/22221751.2021.2007737. PMC 8725967. PMID 34783638.
14. Tappe D, Pörtner K, Frank C, Wilking H, Ebinger A, Herden C, et al. (August 2021). "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. doi:10.1186/s12879-021-06439-3. PMC 8353434. PMID 34376142.
15. Eisermann P, Rubbenstroth D, Cadar D, Thomé-Bolduan C, Eggert P, Schlaphof A, et al. (May 2021). "Active Case Finding of Current Bornavirus Infections in Human Encephalitis Cases of Unknown Etiology, Germany, 2018-2020". Emerging Infectious Diseases. 27 (5): 1371–1379. doi:10.3201/eid2705.204490. PMC 8084505. PMID 33900167.
16. Liesche F, Ruf V, Zoubaa S, Kaletka G, Rosati M, Rubbenstroth D, et al. (October 2019). "The neuropathology of fatal encephalomyelitis in human Borna virus infection". Acta Neuropathologica. 138 (4): 653–665. doi:10.1007/s00401-019-02047-3. PMC 6778062. PMID 31346692.
17. Schlottau K, Forth L, Angstwurm K, Höper D, Zecher D, Liesche F, et al. (October 2018). "Fatal Encephalitic Borna Disease Virus 1 in Solid-Organ Transplant Recipients". The New England Journal of Medicine. 379 (14): 1377–1379. doi:10.1056/NEJMc1803115. PMID 30281984. S2CID 205064906.
18. Liesche-Starnecker F, Schifferer M, Schlegel J, Vollmuth Y, Rubbenstroth D, Delbridge C, et al. (June 2022). "Hemorrhagic lesion with detection of infected endothelial cells in human bornavirus encephalitis". Acta Neuropathologica. 144 (2): 377–379. doi:10.1007/s00401-022-02442-3. PMC 9164175. PMID 35657496.
19. Neumann B, Angstwurm K, Linker RA, Knoll G, Eidenschink L, Rubbenstroth D, et al. (January 2022). "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. doi:10.1016/j.xcrm.2021.100499. PMC 8784767. PMID 35106511.
20. Meier H, Bauer C, Finkenzeller W, Nentwich J, Städt M, Steininger P, et al. (January 2022). "[Bornavirus encephalitis as a differential diagnosis to seronegative autoimmune encephalitis]". Der Nervenarzt (in German). 93 (8): 835–837. doi:10.1007/s00115-021-01259-x. PMC 8756745. PMID 35024881.
21. Korn K, Coras R, Bobinger T, Herzog SM, Lücking H, Stöhr R, et al. (October 2018). "Fatal Encephalitis Associated with Borna Disease Virus 1". The New England Journal of Medicine. 379 (14): 1375–1377. doi:10.1056/NEJMc1800724. PMID 30281979. S2CID 52915090.
22. Coras R, Korn K, Kuerten S, Huttner HB, Ensser A (June 2019). "Severe bornavirus-encephalitis presenting as Guillain-Barré-syndrome". Acta Neuropathologica. 137 (6): 1017–1019. doi:10.1007/s00401-019-02005-z. PMID 30953131. S2CID 96450129.
23. VandeWoude S, Richt JA, Zink MC, Rott R, Narayan O, Clements JE (November 1990). "A borna virus cDNA encoding a protein recognized by antibodies in humans with behavioral diseases". Science. 250 (4985): 1278–1281. Bibcode:1990Sci...250.1278V. doi:10.1126/science.2244211. PMID 2244211.
24. ^ Rott R, Herzog S, Bechter K, Frese K (1991). "Borna disease, a possible hazard for man?". Archives of Virology. 118 (3–4): 143–149. doi:10.1007/BF01314025. PMID 2069502. S2CID 36530027.
25. Miranda HC, Nunes SO, Calvo ES, Suzart S, Itano EN, Watanabe MA (January 2006). "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. doi:10.1016/j.jad.2005.10.008. PMID 16324750.
26. Fukuda K, Takahashi K, Iwata Y, Mori N, Gonda K, Ogawa T, et al. (February 2001). "Immunological and PCR analyses for Borna disease virus in psychiatric patients and blood donors in Japan". Journal of Clinical Microbiology. 39 (2): 419–429. doi:10.1128/JCM.39.2.419-429.2001. PMC 87754. PMID 11158085.
27. Waltrip RW, Buchanan RW, Carpenter WT, Kirkpatrick B, Summerfelt A, Breier A, et al. (February 1997). "Borna disease virus antibodies and the deficit syndrome of schizophrenia". Schizophrenia Research. 23 (3): 253–257. doi:10.1016/S0920-9964(96)00114-4. PMID 9075304. S2CID 5761430.
28. Kim YK, Kim SH, Han CS, Lee HJ, Kim HS, Yoon SC, et al. (October 2003). "Borna disease virus and deficit schizophrenia". Acta Neuropsychiatrica. 15 (5): 262–265. doi:10.1034/j.1601-5215.2003.00043.x. PMID 26983654. S2CID 207598237.
29. Dietrich DE, Bode L, Spannhuth CW, Lau T, Huber TJ, Brodhun B, et al. (March 2000). "Amantadine in depressive patients with Borna disease virus (BDV) infection: an open trial". Bipolar Disorders. 2 (1): 65–70. 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. 27 (3). Elsevier BV: 191–201. doi:10.4103/0255-0857.53200. hdl:1807/53720. ISSN 0255-0857. PMID 19584498.

External links

• Viral diseases
• Neurological disorders
• Zoonoses
• Biology of bipolar disorder