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]
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.[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]
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.[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.
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]
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.[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]
Encephalitis
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]
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]
^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.
PMID2244211.
^
abRott 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.
PMID2069502.
S2CID36530027.
^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.
PMID16324750.