Bornaviridae: Borna Disease Virus

Viral Profile

The classic hosts of BDV are horses, sheep and other farm animals, but the virus has been identified in animals as diverse as marsupials (the opossum) to rhesus monkeys. Lack of efficient detection techniques and frequent sub clinical infection inhibit good epidemiological studies, but currently natural infection has been reported only in Central Europe, North America, New Zealand, Japan, Iran, and Israel. Borna disease shows seasonal prevalence, occurring most often in spring and early summer.
Natural transmission seems most likely to occur along the olfactory route. Experimental data show that the virus is found in the olfactory bulb early in infection and that this path is efficient for inoculation. It has also been hypothesized that transmission may occur through saliva, conjunctivial secretions, and direct exposure to contaminated food and water.  Minimal epidemiological date for transmission among horses and sheep suggests that these natural hosts may be infected from a different animal reservoir.  The virus may be spread horizontally by infectious rat urine, similar to Hantavirus and Lassa virus.
There has been little epidemiological research on human BDV infection, but it seems most probably that BDV is a zoonoses that cannot be transmited person-to-person.  This is supported by studies that show the human infection rate to be highest in regions of central Europe where BDV is endemic to animals, but without more evidence this remains uncertain.

BDV causes non-cytolitic, persistent infection of the central nervous system. Study of BDV pathology remains hindered by the lack of good ex vivo models of infection, but recent studies have made significant advances.
It seems that the virus may enter the CNS by neuroaxxonal migration along the olfactory nerve and spread by intraaxonal transport.  It replicates at low levels, producing small amounts of infectious particles that primarily spread directly cell-to-cell.  BDV shows significant tropism for the limbic system, but may infect elsewhere; it has in some cases been isolated form the salivary and mammary glands and nasal mucosa membrane.
Borna disease is the result of the cell-mediated immune response against the virus.  Immune compromised animals do not develop clinical symptoms of the disease despite production of infectious BDV particles in the CNS.  This could also explain the lack of disease symptoms associated with neonate infection, as the host immune system has not fully developed this early.  At this stage, however, BDV can interfere with synaptogenesis by interfering with synaptic vesicle protein expression, thus damaging neural connectivity and plasticity.


The incubation period in animals varies, but is general three to four weeks. Since definitive causative links between BDV infection and human disease remain unclear, the incubation period and course of infection in humans is unknown.


    Borna disease virus has presented in animals with a range of neurological consequences, from fatal Borna disease to subtle behavioral alterations; some animals often show no clinical manifestations. Advanced age and immunodeficiency increase the probability of severe illness. Early infection seems to persist in the central nervous system to cause developmental and behavioral abnormalities. Recurrent episodes in surviving animals are possible and are frequently associated with stress.
        In animals, acute Borna disease is associated with behavioral disturbances that progress to severe meningoencephalopathy and massive neuronal destruction.  Outcomes vary greatly across species, but in horses mortality rates are 80 to 100%. In neonates, BDV infection interferes with the developing neuronal networks and causes developmental and behavioral abnormalities. Symptoms include hyperactivity, cognitive defects, stunted growth, abnormal social behavior and chronic anxiety.
    The ties between human disease and BDV remain largely speculative, but many studies suggest ties to a variety of psychiatric disorders from depression to schizophrenia. As in animals, there is likely a range of consequences associated BDV infection. One study for example, found 600% higher seroprevelence of BDV in psychiatric patients than surgical patients ages 17 to 30 suggesting a role in early development of psychiatric disorders. This is supported by some case studies that show disease progression following BDV infection similar to that shown in animals, involving muscle weakness, paresis and depressive apathetic behavior.  Seroprelevence among controls, however, shows that as for animals there is likely significant occurrence of sub clinical infection.


The antiviral drug amantadine sulfate may be a potential treatment for BDV. It has been demonstrated in vitro to inhibit wild-type BDV replication and spread of infection.  Amantadine has recently been used to successfully improve clinical symptoms of depression in humans.
    Experimental vaccines for BDV have had mixed results.  The immunopathology of infection caused some vaccines to exacerbate disease, but recent evidence suggests the possibility of effective inoculation. One study has showed success in protectively vaccinating immune competent mice with a combination of parapox and vaccina virus vectors expressing the BDV nucucleoprotien. The pre-exposure vaccination required the non-cytolytic antiviral activity of the CD8+ T cells of the immune system.