Bornaviridae: Borna Disease Virus

Updates on Bornaviridae

Borna-be-wild: Recent Findings
1. Brain potential amplitude varies as a function of Borna disease virus-specific immune complexes in obsessive-compulsive disorder.

A recent pilot study examined event related potentials in the brain of obsessive compulsive disorder patients and control subjects. The results imply a relationship between borna-disease virus activity (as represented by borna disease virus immune complexes) and attention deficits. This study suggests that the hyperactivity of brainwaves in the secondary visual areas and anterior cingulate gyrus are modulated by borna disease virus infection. The neurological mechanism for this association is thought to be a result of direct interactions of the borna disease virus with inhibitory neurotransmitters in the brain.
Dietrich, et al. "Brain potential amplitude varies as a function of Borna disease virus-specific immune complexes in obsessive-compulsive disorder." Molecular Psychiatry (2005) 10, 515.

2. What is the exact mechanism for Bornavirus replication?
    That is, how is bornavirus bornagain?

Genome trimming: A unique strategy for replication control employed by Borna disease virus.

Although the exact means of Bornavirus replication are still unknown, scientists are making great advances to uncover just how bornavirus replication produces bornavirus virions that are born-again and again and again. A recent article by Schneider et al. suggests that Borna disease virus uses a unique mechanism of genome trimming to control replication. The researchers suggest that this means of replication is what allows for noncytolytic virus persistence in neurons and astrocytes. This mechanism of active genome trimming at the 5' termini involves deletion of the viral genome, which limits viral gene expression. However, scientists propose that this replication mechanism is beneficial to the virus because it allows for persistence without inducing cytolytic effects.
Schneider, et al. "Genome trimming: A unique strategy for replication control employed by Borna disease virus." PNAS. March 1, 2005. Vol 102. No 9. 3441-3446.
Rosario, et al. "Functional Characterization of the Genomic Promoter of Borna Disease Virus (BDV): Implications of 3'-Terminal Sequence Heterogeneity for BDV Peristence." Journal of Virology, May 2005, p. 6544-6550, Vol 79, No. 10.

3. Born to Persist: Recent updates on Borna disease virus persistence
The negative regulator of Borna disease virus polymerase is a non-structural protein

Further research regarding the mechanisms by which borna disease virus successively persists in hosts provides evidence for negative regulation of viral polymerase by viral protein X. Schwardt, et al. suggest that viral protein X is only incorporated into viral particles in late infection, allowing for sufficient viral replication early in the course of infection. Schwardt et al.'s results suggest that X is a non-structural protein that is present in persistently infected cells and may allow for viral persistence through inhibitory interactions with the viral polymerase. Their conclusions were based on finding that viral protein X is absent from viral particles, but present in purified borna disease virus stock.
Schwardt, et al. "The negative regulator of Borna disease virus polymerase is a non-structural protein." J Gen Virol 86 (2005): 3163-3169.
Schneider, U. (2005). "Novel insights into the regulation of the viral polymerase complex of neurotropic Borna disease virus." Virus Res 111(2): 148-60.

4. Borna-pathology: Potential mechanisms for pathogenesis

The neuropathological mechanism for borna disease virus is the current topic of debate. A recent article involved examination of virion-infected neurons of the hippocampus in mice. Hans, et alÕs research provided more evidence for noncytolytic persistent infection of borna disease virus. Moreover, Hans et al. showed that borna disease virus infection blocked the BDNF-induced ERK 1/2 phosphorylation and disrupted BDNF-induced expression of synaptic vesicle proteins. Borna disease virus infection was thus shown to impair synaptogenesis and damage neuronal connectivity through hampering neurotrophin-regulated neuroplasticity. The results of Hans et al. suggest a possible mechanism for the association between borna disease virus infection and psychiatric syndromes.
Hans A, Bajramovic JJ, Syan S, Perret E, Dunia I, Brahic M, Gonzalez-Dunia D
Persistent, noncytolytic infection of neurons by Borna disease virus interferes with ERK 1/2 signaling and abrogates BDNF-induced synaptogenesis. FASEB J. 2004 May;18(7):863-5.

Does Borna Nurture Nature? "Neuron-glia interactions clarify genetic-environmental links in mental illness."
Further research on genetically engineered mice suggests a role for glial infected with borna disease virus in the neuropathogenesis of psychiatric disorders. However, this research is in mice., and its relevance to humans remains to be determined. 
Sawa A, Pletnikov MV, Kamiya A "Neuron-glia interactions clarify genetic-environmental links in mental illness." Trends Neurosci. 2004 Jun;27(6):294-7.

5. Borna-sanity: More evidence supporting a role for Borna disease virus in human behavioral disorders

For years, scientists have examined the potential role of borna disease virus infection in human neurological and psychiatric illnesses. However, the association between morbidity and borna disease virus seroprevalence remains a topic of debate.
A recent cross-sectional retrospective cohort experiment was conducted in UK farming communities to determine the epidemiological significance of Borna Disease virus. Through analyzing the seroprevalence of borna disease virus in farm communities (that contained borna disease virus infected horses and sheeps), Thomas et al. found that the seroprevalence of borna disease virus infection in these farm communities was not statistically significant in comparison with farm communities that did not have animals infected with borna disease virus. Furthermore, no significant correlation was found in these cohorts between borna disease virus seroprevalence and psychiatric illness.
However, although there is evidence that does not support a significant role for Borna Disease virus and human psychiatric disorders, a recent systemic review indicates that there is enough evidence that humans are exposed to the virus to substantiate further investigations on whether or not it plays a role in behavioral disorders. Chalmers, et al.Õs review found 75 papers published before Janurary 2000 regarding 44 different cases of the seroprevalence of borna disease virus in humans, of which five were case studies. Overall, they found that seroprevalence of the virus ranged from 0-48%, which is to broad a range for analysis using standard statistical methods. Chalmers et al concluded that further epidemiological research is necessary to determine the significance of borna disease virus in human populations.
Chalmers, R. M., D. R. Thomas, et al. (2005). "Borna disease virus and the evidence for human pathogenicity: a systematic review." Qjm 98(4): 255-74.

For more cutting-edge borna virus research:
Recent Research: The New-born on Borna