(Ludwig & Bode, Intervirology (1997) 40:185-197)
| MicrobiologyBytes: Virology: Bornavirus | Updated: September 11, 2007 | Search |
MicrobiologyBytes: Latest Updates
Bornavirus, or Borna disease virus (BDV), infects a wide variety of vertebrates and belongs to the family Bornaviridae, part of the order Mononegavirales.
| Bornavirus particles are enveloped, spherical structures with a diameter
of 100-130 nm. They contain an crescent-like inner core structure with
a nucleocapsid approximately 4 nm in width, and an outer membrane envelope
with two kinds of glycoprotein spikes, GP43 and GP84. (Ludwig & Bode, Intervirology (1997) 40:185-197) |
|
Bornavirus particles contain one molecule of linear, negative-sense single stranded RNA around 8.9 kb long. Similarities of nucleotide sequence and ORF structure suggest that this family is closely related to the Rhabdoviridae. The genome of BDV contains at least six open reading frames (J Virol, 72: 783-788, 1998):
Entry:
Bornavirus enters the host cell via endocytosis. GP84 is thought to be involved in the attachment of to the cell surface receptor whereas GP43 is involved in the pH-dependent fusion after internalization of the virion by endocytosis. After internalization, the virus is taken up by endosomes.
Genome Replication:
The unique feature of bornavirus is that it is the only known member of the order Mononegvirales which replicates in the nucleus of host cell. Both positive- and negative-sense virus RNAs can be found within the nucleus of infected cells, but they are differentially located:
Replication also includes post-transcriptional modification of subgenomic RNAs by RNA splicing, although specific details on replication and splicing mechanisms are still unknown.
BDV is a noncytolytic, neurotropic RNA virus and the causative agent of Borna disease, a severe (frequently fatal) neurological disease of horses and sheep, characterised by progressive, nonpurulent encephalomyelitis. Borna disease was first described in a German veterinary handbook in 1766. It was characterized as a sporadic encephalopathy of horses and was later given the name "sad horse disease." In the late 1800’s an outbreak of this mysterious disease in the town of Borna in Saxony, Germany led to the death of almost all the horses of a cavalry regiment. The name Borna disease was subsequently adopted. In 1926 the cause of Borna disease was identified as Borna disease virus (BDV). In the decades that followed, naturally occurring BDV infection was documented in a variety of warm-blooded animals such as sheep and cattle. |
The symptoms of Borna disease in horses and sheep include behavioural changes, hyperactivity and disturbances in gait during the early stages of infection, with ataxia and partial paralysis being observed during the terminal stages of the disease. However, most natural BDV infections in horses seem to be asymptomatic, since BDV-specific antibodies are frequently found in clinically healthy horses. The natural host range of BDV as well as its geographic distribution may have been underestimated, as natural infections, many asymptomatic, have been reported in birds, wild and domestic cats, dogs, horses, sheep and cattle from different regions of the world. Experimentally, BDV has also been shown to have a wide host range, encompassing birds to primates. At present, it is therefore believed that the host range of BDV most likely includes all warm-blooded animals. The natural reservoir for BDV is not known, but rodents have been proposed as potential reservoir hosts because experimental infection of neonatal rats results in virus persistence. However, there is no evidence of natural infection in rodents, so this theory remains speculative.
Borna
Disease Virus: Role in Neurbehavioral Disease
Ed. Kathryn Carbone.
An encyclopedic compilation of recent and important discoveries in Borna Disease
Virus. Includes chapters on history, molecular virology, laboratory diagnosis
of infection, epidemology and natural infection, and human infection. For virologists,
microbiologists, psychiatrists, and veterinarians.
(Amazon.co.UK)
In 1985 antibodies against BDV antigens were first demonstrated in the blood of human psychiatric patients, sparking a debate as to whether BDV is involved in the pathogenesis of some human neuropsychiatric disorders. Subsequent serological and molecular studies have provided inconsistent evidence of an association between BDV infection and neuropsychiatric disorders, and the involvement of BDV in human psychiatric disease is unclear.
Transmission:
The routes of BDV transmission have yet to be fully proved, but intranasal infection is thought to be an important route of natural BDV infection, as the olfactory bulbs of naturally infected horses show inflammation early in the course of infection. It has also been suggested that animals may become infected by contact with bodily secretions and excretions, as these have been found to contain BDV RNA. Detection of BDV RNA and protein in peripheral blood also indicate the possibility of blood-borne transmission.
Neuropathogenesis:
In the early stage of infection, after initial replication in the neurons located at the site of entry, BDV migrates intraaxonally towards the central nervous system (CNS). In the case of intranasal infection, BDV migrates through the olfactory nerve. Once in the CNS, BDV exhibits a preferential tropism for the limbic system, including the hippocampus. The limbic system is involved in the regulation of memory, behaviour and emotions and appears to play a significant role in the pathogenesis of a number of human psychiatric disorders. Later in infection, BDV diffuses centrifugally through peripheral nerves, probably using axonal transport, and infects cells associated with the peripheral nervous system including astrocytes, oligodendrocytes and Schwann cells. If virus delivery via the peripheral nerves is sustained, non-neural organs and tissues can become infected.
The clinical symptoms of Borna disease result from the immune response of the host. Experimental infection of rats causes an immune–mediated biphasic behavioural disease, with symptoms of excitability, hyperactivity, movement and posture disorders consistent with natural infections. The onset of symptoms in experimentally infected rats coincides with the appearance of an inflammatory reaction in the brain, which can cause neuronal degeneration. In naturally infected animals, the caudate nucleus, dentate gyrus and hippocampus are the brain structures which show the most severe inflammation.
Despite reports of BDV reactive antibodies and BDV RNA in human blood and brains and the isolation of infectious BDV particles from psychiatric patients, the theory that BDV is involved in human psychiatric disorders is controversial. Several studies have reported no evidence of a statistically significant association between BDV infection and psychiatric disorders. The possibility that human BDV infection is a zoonotic illness which can be transmitted to individuals occupationally exposed to domestic animals, such as farmers, has received attention in the press, who have suggested that BDV infection might be linked to rural suicide and depression. The theory that Borna disease is a zoonosis is controversial and a study investigating BDV infection in UK farmers found that although there was some evidence to suggest farmers are exposed to BDV, the presence of BDV infection markers was not associated with psychiatric illness.
How
Pathogenic Viruses Work
by Lauren Sompayrac.
"Some of the best writing and the most logical presentation ever... A
style
that is both clear and entertaining... Had I encountered this book
in high school or college I suspect I would have changed my major from technical
and business
realms to medicine and virology."
(Amazon.co.UK)
Therapy:
Both amantadine and ribavirin have been show to have anti-bornavirus activity. Amantadine (Symmetrel), a glutamate receptor antagonist, has been shown to have antiviral activity against BDV in cell culture experiments, but may also have direct psychiatric effects on patients. In one study, administration of amantadine to a patient with bipolar depression had antidepressant effects, which were accompanied by an apparent clearance of BDV infection markers from the blood. However, it has been proposed that amantadine does not actually inhibit the replication of BDV, rather it modulates neurotransmitter systems leading to antidepressant effects. Another study found the application of amantadine had antidepressant effects in chronically depressed patients, but these effects did not correlate with clearance of BDV infection markers.
Search MEDLINE for the latest publications on this topic
© MicrobiologyBytes 2005.