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At least 19 recordsLinked to original sources
PubMed1997

Clinical similarities and close genetic relationship of human and animal Borna disease virus.

Borna disease virus (BDV) is the prototype genus of a new family, Bornaviridae, within the order Mononegavirales. BDV naturally infects animals and man. The symptomatology in animals ranges from subclinical infection to rare cases of encephalitis. Asymptomatic infection seemed more frequent than expected, based on antibody data from 100 healthy horses derived from different stables with a history of diseased cases (30-40% carriers). Likewise, phasic episodes of a neurobehavioral syndrome followed by recovery were much more common than fatal neurologic disease. They were paralleled by expression of BDV antigens (N-protein p40, P-protein p24) and RNA transcripts in peripheral blood mononuclear cells, indicating viral activation. Representative longitudinal studies showed that episodes of depressive illness in humans as well as apathetic phases in infected horses were accompanied by antigen expression and followed a similar clinical course. After recovery, BDV antigen disappeared. This temporal congruence, together with the recent isolation of infectious BDV from such patients, points to a contributory role of this virus in human affective disorders. Successful amelioration of BDV-induced neurobehavioral disease in horses with antidepressants applied in psychiatry, supported a common viral pathomechanism, involving reversible disturbances of the neurotransmitter network in the limbic system. Sequences of genetic material amplified from infected animal tissue and human PBMCs revealed a close interspecies relationship and high sequence conservation of the BDV genome. In human BDV isolates, however, single unique mutations were prominent in four genes. This finding supports the hypothesis that despite of high genomic conservation, species-specific genotypes may be definable, provided the sequences are derived from RNA of infectious virus.

Aged↗
PubMed2005

Detection of Borna disease virus p24 RNA in peripheral blood cells from Brazilian mood and psychotic disorder patients.

BACKGROUND: Borna disease virus (BDV) is a virus that naturally infects a broad range of warm-blooded animals. BDV is an enveloped virus, non-segmented, negative-stranded RNA genome and has an organization characteristic of a member of Bornaviridae in the order of Mononegavirale. In the present work we investigated the presence of BDV p24 RNA in peripheral blood cells from 30 psychiatric patients (19 with mood disorder and 11 with psychotic disorder) and 30 healthy volunteers as the control group. METHODS: All subjects were interviewed by structured diagnostic criteria categorized according to the DSM-IV, Axis I (SCID-V). The presence of BDV p24 RNA was investigated by nested reverse transcriptase PCR (RT-PCR) using specific primers to p24 from BDV. The specificity of the detection was analyzed by the sequencing of PCR products. RESULTS: The mean duration of illness in mood and psychotic patients with p24 RNA of BDV was 25 (+/-12.3) years and the median age was 43.77 (+/-15.2) years. There were no significant differences in gender and age among patients and control group, neither duration of illness among patients with mood and psychotic disorders in the presence or absence of p24 RNA of BDV. We found a frequency of 33.33% (10/30) of BDV-RNA on patient's group and 13.33% (4/30) on control group. The given sequences revealed identity with GenBank database sequence for BDV. CONCLUSION: The detection of a higher level of BDV-RNA in the peripheral blood cells of patients than on control group should help our understanding of the pathogenesis in the disease.

Adolescent↗
PubMed2006

Epidemiological pattern of classical Borna disease and regional genetic clustering of Borna disease viruses point towards the existence of to-date unknown endemic reservoir host populations.

Classical Borna disease (cBD), a non-purulent encephalitis of solipeds and sheep, is endemic in certain areas of central Europe. The etiologic agent is Borna disease virus (BDV), thus far the only member of the family Bornaviridae. Based on epidemiological patterns of cBD and recent phylogenetic findings this review hypothesizes the possible existence of yet unknown BDV reservoir host populations, and analyzes critically BDVs from outside endemic regions.

Animals↗
PubMed2005

Novel insights into the regulation of the viral polymerase complex of neurotropic Borna disease virus.

Borna disease virus (BDV) genetic information is encoded in a highly condensed non-segmented RNA genome of negative polarity. Replication and transcription of the genome occurs in the nucleus, enabling the virus to employ the cellular splicing machinery to process primary transcripts and to regulate expression of viral gene products. BDV establishes a non-cytolytic, persistent infection that in animals is mainly restricted to neurons of the central nervous system. Based on these unique properties, BDV represents the prototype member of the virus family Bornaviridae in the order Mononegavirales. Analysis of molecular aspects of BDV replication has long been hampered by the lack of a reverse genetics system. Only recently, artificial BDV minigenomes permitted the reconstitution of the viral polymerase complex, allowing finally the recovery of BDV from cDNA. As in other families of the Mononegavirales, the active polymerase complex of BDV is composed of the polymerase (L), the nucleoprotein (N) and the phosphoprotein (P). In addition, the viral X protein was identified as potent negative regulator of polymerase activity. Protein interaction studies combined with minireplicon assays suggested that P is a central regulatory element of BDV replication that directs the assembly of the polymerase complex. Most intriguingly, BDV obtained from cDNA with variable genomic termini suggests a novel strategy for viral replication-control. BDV seems to restrict its propagation efficacy by defined 5' terminal trimming of genomic and antigenomic RNA molecules. This review will summarize these novel findings and will discuss them in the context of BDV neurotropism and persistence.

Animals↗
PubMed2000

Borna disease in horses.

Borna disease is a sporadically occurring, progressive viral polioencephalomyelitis that primarily affects horses and sheep. The etiological agent, Borna disease virus (BDV), is an enveloped, single-stranded RNA virus that has been classified in the new virus family Bornaviridae within the order Mononegavirales. Serological evidence of BDV infection has been found in an increasing number of countries throughout the world. After an incubation period lasting a few weeks to several months, BDV infection can cause locomotor and sensory dysfunction followed by paralysis and death. Borna disease is the result of a virus-induced immunopathological reaction. BDV-specific antibodies and viral RNA have been found in humans with various psychiatric disorders.

Animals↗
PubMed2003

A system of protein target sequences for anti-RNA-viral chemotherapy by a vitamin B6-derived zinc-chelating trioxa-adamantane-triol.

The synthesis of the structurally unusual heterotricyclic compound 1-[3-hydroxy-5-(hydroxymethyl)-2-methyl-4-pyridinyl]-2,8,9-trioxaadamantane-3,5,7-triol (trivially named bananin, BN) from pyridoxylidenephloroglucinol and a theoretical prospect on possible biological activities of BN are presented in this report. Pyridoxylidenephloroglucinol is synthesized by Knoevenagel condensation of the vitamin B6 aldehyde pyridoxal with phloroglucinol. Pyridoxylidenephloroglucinol rearranges to light-yellow (4'RS)-1',4'-dihydrobananin by refluxing in 5M hydrochloric acid. Air oxidation subsequently forms BN in the heat which immediately yields orange-yellow (4'RS)-4'-chloro-1',4'-dihydrobananin by 1,4-addition of hydrogen chloride. This intermediate could be isolated but, interestingly, not a BN hydrochloride. Brown BN is finally achieved by base-catalyzed elimination of hydrogen chloride from (4'RS)-4'-chloro-1',4'-dihydrobananin. Regarding possible biological activities, it was demonstrated that BN acts as zinc (Zn2+) chelator. Therefore, a target of interest could be the human immunodeficiency virus type 1 (HIV-1) zinc finger HIV-1 RNA-binding nucleocapsid protein p7 (NCp7). Through suggested zinc ejection from HIV-1 genomic RNA psi-element-binding and HIV-1-RNA-duplex packaging NCp7 by BN, thus rendering NCp7 functionally obsolete, it is deduced that HIV-1 replication and effective infectious virion encapsidation could be inhibited by BN. Furthermore, theoretical and structural considerations propose that BN is converted into bananin 5'-monophosphate (BNP) by the cell type-ubiquitous human enzyme pyridoxal kinase (EC 2.7.1.35). Together with the putative antilentiviral retinoid vitamin A-vitamin B6 conjugate analogue B6RA (Kesel, A. J. Biochem. Biophys. Res. Comm. 2003, 300, 793), BNP is postulated to serve as effector in a system of protein target sequences RX(D/E) of RNA virus components. Human immunodeficiency Retroviridae (HIVs) could possibly be influenced by B6RA and BNP. In addition, candidate targets of B6RA and BNP could be adsorption, transcription and/or viral RNA replication of an interestingly wide RNA virus selection including Picornaviridae (poliovirus, human coxsackievirus, hepatitis A virus), Flaviviridae (yellow fever virus, Dengue virus, West Nile virus, Kunjin virus, St. Louis encephalitis virus, hepatitis C virus), Togaviridae (rubella virus), Coronaviridae (human coronavirus, human SARS-associated coronavirus), Rhabdoviridae (rabies virus), Paramyxoviridae (human parainfluenza virus, measles virus, human respiratory syncytial virus), Filoviridae (Marburg virus, Ebola virus), Bornaviridae (Borna disease virus), Bunyaviridae (Hantaan virus), Arenaviridae (Lassa virus), and Reoviridae (human rotavirus). The postulated scope of 'metabolically trapped' BNP might resemble the antiviral spectrum of the RNA-viral virustatic ribavirin.

Adamantane↗
PubMed2006

Reverse-genetic approaches to the study of Borna disease virus.

Borna disease virus (BDV) is an enveloped virus that has a non-segmented, negative-strand RNA genome with the characteristic organization of the mononegaviruses. However, based on its unique genetic and biological features, BDV is considered to be the prototypic member of a new mononegavirus family, the Bornaviridae. BDV causes central nervous system (CNS) disease in a wide variety of mammals. This article discusses the recently developed reverse-genetics systems for BDV, and the implications for the elucidation of the molecular mechanisms underlying BDV-host interactions, including the basis of BDV persistence in the CNS and its associated diseases.

Animals↗
PubMed2001

Borna disease virus-specific circulating immune complexes, antigenemia, and free antibodies--the key marker triplet determining infection and prevailing in severe mood disorders.

Borna disease virus (BDV), a unique genetically highly conserved RNA virus (Bornaviridae; Mononegavirales), preferentially targets neurons of limbic structures causing behavioral abnormalities in animals. Markers and virus in patients with affective disorders and schizophrenia have raised worldwide interest. A persistent infection was suggestive from follow-up studies, but inconstant detectability weakened a possible linkage.This study for the first time discloses that detection gaps are caused by BDV-specific circulating immune complexes (CIC), and their interplay with free antibodies and plasma antigens (p40/p24). Screening 3000 sera each from human and equine patients over the past 4 years by new enzyme immunoassays (EIAs) revealed that BDV-CICs indicate 10 times higher infection rates (up to 30% in controls, up to 100% in patients) than did previous serology. Persistence of high amounts of CICs and plasma antigens correlates with severity of depression. Even BDV RNA could be detected in plasma samples with strong antigenemia. Our discovery not only explains the course of persistent infection, but offers novel easy-to-use diagnostic tools by which new insights into BDV-related etiopathogenesis of disease and epidemiology are possible.

Adult↗
PubMedDate not supplied

Construction of an internal standard used in RT nested PCR for Borna Disease Virus RNA detection in biological samples.

The highly neurotropic Borna Disease Virus (BDV), which belongs to the Mononegavirales order--Bornaviridae family--is generally detected using the RT-nested-PCR. If false positive results (often caused by laboratory contaminations) can be avoided, some false negative results which are mostly due to inhibitory effects of some reaction components and/or to sample preparation errors, can occur. Thus, in order to control the RT-PCR sample, an RNA internal standard molecule named "mimic" was constructed with the same primer recognition sites as the viral nucleic acids, flanking a heterologous DNA fragment of distinct molecular weight. Because of their different sizes, the mimic and viral PCR products can be easily discriminated by agarose gel electrophoresis. The co-amplification of both BDV and mimic RNA was performed on infected cells and on biological tissues such as the brain and blood, commonly known to contain PCR inhibitor components. After mimic sensitivity studies were achieved (2.5 fg of "p40 RNA mimic" and 0.25 fg of "p24 RNA mimic"), the competitive amplification reaction between both BDV and mimic RNA was performed on these tissues. The results confirmed that nervous tissue has an inhibitory effect on RT-PCR, which supports the necessity of BDV detection by a higher sensitive method such as RT nested PCR. Moreover, these results confirmed the interest of an internal standard for BDV RNA detection in biological samples.

Base Sequence↗
PubMedDate not supplied

Borna disease: current knowledge and virus detection in France.

For over two centuries, Borna disease (BD) has been described as a sporadically occurring infectious meningoencephalomyelitis affecting horses and sheep in Central Europe. Over the last decade, the BD epidemiology has been discussed. Firstly, its geographical distribution seems larger than what was previously thought. Secondly, the disease can affect a large number of warm-blooded animal species, including humans. The aetiological agent is the Boma disease virus (BDV), an enveloped, nonsegmented negative-stranded RNA virus classified in the new virus family Bornaviridae (Mononegavirales order). It can induce severe clinical signs of encephalitis with striking behavioural disturbances and may cause death. BDV genome has recently been detected in France in the blood and brain of several animal species (horses, bovines, foxes).

Animals↗
PubMed2001

Borna disease virus: a mystery as an emerging zoonotic pathogen.

For Central European veterinarians, Borna disease (BD) has been known for a long time as a sporadically occurring, progressive viral polioencephalomyelitis predominantly affecting horses and sheep and-as discovered in the last decade-an increasing number of domestic and zoo animals. The aetiological agent, the Borna disease virus (BDV), a negative-sense, single-stranded RNA virus classified in the new virus family Bornaviridae within the order Mononegavirales, can induce severe clinical signs typically of a viral encephalitis with striking behavioural disturbances. After an incubation period lasting a few weeks to several months, BDV-infection causes locomotor and sensory dysfunctions followed by paralysis and death. Natural infections seem to be subclinical in most cases. BD received world-wide attention when it was reported that sera and/or cerebrospinal fluids from neuro-psychiatric patients can contain BDV-specific antibodies. Since infected animals produce BDV-specific antibodies only after virus replication, it was assumed that the broad spectrum of BDV-susceptible species also includes man. However, reports describing the presence of other BDV-markers, i.e. BDV-RNA or BDV-antigen, in peripheral blood leukocytes or brain tissue of neuro-psychiatric patients are highly controversial and, therefore, the role of BDV in human neuro-psychiatric disorders is questionable. (c) 2001 Harcourt Publishers Ltd.

Animals↗
PubMed1994

Genomic organization of Borna disease virus.

Borna disease virus is a neurotropic negative-strand RNA virus that infects a wide range of vertebrate hosts, causing disturbances in movement and behavior. We have cloned and sequenced the 8910-nucleotide viral genome by using RNA from Borna disease virus particles. The viral genome has complementary 3' and 5' termini and contains antisense information for five open reading frames. Homology to Filoviridae, Paramyxoviridae, and Rhabdoviridae is found in both cistronic and extracistronic regions. Northern analysis indicates that the virus transcribes mono- and polycistronic RNAs and uses termination/polyadenylylation signals reminiscent of those observed in other negative-strand RNA viruses. Borna disease virus is likely to represent a previously unrecognized genus, bornaviruses, or family, Bornaviridae, within the order Mononegavirales.

Amino Acid Sequence↗
PubMed2002

Bornavirus and the brain.

Borna disease virus (BDV) causes central nervous system (CNS) disease that is frequently manifested by behavioral abnormalities. BDV is a nonsegmented, negative, single-stranded RNA virus. On the basis of its unique genetic and biologic features, BDV is the prototypic member of a new virus family, Bornaviridae, within the order Mononegavirales. Therefore, the investigation of the molecular and cell biology of BDV may provide new insights about virus-cell interactions in the CNS. BDV is an important model system for the investigation of viral persistence in the CNS. Serologic and molecular epidemiologic studies suggest that BDV can infect humans. Despite controversy about potential association with human neuropsychiatric illnesses, BDV affords an intriguing model for the study of these illnesses. Neonatal BDV-infected rats display neurodevelopmental, physiologic, and neurobehavioral abnormalities that closely parallel some of the main features associated with several human mental disorders.

Animals↗
PubMed2001

Evidence of Borna disease virus genome detection in French domestic animals and in foxes (Vulpes vulpes).

Borna disease virus (BDV) is an enveloped, non-segmented negative-stranded RNA virus which belongs to the Bornaviridae family. BDV is an aetiological agent of encephalitis in horses, sheep and several other vertebrate species. In order to extend our knowledge about the presence of BDV in France, a study based on BDV RNA detection by RT-nested-PCR was done with 196 animal tissues: 171 brain samples collected from different animal species (75 horses, 59 foxes, 31 cattle, 4 dogs, 1 sheep, 1 roe deer) and 25 horse blood samples. An RNA internal standard molecule was constructed and was co-amplified with the test template. This study reports the first detection of BDV RNA in France in 10 brain samples collected from horses, foxes and cattle, and from 14 horse blood samples. Detection of the BDV genome in the brains of six red foxes is the first evidence of BDV infection in this species.

Animals↗
PubMed2003

A reverse genetics system for Borna disease virus.

Borna disease virus (BDV) is an enveloped virus. Its non-segmented, negative-stranded RNA genome has the coding capability for six main polypeptides and has an organization characteristic of members of the order Mononegavirales. However, based on its unique genetics and biological features, BDV is considered to be the prototypic member of a new virus family, Bornaviridae. Here, the establishment of a reverse genetics system for BDV is described. Intracellular synthesis of a BDV RNA analogue or minigenome (MG) from a plasmid was driven by RNA polymerase I. Co-transfection with plasmids expressing the BDV polymerase (L), nucleoprotein (N) and phosphoprotein (P) under the control of RNA polymerase II allowed for BDV MG replication and expression. This process depended on a delicate N:P ratio, whereas the L:P ratio was less critical. Two isoforms of N, Np40 and Np38, are present in BDV-infected cells but only Np40 was strictly required for virus polymerase activity. BDV p10 polypeptide encoded by the P gene exhibited a strong inhibitory effect on BDV MG expression.

Animals↗
PubMed2005

Identification of the Borna disease virus (BDV) proteins required for the formation of BDV-like particles.

Borna disease virus (BDV) is an enveloped virus with a non-segmented, negative-strand RNA genome that has an organization characteristic of Mononegavirales. However, based on its unique genetics and biological features BDV is considered to be the prototypic member of a new virus family, Bornaviridae. Here, the use of a reverse genetic approach to identify the viral proteins required for packaging of BDV RNA analogues (MG) into infectious virus-like particles (VLPs) was described. Plasmids encoding individual BDV proteins under the control of a RNA polymerase II promoter were co-transfected with a plasmid that allows for intracellular synthesis of a BDV MG mediated by the cellular RNA polymerase I. Clarified lysates from transfected cells were passaged onto fresh cells that were previously transfected with plasmids expressing the minimal BDV trans-acting factors L, N and P required for RNA synthesis mediated by the BDV polymerase. Reconstitution of BDV MG-specific packaging and passage of infectious VLP was monitored by expression of the chloramphenicol acetyl transferase reporter gene present in the BDV MG. BDV M and G, in addition to L, N and P, were sufficient for the passage of chloramphenicol acetyl transferase activity, which could be blocked by BDV neutralizing antibodies to G, indicating that VLP infectivity was fully mediated by BDV G. Passage of BDV MG was abrogated by omission of either M or G.

Borna disease virus↗
PubMed1997

The glycosylated matrix protein of Borna disease virus is a tetrameric membrane-bound viral component essential for infection.

Borna disease virus (BDV) is representative of the family of Bornaviridae in the order Mononegavirales (negative-stranded, non-segmented, enveloped RNA viruses). It is the causal agent for Borna disease, characterized as an encephalomyelitis (typical form) in a wide variety of domestic animals (from rodents to birds). Recent information shows the involvement of BDV in the pathogenesis of some human psychiatric disorders. The 8.9-kb viral antigenome codes for five major ORF. The third ORF codes for a 16-kDa protein (matrix protein) that is posttranslationally modified, yielding an N-linked glycoprotein. Our data show that the glycosylated matrix protein exists as a stable tetrameric structure detectable either by electrospray ionization or matrix-assisted laser-desorption ionization mass spectrometry. Under native conditions, the tetramer, with a relative molecular mass of 68 kDa, was isolated from a sediment-free brain suspension of a BDV-infected horse. The 68-kDa entity is stable in the presence of ionic and nonionic detergents but dissociates into subunits when heated. We found that the tetrameric matrix protein inhibits in vitro BDV infection in a dose-dependent manner. In contrast to inhibition of BDV infection with hydrophobic carbohydrate derivatives and protein-bound glycoconjugates, the glycosylated matrix protein is a very potent inhibitor of BDV infection, indicating that this protein represents an essential virus-specific membrane component for viral attachment.

Animals↗
PubMed1997

Borna disease virus (BDV), a (zoonotic?) worldwide pathogen. A review of the history of the disease and the virus infection with comprehensive bibliography.

A comprehensive history of Borna disease virus (BDV) and this infection, including the complete bibliography, is presented. Over the last 200 years, descriptions of this 'head disease' of horses ('Kopfkrankheit der Pferde') have been given. Considerable losses in the horse population (< 0.8%) led to intensive clinical and (neuro-)pathological investigations of this meningitis cerebrospinalis which occurs with faint behavioural changes, occasionally followed by severe neurological symptomatology and death. The broad experimental host range reflects infections in nature which include horses, sheep, cattle, cats, dogs, rodents, ostriches, and some zoo animals. BDV infections are associated with phylogentically old brain areas, and the retina. Occasionally, expression in the autonomic nervous system occurs, besides its neurotropism BDV can spread to peripheral organs, especially to epithelial tissues and peripheral blood mononuclear cells. Infections of humans that can be monitored by antibodies, antigens or nucleic acids in blood samples are prominent features of future interest. BDV, the prototype of the family Bornaviridae is an enveloped spherical virus carrying an 8.9 kb single-stranded, non-segmented RNA with negative polarity which replicates in the nucleus. These features together with its considerable genetic stability make this non-cytopathogenic virus an evolutionary 'old pathogen' in nature.

Animals↗