Borna disease
Encyclopedia
Borna disease is an infectious neurological syndrome of warm-blooded
animals, caused by Borna disease virus, which causes abnormal behaviour and fatality.
The causative agent of Borna disease, Borna disease virus (BDV) is a neurotropic virus
and is a member of the Bornaviridae family within the Mononegavirales
order. Avian bornaviruses, a group of related viruses, have recently been identified as the cause of Proventricular Dilatation Disease
, a disease of pet birds.
Although the Borna disease virus is mainly seen as the causative agent of borna disease in horse
s 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.
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
.
or nasal secretions. Following infection, individuals may develop Borna disease, or may remain subclinical, possibly acting as a carrier of the virus.
s, cattle, sheep, dog
s and fox
es. In 1995, the virus was isolated from cat
s suffering from a "staggering disease" in Sweden
. Since that time, the virus 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 rat
s 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 horse
s in Europe
, it has since been found to occur in a wide range of warm-blooded animals including bird
s, cattle
, cat
s and primate
s 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:
In 1990, Janice E. Clements
and colleagues reported in the journal Science
that antibodies to a protein encoded by the Borna virus 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 BDV antibodies. Subsequent studies have also presented evidence for an association between Borna and human psychiatric disorders. However, not all researchers consider the link between Borna virus and human psychiatric disease to be conclusively proven. A recent study found no Borna virus antibodies in 62 patients with the deficit form of schizophrenia.
Additional evidence for a role of Borna virus 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 Borna 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
.
Warm-blooded
The term warm-blooded is a colloquial term to describe animal species which have a relatively higher blood temperature, and maintain thermal homeostasis primarily through internal metabolic processes...
animals, caused by Borna disease virus, which causes abnormal behaviour and fatality.
The causative agent of Borna disease, Borna disease virus (BDV) is a neurotropic virus
Virus
A virus is a small infectious agent that can replicate only inside the living cells of organisms. Viruses infect all types of organisms, from animals and plants to bacteria and archaea...
and is a member of the Bornaviridae family within the Mononegavirales
Mononegavirales
The order Mononegavirales is the taxonomic home of numerous related viruses. Members of the order that are commonly known are, for instance, Ebola virus, human respiratory syncytial virus, measles virus, mumps virus, Nipah virus, and rabies virus. All of these viruses cause significant disease in...
order. Avian bornaviruses, a group of related viruses, have recently been identified as the cause of Proventricular Dilatation Disease
Proventricular Dilatation Disease
Proventricular Dilatation Disease is a disease affecting psittacines . It was first recognized and described in 1978 by Dr. Hannis L. Stoddard...
, a disease of pet birds.
Although the Borna disease virus is mainly seen as the causative agent of borna disease in horse
Horse
The horse is one of two extant subspecies of Equus ferus, or the wild horse. It is a single-hooved mammal belonging to the taxonomic family Equidae. The horse has evolved over the past 45 to 55 million years from a small multi-toed creature into the large, single-toed animal of today...
s and other animals, recent findings have implicated that borna virus may play a role in some human neurological and psychiatric conditions including bipolar disorder
Bipolar disorder
Bipolar disorder or bipolar affective disorder, historically known as manic–depressive disorder, is a psychiatric diagnosis that describes a category of mood disorders defined by the presence of one or more episodes of abnormally elevated energy levels, cognition, and mood with or without one or...
and depression.
BDV also infects humans and is therefore considered to be a zoonotic
Zoonosis
A zoonosis or zoonoseis any infectious disease that can be transmitted from non-human animals to humans or from humans to non-human animals . In a study of 1415 pathogens known to affect humans, 61% were 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
Bipolar disorder
Bipolar disorder or bipolar affective disorder, historically known as manic–depressive disorder, is a psychiatric diagnosis that describes a category of mood disorders defined by the presence of one or more episodes of abnormally elevated energy levels, cognition, and mood with or without one or...
.
Vectors
The mode of transmission of BDV is unclear but probably occurs through intranasal exposure to contaminated salivaSaliva
Saliva , referred to in various contexts as spit, spittle, drivel, drool, or slobber, is the watery substance produced in the mouths of humans and most other animals. Saliva is a component of oral fluid. In mammals, saliva is produced in and secreted from the three pairs of major salivary glands,...
or nasal secretions. Following infection, individuals may develop Borna disease, or may remain subclinical, possibly acting as a carrier of the virus.
Animals
Borna virus appears to have a wide host range, having been detected in horseHorse
The horse is one of two extant subspecies of Equus ferus, or the wild horse. It is a single-hooved mammal belonging to the taxonomic family Equidae. The horse has evolved over the past 45 to 55 million years from a small multi-toed creature into the large, single-toed animal of today...
s, cattle, sheep, dog
Dog
The domestic dog is a domesticated form of the gray wolf, a member of the Canidae family of the order Carnivora. The term is used for both feral and pet varieties. The dog may have been the first animal to be domesticated, and has been the most widely kept working, hunting, and companion animal in...
s and fox
Fox
Fox is a common name for many species of omnivorous mammals belonging to the Canidae family. Foxes are small to medium-sized canids , characterized by possessing a long narrow snout, and a bushy tail .Members of about 37 species are referred to as foxes, of which only 12 species actually belong to...
es. In 1995, the virus was isolated from cat
Cat
The cat , also known as the domestic cat or housecat to distinguish it from other felids and felines, is a small, usually furry, domesticated, carnivorous mammal that is valued by humans for its companionship and for its ability to hunt vermin and household pests...
s suffering from a "staggering disease" in Sweden
Sweden
Sweden , officially the Kingdom of Sweden , is a Nordic country on the Scandinavian Peninsula in Northern Europe. Sweden borders with Norway and Finland and is connected to Denmark by a bridge-tunnel across the Öresund....
. Since that time, the virus has also been detected in cats in Japan
Japan
Japan is an island nation in East Asia. Located in the Pacific Ocean, it lies to the east of the Sea of Japan, China, North Korea, South Korea and Russia, stretching from the Sea of Okhotsk in the north to the East China Sea and Taiwan in the south...
and Britain
United Kingdom
The United Kingdom of Great Britain and Northern IrelandIn the United Kingdom and Dependencies, other languages have been officially recognised as legitimate autochthonous languages under the European Charter for Regional or Minority Languages...
.
Borna virus has been detected in humans, and researchers have presented evidence connecting these infections with psychiatric
Psychiatry
Psychiatry is the medical specialty devoted to the study and treatment of mental disorders. These mental disorders include various affective, behavioural, cognitive and perceptual abnormalities...
disorders.
Experimental infection of rat
Rat
Rats are various medium-sized, long-tailed rodents of the superfamily Muroidea. "True rats" are members of the genus Rattus, the most important of which to humans are the black rat, Rattus rattus, and the brown rat, Rattus norvegicus...
s has been demonstrated to lead to learning impairments and altered social behaviour. The virus appears to be distributed primarily in the limbic system
Limbic system
The limbic system is a set of brain structures including the hippocampus, amygdala, anterior thalamic nuclei, septum, limbic cortex and fornix, which seemingly support a variety of functions including emotion, behavior, long term memory, and olfaction. The term "limbic" comes from the Latin...
of the brain, including the hippocampus
Hippocampus
The hippocampus is a major component of the brains of humans and other vertebrates. It belongs to the limbic system and plays important roles in the consolidation of information from short-term memory to long-term memory and spatial navigation. Humans and other mammals have two hippocampi, one in...
and entorhinal cortex
Entorhinal cortex
The entorhinal cortex is located in the medial temporal lobe and functions as a hub in a widespread network for memory and navigation. The EC is the main interface between the hippocampus and neocortex...
. These areas of the brain are considered to be of importance in emotion
Emotion
Emotion is a complex psychophysiological experience of an individual's state of mind as interacting with biochemical and environmental influences. In humans, emotion fundamentally involves "physiological arousal, expressive behaviors, and conscious experience." Emotion is associated with mood,...
.
Originally identified in sheep and horse
Horse
The horse is one of two extant subspecies of Equus ferus, or the wild horse. It is a single-hooved mammal belonging to the taxonomic family Equidae. The horse has evolved over the past 45 to 55 million years from a small multi-toed creature into the large, single-toed animal of today...
s in Europe
Europe
Europe is, by convention, one of the world's seven continents. Comprising the westernmost peninsula of Eurasia, Europe is generally 'divided' from Asia to its east by the watershed divides of the Ural and Caucasus Mountains, the Ural River, the Caspian and Black Seas, and the waterways connecting...
, it has since been found to occur in a wide range of warm-blooded animals including bird
Bird
Birds are feathered, winged, bipedal, endothermic , egg-laying, vertebrate animals. Around 10,000 living species and 188 families makes them the most speciose class of tetrapod vertebrates. They inhabit ecosystems across the globe, from the Arctic to the Antarctic. Extant birds range in size from...
s, cattle
Cattle
Cattle are the most common type of large domesticated ungulates. They are a prominent modern member of the subfamily Bovinae, are the most widespread species of the genus Bos, and are most commonly classified collectively as Bos primigenius...
, cat
Cat
The cat , also known as the domestic cat or housecat to distinguish it from other felids and felines, is a small, usually furry, domesticated, carnivorous mammal that is valued by humans for its companionship and for its ability to hunt vermin and household pests...
s and primate
Primate
A primate is a mammal of the order Primates , which contains prosimians and simians. Primates arose from ancestors that lived in the trees of tropical forests; many primate characteristics represent adaptations to life in this challenging three-dimensional environment...
s and has been found in animals in Europe, Asia
Asia
Asia is the world's largest and most populous continent, located primarily in the eastern and northern hemispheres. It covers 8.7% of the Earth's total surface area and with approximately 3.879 billion people, it hosts 60% of the world's current human population...
, Africa
Africa
Africa is the world's second largest and second most populous continent, after Asia. At about 30.2 million km² including adjacent islands, it covers 6% of the Earth's total surface area and 20.4% of the total land area...
and North America
North America
North America is a continent wholly within the Northern Hemisphere and almost wholly within the Western Hemisphere. It is also considered a northern subcontinent of the Americas...
. The name is derived from the town of Borna
Borna
Borna is a town in the Free State of Saxony, Germany, capital of the Leipzig district. It is situated approx. 30 km southeast of Leipzig. It has approx. 21,000 inhabitants.-History:Borna as a town is more than 750 years old....
in Saxony
Saxony
The Free State of Saxony is a landlocked state of Germany, contingent with Brandenburg, Saxony Anhalt, Thuringia, Bavaria, the Czech Republic and Poland. It is the tenth-largest German state in area, with of Germany's sixteen states....
, Germany
Germany
Germany , officially the Federal Republic of Germany , is a federal parliamentary republic in Europe. The country consists of 16 states while the capital and largest city is Berlin. Germany covers an area of 357,021 km2 and has a largely temperate seasonal climate...
, 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
Meningitis
Meningitis is inflammation of the protective membranes covering the brain and spinal cord, known collectively as the meninges. The inflammation may be caused by infection with viruses, bacteria, or other microorganisms, and less commonly by certain drugs...
and encephalomyelitis
Encephalomyelitis
Encephalomyelitis is a general term for inflammation of the brain and spinal cord, describing a number of disorders:* Acute disseminated encephalomyelitis or postinfectious encephalomyelitis, a demyelinating disease of the brain and spinal cord, possibly triggered by vaccination or viral...
. Clinical manifestations vary but may include excited or depressed behaviour, ataxia
Ataxia
Ataxia is a neurological sign and symptom that consists of gross lack of coordination of muscle movements. Ataxia is a non-specific clinical manifestation implying dysfunction of the parts of the nervous system that coordinate movement, such as the cerebellum...
, 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 ataxiaAtaxiaAtaxia is a neurological sign and symptom that consists of gross lack of coordination of muscle movements. Ataxia is a non-specific clinical manifestation implying dysfunction of the parts of the nervous system that coordinate movement, such as the cerebellum...
or excess movement)
History
The first antibodies to Borna virus 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 Borna virus, which indicate prior infection, and Borna virus antigen have also been detected in blood donors.Psychiatric disease
There is some evidence that there may be a relationship between Borna virus infection and psychiatric disease.In 1990, Janice E. Clements
Janice E. Clements
Janice Ellen Clements is Vice Dean for Faculty at the Johns Hopkins School of Medicine and the Mary Wallace Stanton Professor of Faculty Affairs. She is a professor in the departments of Molecular and Comparative Pathobiology, Neurology, and Pathology, and has a joint appointment in Molecular...
and colleagues reported in the journal Science
Science
Science is a systematic enterprise that builds and organizes knowledge in the form of testable explanations and predictions about the universe...
that antibodies to a protein encoded by the Borna virus 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 BDV antibodies. Subsequent studies have also presented evidence for an association between Borna and human psychiatric disorders. However, not all researchers consider the link between Borna virus and human psychiatric disease to be conclusively proven. A recent study found no Borna virus antibodies in 62 patients with the deficit form of schizophrenia.
Additional evidence for a role of Borna virus in psychiatric disorders comes from reports that the drug amantadine
Amantadine
Amantadine is the organic compound known formally as 1-adamantylamine or 1-aminoadamantane. The molecule consists of adamantane backbone that has an amino group substituted at one of the four methyne positions. This pharmaceutical is sold under the name Symmetrel for use both as an antiviral and an...
, which is used to treat influenza
Influenza
Influenza, commonly referred to as the flu, is an infectious disease caused by RNA viruses of the family Orthomyxoviridae , that affects birds and mammals...
infections, has had some success in treating depression and clearing Borna 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
Parkinson's disease
Parkinson's disease is a degenerative disorder of the central nervous system...
and may have direct effects on the nervous system
Nervous system
The nervous system is an organ system containing a network of specialized cells called neurons that coordinate the actions of an animal and transmit signals between different parts of its body. In most animals the nervous system consists of two parts, central and peripheral. The central nervous...
.