Borna Disease

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), both of which are members of the species Mammalian 1 orthobornavirus. BoDV-1 and 2 cause abnormal behaviour and fatality. Borna disease viruses 1 and 2 are neurotropic viruses and members of the Bornaviridae family within the Mononegavirales order.

Although Borna disease viruses 1 and 2 are mainly seen as the causative agent of Borna disease in horses and other animals, they are also controversially discussed as human infectious agents and therefore as potential zoonotic agents. The role of BoDV-1 and -2 in human illness is controversial and it is yet to be established whether BoDV-1 or -2 cause any overt disease in humans. However, correlative evidence exists linking BoDV-1/2 infection with neuropsychiatric disorders such as bipolar disorder.

Animals affected

Borna diseases viruses 1 and 2 appear to have wide host ranges, having been detected in horses, cattle, sheep, dogs and foxes. In 1995, BoDV-1 was isolated from cats suffering from a "staggering disease" in Sweden. Since that time, BoDV-1 has also been detected in cats in Japan and Britain.

Borna virus has been detected in humans, and researchers have presented evidence connecting these infections with psychiatric disorders.

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.

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 virus name is derived from the town of Borna in Saxony, Germany, which suffered an epidemic of the disease in horses in 1885.

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.

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)

Cause

Vectors

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.

History

The first antibodies to BoDV-1 in humans were discovered in the mid-1980s. 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 BoDV-1, which indicate prior infection, and BoDV-1 antigen have also been detected in blood donors.

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. Counter-claims state 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 and may have direct effects on the nervous system.