Borna disease

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style="background:#Template:Taxobox colour;"|Borna disease virus
style="background:#Template:Taxobox colour;" | Virus classification
Group: Group V ((-)ssRNA)
Order: Mononegavirales
Family: Bornaviridae
Genus: Bornavirus
Type species
Borna disease virus

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

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Overview

Borna disease is an infectious neurological syndrome of warm-blooded animals, which causes abnormal behavior and fatality. Originally identified in sheep and horses in Europe, it has since been found to occur in a wide range of warm-blooded animals including birds, cattle, cats and primates and has been found in animals in Europe, Asia, Africa and North America. The name is derived from the town of Borna in Saxony, Germany, which suffered an epidemic of the disease in horses in 1885.

Borna disease in sheep and horses arises 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, ocular disorders and abnormal posture and movement. Mortality rates are 80-100% in horses and greater than 50% in sheep.

Borna disease in the horse gives rise to signs like:

  • Unusual posture, gait and ear positions
  • Movement Disturbances (principally ataxia or excess movement)
  • "Pipe smoking" - hay or straw in mouth, but no chewing

Borna Virus

The causative agent of Borna disease, Borna disease virus (BDV) is a neurotropic virus and is the sole member of the Bornaviridae family within the Mononegavirales order. It has the smallest genome (8.9 kilobases) of any Mononegavirales species and is unique within that order in its ability to replicate within the host cell nucleus.

Although the virus is mainly seen as the causative agent of borna disease in horses and other animals, recent findings have implicated that borna virus may play a role in some human neurological and psychiatric conditions including bipolar disorder and depression.

The mode of transmission of BDV 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.

BDV also infects humans and is therefore considered to be a zoonotic agent. The role of BDV in human illness is controversial and it is yet to be established whether BDV causes any overt disease in humans. However, correlative evidence exists linking BDV infection with neuropsychiatric disorders such as bipolar disorder.

Borna virus was isolated from a diseased horse in the 1970s, but the virus particles were difficult to characterise. Nonetheless, the virus' genome has been characterised. It is a linear negative-sense single stranded RNA virus in the order of the mononegavirales. This order contains the family of lyssaviruses which includes the viruses responsible for rabies. A new family named the bornaviridae was created to hold this virus.

Bornavirus Replication

Bornaviruses enter the host by endocytosis. After this virus has entered its host it is taken up by endosomes. Replication of the bornavirus occurs inside the nucleus. This is the only virus within the order Mononegavirales to do this. Bornaviruses have negative sense RNA genomes. The negative sense RNA is copied to make a positive sense RNA template. This template is then used to synthesise many copies of the negative sense RNA genome. This is like making copies of a mold, and then using these molds to make many many more viruses.

Borna Virus as an Agent of Human Disease

The first antibodies to Borna virus in humans were discovered in the mid-1980's. Since then, there have been conflicting results from various studies in regards to whether an association exists between the agent and clinical disease. Antibodies to Borna virus, which indicate prior infection, and Borna virus antigen have also been detected in blood donors.

Some other evidence cited in favour of the idea that borna virus could be responsible for human psychiatric disease includes the fact that the drug Amantadine, which is used to treat influenza infections, has had some success in treating depression. Nonetheless, there are counter-claims that borna virus infections are not cleared by amantadine. The issue is further complicated by the fact that amantadine is also used in the treatment of Parkinson's Disease, so may have direct effects on the nervous system.

The link between borna virus and human psychiatric disease is not yet conclusively proven, and there is much controversy among researchers about the validity of claims made. A recent study [2] found no borna virus antibodies in 62 patients with the deficit form of schizophrenia. Interestingly, the majority of studies to date do lead to an association between the viral agent and human psychiatric disorders, however there exists a widely acknowledged bias in the sciences toward publishing "positive" rather than "negative" findings, i.e. studies that fail to confirm hypothetical relationships.

The interest group should be limited to the Iindex which does have Borna Disease Virus (BDV) and psychiatric disorders. BDV interferes with normal interneuronal communication.

In the early 90's america en japan investigated a 1000 people with psychiatric disorders for the antibodies of the borna virus in japan. The results whore what nobody expected there whore 768 manic depressive and schizoprenic people with antibodies of the borna virus positive in there blood, the 300 normal people who whore tested whore negative.

Currently they are researching the effect of the virus on persons with psychiatric disorders in the köch institute, and the same research may also be done in Belgium. [1] [2] [3]

Effects in Other Species

Borna virus appears to have a wide host range, having been detected in horses, cattle, sheep, dogs and foxes. In 1995, the virus was isolated from cats suffering from a "staggering disease" in Sweden. Since that time, the virus has also been detected in cats in Japan and Britain.

In Germany, Japan and the USA the virus has been detected in humans, and it has a controversial association with human disease, particularly of the psychiatric kind.

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.

References

  1. Bode, L. and Ludwig, H. (2003) 'Borna Disease Virus Infection, a Human Mental-Health Risk. Clinical Microbiology Reviews. 16 (3): 534-545.
  2. http://cmr.asm.org/cgi/content/full/16/3/534?view=long&pmid=12857781
  3. Koprowski, H. and Lipkin, W. I. (Eds) (1995). Borna disease. Springer-Verlag.


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