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neuron-glia interactions in the rat retina infected by borna disease virus.neuron-glia interactions in the borna disease virus (bdv)-infected rat retina were investigated with emphasis on the ultrastructural characterization of degenerative alterations in the ganglion cell and photoreceptor layer. immuno- and cytochemical techniques were applied to label microglia, macrophages and müller (macroglial) cells. four weeks after intracerebral infection of adult rats, the total thickness of the retina was considerably diminished, primarily due to the loss of photoreceptor se ...200010664411
regional cytokine, cytokine receptor and neuropeptide mrna changes associated with behavioral and neuroanatomical abnormalities in persistent, noninflammatory virus infection of neonatal rats. 199910668451
distribution of borna disease virus in the brain of rats infected with an obesity-inducing virus strain.experimental infection of lewis rats with borna disease virus (bdv), a nonsegmented, single-stranded rna virus, usually causes an immune-mediated biphasic neurobehavioral disorder. such animals develop a persistent infection of the cns with viral antigen expression in all brain regions and a disseminated nonpurulent meningoencephalitis. interestingly, intracerebral infection of lewis rats with a bdv-variant (bdv-ob) causes a rapid increase of body weight with the development of an obesity syndro ...200010668894
effects of neonatal rat borna disease virus (bdv) infection on the postnatal development of the brain monoaminergic systems.effects of neonatal borna disease virus infection (bdv) on the postnatal development of brain monoaminergic systems in rats were studied. tissue content of norepinephrine (ne), dopamine (da) and its metabolite, 3,4-dihydroxyphenol acetic acid (dopac), and serotonin (5-ht) and its metabolite, 5-hydroxyindole-3-acetic acid (5-hiaa) were assayed by means of hplc-ec in frontal cortex, cerebellum, hippocampus, hypothalamus and striatum of neonatally bdv-infected and sham-inoculated male lewis rats of ...200010675767
bornavirus isolates of human origin. 200010697008
characterization of the p protein-binding domain on the 10-kilodalton protein of borna disease virus.the borna disease virus (bdv) is the prototype member of the bornaviridae, and it replicates in the cell nucleus. the bdv p24p and p40n proteins carry nuclear localization signals (nls) and are found in the nuclei of infected cells. the bdv p10 protein does not have an nls, but it binds with p and/or n and is translocated to the nucleus. hence, p10 may play a role in the replication of bdv in the cell nucleus. here, we show that the p-binding domain is located in the n terminus of p10 and that s ...200010708460
a short leucine-rich sequence in the borna disease virus p10 protein mediates association with the viral phospho- and nucleoproteins.borna disease virus (bdv) is unique among the non-segmented negative-strand rna viruses of animals and man because it transcribes and replicates its genome in the nucleus of the infected cell. it has recently been discovered that bdv expresses a gene product of 87 amino acids, the p10 protein, from an open reading frame that overlaps with the gene encoding the viral p24 phosphoprotein. in addition, the p10 protein has been localized to intranuclear bdv-specific clusters containing viral antigens ...200010725419
detection of borna disease virus in a pregnant mare and her fetus.a pregnant mare showing pyrexia, reduced appetite, ataxia and paresis was euthanized and examined for the presence of borna disease virus (bdv). her brain, showing multiple neuronal degeneration and necrosis with hemorrhage, and the histologically normal brain of the fetus were both positive for bdv rna. the bdv nucleotide sequences were identical in the mare and fetus in the second open reading frame (orf). this is the first report of the possible vertical transmission of bdv in a horse.200010727831
synaptic pathology in borna disease virus persistent infection.borna disease virus (bdv) infection of newborn rats leads to a persistent infection of the brain, which is associated with behavioral and neuroanatonomical abnormalities. these disorders occur in the absence of lymphoid cell infiltrates, and bdv-induced cell damage is restricted to defined brain areas. to investigate if damage to synaptic structures anteceded neuronal loss in bdv neonatally infected rats, we analyzed at different times postinfection the expression levels of growth-associated pro ...200010729116
bornagain? neurotrophic viruses in neuropsychiatry. 200010733289
expression and characterization of the borna disease virus polymerase.borna disease virus is the prototype of a new family, bornaviridae, within the order mononegavirales, that is characterized by nuclear transcription, splicing, low level replication, and neurotropism. the products of five open reading frames predicted from the genomic sequence have been confirmed; however, expression of the sixth, corresponding to the putative viral polymerase (l), has not been demonstrated. here, we describe expression and characterization of a 190-kda protein proposed to repre ...200010756058
microglial activation and neuronal apoptosis in bornavirus infected neonatal lewis rats.lewis rats neonatally infected with borna disease virus have a behavioral syndrome characterized by hyperactivity, movement disorders, and abnormal social interactions. virus is widely distributed in brain; however, neuropathology is focused in dentate gyrus, cerebellum, and neocortex where granule cells, purkinje cells and pyramidal cells are lost through apoptosis. although a transient immune response is present, its distribution does not correlate with sites of damage. neuropathology is inste ...200010764045
isolation of borna disease virus from human brain tissue.serological and molecular epidemiological studies indicate that borna disease virus (bdv) can infect humans and is possibly associated with certain neuropsychiatric disorders. we examined brain tissue collected at autopsy from four schizophrenic patients and two healthy controls for the presence of bdv markers in 12 different brain regions. bdv rna and antigen was detected in four brain regions of a bdv-seropositive schizophrenic patient (p2) with a very recent (2 years) onset of disease. bdv ma ...200010775596
[transmission of borna disease virus as etiopathogenetic factor in schizophrenia and affective disorders].borna disease virus (bdv) is a negative single-stranded ribonucleic acid (rna) virus, showing strong neurotropism. bdv may infect many different warm-blooded animal species, causing neurological and behavioral disorders. seroepidemiological studies suggest the existence of human infections with bdv and their higher prevalence in psychiatric patients. using different serological assays, anti-bdv antibodies were found in about 10%-20% of patients with schizophrenia, and in 1%-2% of the control gro ...199910776031
human bornaviruses and laboratory strains. 200010791549
human bornaviruses and laboratory strains. 200010791550
demonstration of borna disease virus nucleic acid in a patient with chronic fatigue syndrome. 200010823802
isolation and characterization of a new subtype of borna disease virus.borna disease virus (bdv), the causative agent of severe meningoencephalitis in a wide variety of animal species, has been considered to be genetically invariable and to form a single type within the genus bornavirus of the family bornaviridae. bdv infections are of particular interest, because for the first time a virus infection appears to be linked to human psychiatric disorders. we now describe a new subtype of bdv isolated from a horse which was euthanatized due to severe, incurable neurolo ...200010823873
no association of borna disease virus with psychiatric disorders among patients in northern kyushu, japan.there is controversy over the prevalence of borna disease virus (bdv) antibodies and its rna in the peripheral blood mononuclear cells (pbmcs) of psychiatric patients, and the contribution of bdv to human psychiatric disorders. we examined 299 plasma and 229 pbmc samples. no plasma samples were positive for bdv-p40, p24 or gp18 antibodies by western blot analysis. the prevalence of bdv rna in the psychiatric (schizophrenic) patients (1.8%) was not significantly different from that in the healthy ...200010861642
authentic borna disease virus transcripts are spliced less efficiently than cdna-derived viral rnas.borna disease virus (bdv) is a non-segmented, negative-strand rna virus that replicates and transcribes its genome in the nucleus of infected cells. it uses the cellular splicing machinery to generate a set of alternatively spliced mrnas from the 2.8 and 7.1 kb primary transcripts, each harbouring two introns. to determine whether splicing of these transcripts is regulated by viral factors, the extent of splicing was studied in infected cells and cos-7 cells transiently transfected with plasmids ...200010900032
a role for borna disease virus in schizophrenia? 200010904242
borna disease in a free-ranging lynx (lynx lynx).a free-ranging lynx (lynx lynx) was shot because of its abnormal behavior. histopathological examination revealed a nonsuppurative meningoencephalitis. in situ hybridization, immunohistochemistry, and reverse transcriptase pcr analysis showed the presence of borna disease virus infection in the brain. to our knowledge, this is the first confirmed case of borna disease in a large felid.200010921984
sequence variability of borna disease virus: resistance to superinfection may contribute to high genome stability in persistently infected cells.the rna genome of borna disease virus (bdv) shows extraordinary stability in persistently infected cell cultures. we performed bottleneck experiments in which virus populations from single infected cells were allowed to spread through cultures of uninfected cells and in which rnase protection assays were used to identify virus variants with mutations in a 535-nucleotide fragment of the m-g open reading frames. in one of the cell cultures, the major virus species (designated 2/1) was a variant wi ...200010933695
antibodies to borna disease virus in infected adult rats: an early appearance of anti-p10 antibody and recognition of novel virus-specific proteins in infected animal brain cells.the time course for appearance of antibodies to borna disease virus (bdv) major antigens, p40, p24, p18 and p10 were investigated in bdv-inoculated adult rats by western blotting. anti-p10 antibodies were detected in sera as early as anti-p40 and -p24 antibodies at four or five weeks after inoculation. furthermore, in addition to these major antigens of bdv, the rat serum could detect additional 80-, 58-, 43-, 20-, and 16-kda proteins in bdv-infected cultured cells and/or animal brain cells by w ...200010945300
epidemiology of borna disease virus. 200010950968
a rt-pcr assay for the rapid recognition of border disease virus.a reverse transcription--polymerase chain reaction (rt-pcr) method was developed for the specific detection of border disease virus (bdv), using the primers pbd1 and pbd2 flanking a 225 bp dna fragment, selected from the 5'noncoding region of the pestivirus genome. in tests on 70 pestiviruses it was shown to be bdv-specific. a closed, one-tube nested rt-pcr method employing general pestivirus outer primers (324 and 326), and the same bdv-specific inner primers (pbd1 and pbd2) in conjunction with ...200010958243
experimental and natural borna disease virus infections: presence of viral rna in cells of the peripheral blood.cells of the peripheral blood of experimentally and naturally borna disease virus (bdv)-infected animals and of human psychiatric patients and healthy individuals were analyzed for the presence of viral rna using a bdv-p40-specific nested reverse transcription-polymerase chain reaction (rt-pcr). the assay proved to be highly sensitive as 10 rna molecules were reproducibly amplified. bdv rna was detected in blood cells of experimentally infected immunocompetent mice and rats. mice were persistent ...200010973698
the mechanism of actinomycin d-mediated increase of borna disease virus (bdv) rna in cells persistently infected by bdv.the transcriptional mechanism of borna disease virus (bdv) has been poorly understood. we have analyzed transcription of the virus upon various stimuli in madin-darby canine kidney cells which were persistently infected by bdv (mdck/bdv). treatment with actinomycin d (actd) increased the level of bdv rna, shifting the size of rna from 1.9 kb to 2.3 kb beginning 5 hr after the treatment. to understand the mechanism of this unique modulation of bdv rna, we conducted several experiments. the rna in ...200010981833
chemokine gene expression in astrocytes of borna disease virus-infected rats and mice in the absence of inflammation.borna disease virus (bdv) causes cd8(+) t-cell-mediated meningoencephalitis in immunocompetent mice and rats, thus providing a valuable animal model for studying the mechanisms of virus-induced central nervous system (cns) immunopathology. chemokine-mediated leukocyte recruitment to the cns is a crucial step in the development of neurological disease. we found increased mrna levels of ip-10 and other chemokines in brains of adult rats following infection with bdv. the marked increase in chemokin ...200010982374
[detection of border disease virus in a sheep flock in saxony].a pestivirus has been isolated from brain samples of two lambs suffering from clinical signs of border disease. the two identical isolates were allocated to the "true" border disease virus group concerning their reaction pattern with monoclonal antibodies and the 5'utr sequence data. nevertheless, alterations of phenotype and genotype in comparison with references of both bdv-subgroups have been shown. the existence of an infection with border disease virus in the flock has been confirmed by ser ...200010994254
the genetic basis for cytopathogenicity of pestiviruses.two biotypes of pestiviruses, cytopathogenic (cp) and noncp viruses, can be distinguished by their effects on tissue culture cells. identification of cp bovine viral diarrhea virus (bvdv) has been frequently reported since antigenically closely related noncp and cp bvdv can be isolated from cattle with fatal mucosal disease (md) and are called a virus pair. in contrast to the bvdv system, only few cp border disease virus (bdv) and cp classical swine fever virus (csfv) strains have been described ...200011042405
phylogenetic, antigenic and clinical characterization of type 2 bvdv from north america.bovine viral diarrhea virus (bvdv) infection continues to have a significant impact upon us cattle producers despite the availability of more than 140 federally licensed vaccines. detection and control is hampered by viral heterogeneity that results in differences in neutralizing epitopes, cytopathology and virulence. recently it was found that there are two different genotypes, bvdv1 and bvdv2, among bvdv. bvdv2 isolates make up a significant proportion of the bvdv isolated in north america. se ...200011042408
borna disease virus persistence causes inhibition of glutamate uptake by feline primary cortical astrocytes.borna disease virus (bdv), a nonsegmented, negative-stranded (nns) rna virus, causes central nervous system (cns) disease in a broad range of vertebrate species, including felines. both viral and host factors contribute to very diverse clinical and pathological manifestations associated with bdv infection. bdv persistence in the cns can cause neurobehavioral and neurodevelopmental abnormalities in the absence of encephalitis. these bdv-induced cns disturbances are associated with altered cytokin ...200011044088
neurotrophic factor expression after cns viral injury produces enhanced sensitivity to psychostimulants: potential mechanism for addiction vulnerability.hypothesized risk factors for psychostimulant, amphetamine, and cocaine abuse include dopamine (da) receptor polymorphisms, hiv infection, schizophrenia, drug-induced paranoias, and movement disorders; however, the molecular, cellular, and biochemical mechanisms that predispose to drug sensitivity or drive the development of addiction are incompletely understood. using the borna disease rat, an animal model of viral-induced encephalopathy wherein sensitivity to the locomotor and stereotypic beha ...200011050146
identification of alternative splicing and negative splicing activity of a nonsegmented negative-strand rna virus, borna disease virus.borna disease virus (bdv) is a nonsegmented negative-strand rna virus that belongs to the mononegavirales. unlike other animal viruses of this order, bdv replicates and transcribes in the nucleus of infected cells. previous studies have shown that bdv uses rna splicing machinery for its mrna expression. in the present study, we identified spliced rnas that use an alternative 3' splice site, sa3, in bdv-infected cell lines as well as infected animal brain cells. transient transfection analysis of ...200011070091
borna disease virus persistent infection activates mitogen-activated protein kinase and blocks neuronal differentiation of pc12 cells.persistence of borna disease virus (bdv) in the central nervous system causes damage to specific neuronal populations. bdv is noncytopathic, and the mechanisms underlying neuronal pathology are not well understood. one hypothesis is that infection affects the response of neurons to factors that are crucial for their proliferation, differentiation, or survival. to test this hypothesis, we analyzed the response of pc12 cells persistently infected with bdv to the neurotrophin nerve growth factor (n ...200111073944
translation initiation of a bicistronic mrna of borna disease virus: a 16-kda phosphoprotein is initiated at an internal start codon.we examined translational initiation of a bicistronic 0.8-kb mrna of borna disease virus (bdv) using a cdna clone of the mrna. upon transfection with the clone, cos-7 cells produced a 16-kda protein (p'), in addition to the previously identified products of bdv, 24- (p) and 14.5-kda proteins. the 16-kda product was detected by anti-p monoclonal antibody and was shown to exist in bdv-infected cell lines as well as in infected animal brain cells. transient expression analysis of mutated cdna clone ...200011080477
deletions of structural glycoprotein e2 of classical swine fever virus strain alfort/187 resolve a linear epitope of monoclonal antibody wh303 and the minimal n-terminal domain essential for binding immunoglobulin g antibodies of a pig hyperimmune serum.the major structural glycoprotein e2 of classical swine fever virus (csfv) is responsible for eliciting neutralizing antibodies and conferring protective immunity. the current structural model of this protein predicts its surface-exposed region at the n terminus with a short stretch of the c-terminal residues spanning the membrane envelope. in this study, the n-terminal region of 221 amino acids (aa) covering aa 690 to 910 of the csfv strain alfort/187 e2, expressed as a fusion product in escher ...200011090160
molecular ratio between borna disease viral-p40 and -p24 proteins in infected cells determined by quantitative antigen capture elisa.we developed the antigen capture enzyme-linked immunosorbent assay (elisa) systems for quantification of borna disease virus (bdv) major antigens, p40 and p24. using these elisas, we quantified the two proteins in various bdv-infected materials, including the cell lysates and culture supernatants as well as the homogenates of experimental animal brains. the elisas were also applied to measure the infectious titer of bdv in persistently infected cell lines. quantitative analysis with these elisas ...200011092240
borna again, starting from the beginning. 200011126388
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 construc ...200011129800
search for borna disease virus in danish fibromyalgia patients.the purpose of this study was to look for borna disease virus (bdv) in 18 patients with acute onset of fibromyalgia (fms) following a "flu-like" episode. bdv is a neurotropic rna virus affecting horses and sheep. infections in animals have been reported to cause immune mediated disease characterized by abnormalities in behavior. a possible link between bdv and neuropsychiatric diseases in man has been described, and lately a connection to chronic fatigue syndrome (cfs) has been suggested.200011132208
neutralizing antibodies in persistent borna disease virus infection: prophylactic effect of gp94-specific monoclonal antibodies in preventing encephalitis.borna disease virus (bdv) infection triggers an immune-mediated encephalomyelitis and results in a persistent infection. the immune response in the acute phase of the disease is characterized by a cellular response in which cd8(+) t cells are responsible for the destruction of virus-infected brain cells. cd4(+) t cells function as helper cells and support the production of antiviral antibodies. antibodies generated in the acute phase of the disease against the nucleoprotein and the phosphoprotei ...200111134307
borna disease virus and schizophrenia in surinamese immigrants to the netherlands.borna disease virus (bdv) has been suggested to play a role in the etiology of schizophrenia. we tested the hypothesis that markers of bdv infection are more frequent in surinamese immigrants to the netherlands, diagnosed with schizophrenia, than in dutch-born healthy subjects. for reasons that are poorly understood there is an increased incidence of schizophrenia in this immigrant group. blood was obtained from 29 male schizophrenic patients (dsm-iv criteria) and from 26 healthy males. for dete ...200011138637
borna disease virus antibodies in french horses. 200011140933
the jury is still out on borna disease virus. 200111145825
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 ty ...200111145828
word recognition memory before and after successful treatment of depression.one of the most frequent and neuropsychologically well investigated symptoms in depression is reduced memory capacity. in this study, we investigated the course of disease in 16 patients with moderate depression and borna disease virus (bdv) infection. recently, it could be shown that bdv infection might play an important role in the etiology of subtypes of depression. amantadine treatment was used as an antidepressant and antiviral compound. in order to assess memory capacity, event-related pot ...200011147930
immunological and pcr analyses for borna disease virus in psychiatric patients and blood donors in japan.the involvement of borna disease virus (bdv) in psychiatric diseases in humans remains controversial. t-cell memory response and seroprevalence of bdv in patients with psychiatric disorders and blood donors in japan were evaluated collectively by western blot (wb) analysis with inhibition test, electrochemiluminescence immunoassay, immunofluorescence assay, and t-cell proliferative response as well as detection of bdv p24 rna in peripheral blood mononuclear cells (pbmcs). positive proliferative ...200111158085
borna disease virus-related therapy-resistant depression improved after cerebrospinal fluid filtration. 200011165306
identification and characterization of a new intron in borna disease virus.borna disease virus (bdv) has a non-segmented, negative-strand (nns) rna genome. in contrast to all other known nns rna animal viruses, bdv replication and transcription occur in the nucleus of infected cells. moreover, bdv uses rna splicing for the regulation of its genome expression. two introns (i and ii), both present in two viral primary transcripts of 2.5 and 7.2 kb, have been reported in bdv. here, evidence is provided of a new bdv intron, intron iii, generated by alternative 3' splice-si ...200111172106
neonatal borna disease virus infection (bdv)-induced damage to the cerebellum is associated with sensorimotor deficits in developing lewis rats.neonatal borna disease virus (bdv) infection of the brain produces developmental damage to the cerebellum in lewis rats, with minimal classical inflammatory responses. in the present study, we assessed the consequences of this damage by measuring motor coordination and postural skills in developing (postnatal days 4 to 30) lewis rats that were neonatally infected with bdv. neonatal bdv infection-induced motor impairments were selective and correlated with the time course of bdv damage to cerebel ...200111172881
alterations in neurotrophin and neurotrophin receptor gene expression patterns in the rat central nervous system following perinatal borna disease virus infection.infection of newborn rats with borna disease virus (bdv) leads to persistence in the absence of overt signs of inflammation. bdv persistence, however, causes cerebellar hypoplasia and hippocampal dentate gyrus neuronal cell loss, which are accompanied by diverse neurobehavioral abnormalities. neurotrophins and their receptors play important roles in the differentiation and survival of hippocampal and cerebellar neurons. we have examined whether bdv can cause alterations in the neurotrophin netwo ...200011175319
a separate disease within the syndrome of schizophrenia.if schizophrenia is a clinical syndrome rather than a single disease, the identification of specific diseases within the syndrome would facilitate the advance of knowledge and the development of more specific treatments. we propose that deficit psychopathology (ie, enduring, idiopathic negative symptoms) defines a group of patients with a disease different from schizophrenia without deficit features, as the deficit and nondeficit groups differ in their signs and symptoms, course, biological corr ...200111177118
learning deficits in mice with persistent borna disease virus infection of the cns associated with elevated chemokine expression.borna disease virus (bdv) is a highly neurotropic rna virus that causes a cd8(+) t cell-mediated neurological disease in certain mouse strains. we established asymptomatic persistent central nervous system (cns) infections in mutant c57bl/10j mice that lack functional cd8(+) t cells. when analyzed at adult age for spatial learning abilities in a water maze, bdv-infected mice showed slightly impaired escape performance while their exploratory behavior in an openfield test was indistinguishable fr ...200111182167
borna disease virus: new aspects on infection, disease, diagnosis and epidemiology.a 'disease of the head' affecting horses, as described in the 17th century is now known as borna disease. research over the past 100 years has established that the aetiological agent, borna disease virus (bdv), is an unsegmented, single- and negative-stranded, enveloped ribonucleic acid (rna) virus which represents the family bornaviridae in the order mononegavirales. the virus exists world-wide in horses, sheep, cattle, cats, dogs and ostriches. the infection can be fatal, but the majority of c ...200011189720
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 infe ...200011219351
borna disease virus nucleoprotein requires both nuclear localization and export activities for viral nucleocytoplasmic shuttling.nuclear transport of viral nucleic acids is crucial to the life cycle of many viruses. borna disease virus (bdv) belongs to the order mononegavirales and replicates its rna genome in the nucleus. previous studies have suggested that bdv nucleoprotein (n) and phosphoprotein (p) have important functions in the nuclear import of the viral ribonucleoprotein (rnp) complexes via their nuclear targeting activity. here, we showed that bdv n has cytoplasmic localization activity, which is mediated by a n ...200111238866
borna disease virus.borna disease virus (bdv) is unique amongst animal rna viruses in its molecular biology and capacity to cause persistent, noncytolytic cns-infection in a wide variety of host species. unlike other non-segmented negative-strand rna animal viruses, bdv replicates in the nucleus of the host cell where splicing is employed for expression of a very compact genome. epidemiological studies indicate a broad host range and geographical distribution, and some investigators have proposed that human infecti ...200111241801
borna disease virus and psychiatry.borna disease virus (bdv), a noncytolytic neurotropic nonsegmented negative-stranded rna virus with a wide geographic distribution, infects several vertebrate animal species and causes an immune-mediated central nervous system (cns) disease with various manifestations, depending on both host and viral factors. in animal infections, bdv can persist in the cns and induce alterations in brain cell functions, neurodevelopmental abnormalities and behavioral disturbances. an association between bdv an ...200111246286
amantadine in depressive patients with borna disease virus (bdv) infection: an open trial.originally introduced into pharmacotherapy as an antiviral compound, amantadine was shown to also have multiple pharmacological eftfects on the central nervous system. in addition. only a few studies reported on certain antidepressive properties of amantadine. this effect was highlighted by the discovery of its antiviral effect on borna disease virus (bdv), which is hypothesized to be an etiopathogenetic factor to subtypes of affective disorders. therefore, the therapeutical use of amantadine in ...200011254023
neurological diseases and viral dynamics in the brains of neonatally borna disease virus-infected gerbils.borna disease virus (bdv) is a noncytolytic, neurotropic rna virus that causes a chronic neurological disease in a wide variety of animal species. to develop a better understanding of the correlation between neurological disorders caused by bdv infection and virus distribution in the brain, we investigated viral dynamics in the central nervous system (cns) of neonatally bdv-infected gerbils during the late stage of infection. despite the severe symptoms and aggressive proliferation of bdv in the ...200111259191
a naturally processed rat major histocompatibility complex class i-associated viral peptide as target structure of borna disease virus-specific cd8+ t cells.the first naturally processed peptide synthesized by a virus and recognized by classical cd8(+) t cells in association with the rt1.a(l) major histocompatibility complex class i molecule of the lewis rat is reported. borna disease virus-specific cd8(+) t cells recognize syngeneic target cells pulsed with peptides extracted from borna disease virus-infected cells. the predicted peptide sequence asyaqmtty from the viral p40 protein coeluted with the cytotoxic t-lymphocyte-reactive fraction was ide ...200111278578
mek-specific inhibitor u0126 blocks spread of borna disease virus in cultured cells.borna disease virus (bdv) is a highly neurotropic virus that causes borna disease, a virus-induced immune-mediated encephalomyelitis, in a variety of warm-blooded animals. recent studies reported that bdv can be detected in patients with psychiatric disorders. bdv is noncytopathic, replicates in the nucleus of infected cells, and spreads intraaxonally in vivo. upon infection of susceptible cultured cells, virus can be detected in foci. little is known about the cellular components required for b ...200111312358
low avidity of human serum antibodies for borna disease virus antigens questions their diagnostic value.borna disease virus (bdv) can induce neurological disease in animals. since viral nucleic acid, infectious particles and antibodies recognizing bdv antigens were found at higher frequencies in psychiatric patients than in healthy controls, bdv is suspected to cause psychiatric disorders in humans. however, the human origin of these viruses has recently been questioned. to diagnose bdv infections, sera are usually analyzed for antiviral antibodies by indirect immunofluorescence (ifa) on virus-inf ...200111326304
electrophysiological properties of rat retinal müller (glial) cells in postnatally developing and in pathologically altered retinae.retinal glial müller cells are characterized by dominant k(+) conductances. the cells may undergo changes of their membrane currents during ontogeny and gliosis as described in rabbit and man. although the rat retina is often used in physiological experiments, the electrophysiology of rat müller cells is less well studied. the aim of the present study was to characterize their membrane currents in postnatal development and in two models of retinal degeneration. freshly isolated cells were subjec ...200111329181
genomic characterization of pestiviruses isolated from lambs and kids in southern italy.a nested polymerase chain reaction was used to identify 13 pestivirus strains isolated from small ruminants in several mixed (sheep and goats) flocks of southern italy, and for classification as bovine viral diarrhoea virus (bvdv) type 1, bvdv type 2, and border disease virus (bdv) genotypes. of the nine ovine isolates, two were characterized as bvdv type 1, and seven as bvdv type 2. the four pestiviruses isolated from kids belong to bvdv type 1. none of the pestivirus strains tested could be cl ...200111337042
seroprevalence of borna disease virus in domestic animals in xinjiang, china.to investigate the animals infected with borna disease virus (bdv) in xinjiang, china, we examined for bdv antibodies in the sera from groups of 20 horses, sheep and cattle, and from 165 wild rodents (18 species) by elisa and immunoblot. the serological study disclosed the presence of antibodies to both bdv-p24 and -p40 in the horses (20%) and sheep (25%), whereas no apparent positive reaction was detected either in cattle or rodents. the results suggested that bdv is prevalent in horses and she ...200111348775
borna disease virus-reactive antibodies and recent-onset psychiatric disorders. 200111353599
borna disease virus--does it infect humans and cause psychiatric disorders?antibodies recognizing borna disease virus (bdv) antigens were first demonstrated in the blood of psychiatric patients approximately 15 years ago. since that time, a highly controversial debate arose whether bdv infects humans and whether it causes psychiatric disorders. in this review, we critically discuss the results of numerous studies that assessed this possibility by using virological and serological methods. we conclude that there is presently no strong experimental evidence supporting th ...200111378492
interactions of viral proteins with neurotransmitter receptors may protect or destroy neurons. 200111417131
borna disease virus infection of adult and neonatal rats: models for neuropsychiatric disease.animal models provide unique opportunities to explore interactions between host and environment. two models have been established based on borna disease virus infection that provide new insights into mechanisms by which neurotropic agents and/or immune factors may impact developing or mature cns circuitry to effect complex disturbances in movement and behavior. note in press: since this chapter was submitted, several manuscripts have been published that extend findings reported here and support ...200111417134
[differential diagnosis of classical swine fever and border disease: seroepidemiological investigation of a pestivirus infection on a mixed sheep and swine farm].during recent years neutralizing antibodies against border disease virus (bdv) were found repeatedly in german pig herds. consequently there was a demand for a differential diagnostic system. a permanent sheep cell line and bdv reference strain moredun were chosen and were applied in a could be used case study. a pestivirus could be isolated from piglets on a mixed farm and was characterised as 'non-classical swine fever' (csf) by using monoclonal antibodies. due to a csf suspicion the pig herd ...200111417380
borna disease virus and human disease.the biology of borna disease virus (bdv) strongly supports the likelihood of human infection with bdv or a variant of bdv. thus far, the evidence supporting bdv infection in humans has initiated much controversy among basic and clinical scientists; only time and additional research will support or refute the hypothesis of human bdv infection. until an assay of acceptable specificity and sensitivity has been developed, validated, and used to document human bdv infection, scientists cannot reasona ...200111432811
borna disease virus and neuropsychiatric disease--a reappraisal.despite progress in understanding the molecular biology and pathobiology of borna disease virus, its epidemiology and role in human disease remain controversial. the challenges encountered in this field are a paradigm for the investigation of diseases potentially linked to complex host-microorganism interactions.200111435078
n-terminal domain of borna disease virus g (p56) protein is sufficient for virus receptor recognition and cell entry.borna disease virus (bdv) surface glycoprotein (gp) (p56) has a predicted molecular mass of 56 kda. due to extensive posttranslational glycosylation the protein migrates as a polypeptide of 84 kda (gp84). the processing of gp84 by the cellular protease furin generates gp43, which corresponds to the c-terminal part of gp84. both gp84 and gp43 have been implicated in viral entry involving receptor-mediated endocytosis and ph-dependent fusion. we have investigated the domains of bdv p56 involved in ...200111435588
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 ...200111443538
bornavirus and psychiatric disorders -- fact or fiction? 200111444766
bornavirus tropism and targeted pathogenesis: virus-host interactions in a neurodevelopmental model.animal models provide unique opportunities to explore interactions between host and environment. two models have been established based on bornavirus infection that provide new insights into mechanisms by which neurotropic agents and/or immune factors may impact developing or mature cns circuitry to effect complex disturbances in movement and behavior. distinct losses in da pathways in the adult infection model, and the associated dramatic movement disorder that accompanies it, make it an intrig ...200111450312
rat model of autism spectrum disorders. genetic background effects on borna disease virus-induced developmental brain damage. 200111462786
synthetic peptide-based electrochemiluminescence immunoassay for anti-borna disease virus p40 and p24 antibodies in rat and horse serum.borna disease virus (bdv) is a neurotropic pathogen that infects a wide variety of vertebrates. we have developed a new electrochemiluminescence immunoassay (eclia) for the detection of antibodies to bdv, using three synthetic peptides corresponding to the amino acid residues 3-20 and 338-358 of p40 and 59-79 of p24 peptide of bdv. using the eclia, we examined serum samples for the presence of anti-bdv antibodies in 20 rats (experimentally bdv-infected and uninfected) and 38 horses (13 us horses ...200111471876
alpha/beta interferon promotes transcription and inhibits replication of borna disease virus in persistently infected cells.borna disease virus (bdv) is a noncytolytic rna virus that can replicate in the central nervous system (cns) of mice. this study shows that bdv multiplication was efficiently blocked in transgenic mice that express mouse alpha-1 interferon (ifn-alpha1) in astrocytes. to investigate whether endogenous virus-induced ifn might similarly restrict bdv, we used ifnar(0/0) mice, which lack a functional alpha/beta ifn (ifn-alpha/beta) receptor. as would be expected if virus-induced ifn were important to ...200111483767
evidence for the presence of two novel pestivirus species.the genus pestivirus of the family flaviviridae comprises four species, namely bovine viral diarrhea virus-1 (bvdv-1), bvdv-2, border disease virus (bdv), and classical swine fever virus (csfv). comparative analyses of partial sequences have suggested that pestivirus isolates from giraffe (giraffe-1) and reindeer (reindeer-1) are distinct from the established species (becher et al., virology 262, 64--71, 1999). in this study, we report the complete genomic sequences of pestivirus strains giraffe ...200111485413
electrophysiological alterations and upregulation of atp receptors in retinal glial müller cells from rats infected with the borna disease virus.infection with the neurotropic borna disease virus (bdv) causes an immune-mediated neurological disease in a broad range of species. in addition to encephalitis, bdv-infected lewis rats develop a retinitis histologically characterized by the loss of most retinal neurons. by contrast, the dominating retinal macroglia, the müller cells, do not degenerate. it is known from several models of neurodegeneration that glial cells may survive but undergo significant alterations of their physiological par ...200111494412
borna disease: virus-induced neurobehavioral disease pathogenesis.studies of the pathogenesis of neurobehavioral diseases following borna disease virus infections have been increasing rapidly over the past ten years. recent major advances have included a report of vertical transmission of the virus in its natural host, the horse, and a report of isolation of a novel variant, no/98, in that same species. in rats infected neonatally with the borna disease virus that lack blood-borne inflammation in the brain, evidence of an "endogenous" brain inflammatory respon ...200111495813
identification of the immunodominant h-2k(k)-restricted cytotoxic t-cell epitope in the borna disease virus nucleoprotein.borna disease virus (bdv)-induced immunopathology in mice is most prominent in strains carrying the major histocompatibility complex h-2k allele and is mediated by cd8(+) t cells that are directed against the viral nucleoprotein p40. we now identified the highly conserved octamer peptide teleissi, located between amino acid residues 129 and 136 of bdv p40, as a potent h-2k(k)-restricted cytotoxic t-cell (ctl) epitope. when added to the culture medium of l929 target cells, teleissi conferred sens ...200111507203
borna disease virus phosphoprotein binds a neurite outgrowth factor, amphoterin/hmg-1.the borna disease virus (bdv) p24 phosphoprotein is an abundant protein in bdv-infected cultured cells and animal brains. therefore, there is a possibility that binding of the p24 protein to cellular factor(s) induces functional alterations of infected neural cells in the brain. to identify a cellular protein(s) that interacts with bdv p24 protein, we performed far-western blotting with extracts from various cell lines. using recombinant p24 protein as a probe, we detected a 30-kda protein in al ...200111507219
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 dee ...200111514730
experimental infection of mice with borna disease virus (bdv): replication and distribution of the virus after intracerebral infection.to develop an animal model resembling natural asymptomatic borna disease virus (bdv) infections, bdv he/80 rat brain homogenate was passaged four times in adult sjl/j mice. within 12 months of observation, mice did not develop overt signs of disease. nucleotide sequencing of the rat isolate and the mouse isolates at the fourth passage revealed no difference in the deduced amino acids. viral rna was found in brain, heart, kidney, lung, liver, and urinary bladder. infectious virus was isolated fro ...200111517401
borna disease virus infection in fiv-positive cats in germany. 200111517984
[the neuropathogenesis of borna disease virus infection].borna disease virus(bdv) is a noncytolytic, neurotropic rna virus that causes a disease of the central nervous system(cns) in several vertebrate species, including horses, sheep, cats and ostriches. epidemiological studies using peripheral blood or brain samples revealed that bdv can infect humans and that it may be related with certain neuropsychiatric disorders. the unique genetic and biological properties of bdv indicate that bdv develops a persistent infection in the cns. furthermore, a line ...200111519168
the central nervous system inflammatory response to neurotropic virus infection is peroxynitrite dependent.we have recently demonstrated that increased blood-cns barrier permeability and cns inflammation in a conventional mouse model of experimental allergic encephalomyelitis are dependent upon the production of peroxynitrite (onoo(-)), a product of the free radicals no* and superoxide (o2*(-)). to determine whether this is a reflection of the physiological contribution of onoo(-) to an immune response against a neurotropic pathogen, we have assessed the effects on adult rats acutely infected with bo ...200111544340
detection of anti-borna disease virus antibodies from cats in asian countries, japan, philippines and indonesia using electrochemiluminescence immunoassay.anti-borna disease virus (bdv) antibodies were detected from cats in japan, philippines and indonesia by using electrochemiluminescence immunoassay. positive rates were 3.1%, 3.8% and 2.0% in japan, philippines and indonesia, respectively. there was no differences in the positive rate of anti-bdv antibodies between male and female cats and among habitats. while, a significantly (p<0.05) higher prevalence (6.5%) was found in the oldest age group (more than 6 years) cats.200111558551
borna disease virus rna is absent in chronic multiple sclerosis. 200111558804
wild birds as a possible natural reservoir of borna disease virus.the natural reservoir of borna disease virus (bdv) is unknown. in this paper, we show that mallards (anas platyrhyncos) and jackdaws (corvus monedula) can be subclinically infected carriers of this virus. from faecal samples collected at a bird pond, we were able to amplify fragments of the bdv p24 and p40 genes. following cloning and sequencing, a phylogenetic analysis revealed that these birds carry strains of bdv closely related to but distinct from the reference strains bdv v and he/80. to o ...200111561971
cd8(+) t lymphocytes mediate borna disease virus-induced immunopathology independently of perforin.perforin-mediated lysis of target cells is the major antiviral effector mechanism of cd8(+) t lymphocytes. we have analyzed the role of perforin in a mouse model for cd8(+) t-cell-mediated central nervous system (cns) immunopathology induced by borna disease virus. when a defective perforin gene was introduced into the genetic background of the borna disease-susceptible mouse strain mrl, the resulting perforin-deficient mice developed strong neurological disease in response to infection indistin ...200111581414
infectobesity: obesity of infectious origin.in the u.s., the prevalence of obesity increased by 30% from 1980 to 1990, and this increase appears to be continuing. although obesity has multiple etiologies, an overlooked possibility is obesity of an infectious origin. six pathogens are reported to cause obesity in animals. canine distemper virus was the first virus reported to cause obesity in mice, followed by rous-associated virus-7, an avian retrovirus, which has been shown to cause stunting, obesity and hyperlipidemia in chickens. next, ...200111584109
conservation of coding potential and terminal sequences in four different isolates of borna disease virus.we determined the complete nucleotide sequences of two poorly characterized strains of borna disease virus (bdv) and compared them to reference strains v and he/80. strain h1766 was almost 98% and 95% identical to strains v and he/80, respectively, whereas strain no/98 was only about 81% identical to both reference strains. in contrast to earlier reports, we found an additional a residue at the extreme 3'-end of the single-stranded rna genome in all four bdv strains. the exact numbers of nucleot ...200111602780
an improved protocol for measuring cytotoxic t cell activity in anatomic compartments with low cell numbers.the study of target cell lysis and cytokine production are valuable tools to characterize antigen-specific t and nk cell function during virus infections. after localized infections in compartments such as the lung or the brain, however, cell numbers isolated from these organs are too low to perform standard assays with individual mice. here, we report a few simple modifications of the classical 51cr release assay allowing reduction of the number of required effector cells by a factor of 10 with ...200111687249
high-dose borna disease virus infection induces a nucleoprotein-specific cytotoxic t-lymphocyte response and prevention of immunopathology.experimental borna disease virus (bdv) infection of rats and natural infection of horses and sheep leads to severe central nervous system disease based on immunopathological pathways. the virus replicates slowly, and the cellular immune response results in immunopathology. cd8(+) t cells exert effector cell functions, and their activity results in the destruction of virus-infected cells. previously, oldach and colleagues (d. oldach, m. c. zink, j. m. pyper, s. herzog, r. rott, o. narayan, and j. ...200111689651
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