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epidemiology and host spectrum of borna disease virus infections.borna disease virus (bdv) has gained lot of interest because of its zoonotic potential, ability to introduce cdna of its rna transcripts into host genomes, and ability to cause severe neurobehavioural diseases. classical borna disease is a progressive meningoencephalomyelitis in horses and sheep, known in central europe for centuries. according to current knowledge, bdv or a close relative also infects several other species, including humans at least occasionally, in central europe and elsewhere ...201323223618
serological evidence for infections with borna disease virus in turkey.distribution of borna disease virus (bdv) infection outside endemic areas has been studied in several countries. we examined serum samples for anti-bdv antibodies in purebred racing horses and other domestic animals in turkey. in total serum samples of 437 animals including 282 horses, 50 sheep, 25 goats, 50 cattle, and 30 cats were tested by indirect immunofluorescence assay (ifa). anti-bdv antibodies were detected in 4.9% of horses, 12% of sheep, 4% of goats, 14% of cattle and 6.6% of cats. no ...201223227761
evolutionarily conserved interaction between the phosphoproteins and x proteins of bornaviruses from different vertebrate species.bornavirus, a non-segmented, negative-strand rna viruses, is currently classified into several genetically distinct genotypes, such as borna disease virus (bdv) and avian bornaviruses (abvs). recent studies revealed that bornavirus genotypes show unique sequence variability in the putative 5' untranslated region (5' utr) of x/p mrna, a bicistronic mrna for the x protein and phosphoprotein (p). in this study, to understand the evolutionary relationship among the bornavirus genotypes, we investiga ...201223236446
birds and bornaviruses.in 2008, avian bornaviruses (abv) were identified as the cause of proventricular dilatation disease (pdd). pdd is a significant condition of captive parrots first identified in the late 1970s. abv infection has subsequently been shown to be widespread in wild waterfowl across the united states and canada where the virus infects 10-20% of some populations of ducks, geese and swans. in most cases birds appear to be healthy and unaffected by the presence of the virus; however, infection can also re ...201223253163
borna disease virus-induced neuronal degeneration dependent on host genetic background and prevented by soluble factors.infection of newborn rats with borne disease virus (bdv) results in selective degeneration of granule cell neurons of the dentate gyrus (dg). to study cellular countermechanisms that might prevent this pathology, we screened for rat strains resistant to this bdv-induced neuronal degeneration. to this end, we infected hippocampal slice cultures of different rat strains with bdv and analyzed for the preservation of the dg. whereas infected cultures of five rat strains, including lewis (lew) rats, ...201323319640
borna disease virus encoded phosphoprotein inhibits host innate immunity by regulating mir-155.it has been reported that the borna disease virus (bdv) encoded phosphoprotein (p protein) can inhibit the activity of traf family member-associated nf-kappab activator (tank)-binding kinase 1 (tbk-1), thus preventing the induction of type i interferon (ifn). however, the effects of microrna on the regulation of bdv infection and the host's immune response have not been characterized. mir-155 was predicted to be complementary to the bdv p mrna by rnahybrid software. here, we showed that mir-155 ...201323428672
unilateral cerebellar hypoplasia and mesencephalic malformation in a hanoverian foal.neurological cases, especially in foals, are rare in the daily practical work. the most common causes are traumata and infectious diseases of the central nervous system (cns). this case report provides further insights into the wide spectrum of possible neuropathological lesions by detailing a complex malformation with unilateral neurological signs that occurred later post natum. thus, clinicians should also be aware of malformations in case of respective neurological patients. a hanoverian foal ...201323608891
mavs-mediated host cell defense is inhibited by borna disease virus.viruses often have strategies for preventing host cell apoptosis, which antagonizes viral replication. borna disease virus (bdv) is a neurotropic rna virus that establishes a non-cytolytic persistent infection. although bdv suppresses type i interferon (ifn) through (tank)-binding kinase 1 (tbk-1) associated bdv p protein, it is still unclear how bdv can survive in the host cell and establish a persistent infection. recently, it has been recognized that mitochondria-mediated apoptosis through th ...201323702035
absence of a robust innate immune response in rat neurons facilitates persistent infection of borna disease virus in neuronal tissue.borna disease virus (bdv) persistently infects neurons of the central nervous system of various hosts, including rats. since type i ifn-mediated antiviral response efficiently blocks bdv replication in primary rat embryo fibroblasts, it has been speculated that bdv is not effectively sensed by the host innate immune system in the nervous system. to test this assumption, organotypical rat hippocampal slice cultures were infected with bdv for up to 4 weeks. this resulted in the secretion of ifn an ...201323793543
human but not laboratory borna disease virus inhibits proliferation and induces apoptosis in human oligodendrocytes in vitro.borna disease virus (bdv) is a neurotropic virus that produces neuropsychiatric dysfunction in a wide range of warm-blooded species. several studies have associated bdv with human psychiatric illness, but the findings remain controversial. although oligodendrocytes are a major glial component of brain white matter and play a pivotal role in neuronal cell function, bdv's effects on human oligodendrocytes have not been clarified. here, the effects of two bdv strains, hu-h1 (isolated from a bipolar ...201323805250
comprehensive analysis of endogenous bornavirus-like elements in eukaryote genomes.bornaviruses are the only animal rna viruses that establish a persistent infection in their host cell nucleus. studies of bornaviruses have provided unique information about viral replication strategies and virus-host interactions. although bornaviruses do not integrate into the host genome during their replication cycle, we and others have recently reported that there are dna sequences derived from the mrnas of ancient bornaviruses in the genomes of vertebrates, including humans, and these have ...201323938751
borna disease virus nucleoprotein inhibits type i interferon induction through the interferon regulatory factor 7 pathway.the expression of type i interferon (ifn) is one of the most potent innate defences against viral infection in higher vertebrates. borna disease virus (bdv) establishes persistent, noncytolytic infections in animals and in cultured cells. early studies have shown that the bdv phosphoprotein can inhibit the activation of type i ifn through the tbk1-irf3 pathway. the function of the bdv nucleoprotein in the inhibition of ifn activity is not yet clear. in this study, we demonstrated irf7 activation ...201323939047
nucleocytoplasmic shuttling of viral proteins in borna disease virus infection.nuclear import and export of viral rna and proteins are critical to the replication cycle of viruses that replicate in the nucleus. borna disease virus (bdv) is a nonsegmented, negative-strand rna virus that belongs to the order mononegavirales. bdv has several distinguishing features, one of the most striking being the site of its replication. bdv rna is transcribed and replicated in the nucleus, while most other negative-strand rna viruses replicate in the cytoplasm. therefore, the nucleocytop ...201323965528
prospects for cannabinoid therapies in viral encephalitis.cannabinoids are promising therapies to support neurogenesis and decelerate disease progression in neuroinflammatory and degenerative disorders. whether neuroprotective effects of cannabinoids are sustainable during persistent viral infection of the cns is not known. using a rodent model of chronic viral encephalitis based on borna disease (bd) virus, in which 1 week treatment with the general cannabinoid win 55,212-2 has been shown to be neuroprotective (solbrig et al., 2010), we examine longer ...201324021420
analysis of borna disease virus trafficking in live infected cells by using a virus encoding a tetracysteine-tagged p protein.borna disease virus (bdv) is a nonsegmented, negative-stranded rna virus characterized by noncytolytic persistent infection and replication in the nuclei of infected cells. to gain further insight on the intracellular trafficking of bdv components during infection, we sought to generate recombinant bdv (rbdv) encoding fluorescent fusion viral proteins. we successfully rescued a virus bearing a tetracysteine tag fused to bdv-p protein, which allowed assessment of the intracellular distribution an ...201324027309
an association of virus infection with type 2 diabetes and alzheimer's disease.diabetes mellitus type 2 is a metabolic disorder characterized by high blood glucose due to insulin deficiency or resistance. alzheimer's disease (ad) is a complex neurodegenerative disease leading to irreversible loss of neurons, intellectual abilities, memory and reasoning. the worldwide prevalence of diabetes and ad in elderly population is a major public health concern. interestingly, both health issues are unraveling the puzzling links. the clinico-pathological relationship between diabetes ...201424059298
[bornaviruses].bornaviridae is an enveloped animal virus carrying an 8.9 kb non-segmented, negative-strand rna genome. the genus bornavirus contains two members infecting vertebrates, borna disease virus (bdv) and avian bornavirus (abv), which could preferably infect the nervous systems. bdv causes classical borna disease, a progressive meningoencephalomyelitis, in horses and sheep, and abv is known to induce proventricular dilatation disease, a fatal disease characterized by a lymphocytic, plasmacytic inflamm ...201224153231
evidence for borna disease virus infection in neuropsychiatric patients in three western china provinces.borna disease virus (bdv) is a non-cytolytic, neurotropic rna virus that can infect a wide variety of vertebrate species from birds and primates to humans. several studies have been carried out to investigate whether bdv is associated with neuropsychiatric diseases. however, this association is still inconclusive. two panels of subjects consisting of 1,679 various neuropsychiatric patients and healthy people from three western china provinces were enrolled in this study. bdv p24 or p40 rna in pe ...201424170181
serological markers of bornavirus infection found in horses in iceland.in a stable of eight horses in northern iceland, six horses presented with clinical signs, such as ataxia and reduced appetite, leading to euthanasia of one severely affected horse. serological investigations revealed no evidence of active equine herpes virus type 1 infection, a common source of central nervous system disease in horses, nor equine arteritis virus and west nile virus. another neurotropic virus, borna disease virus, was therefore included in the differential diagnosis list.201324180621
bicolored white-toothed shrews as reservoir for borna disease virus, bavaria, germany. 201324274262
borna disease virus infection in cats.bornaviruses are known to cause neurological disorders in a number of animal species. avian bornavirus (abv) causes proventricular dilatation disease (pdd) in birds and borna disease virus (bdv) causes borna disease in horses and sheep. bdv also causes staggering disease in cats, characterised by ataxia, behavioural changes and loss of postural reactions. bdv-infection markers in cats have been reported throughout the world. this review summarizes the current knowledge of borna disease viruses i ...201424480411
landscape features and reservoir occurrence affecting the risk for equine infection with borna disease virus.borna disease (bd) is a severe endemic and fatal disorder caused by the neurotropic borna disease virus (bdv) which mainly occurs in horses and sheep. borna disease virus belongs to the order mononegavirales, which includes many reservoir-bound viruses with high zoonotic and pathogenic properties including the filoviruses and lyssaviruses. clinically manifest bd occurs in endemic areas of germany, switzerland, liechtenstein, and austria. a seasonal accumulation of cases in spring and summer, inc ...201324502713
evidence for natural borna disease virus infection in healthy domestic animals in three areas of western china.borna disease virus (bdv) is a non-cytolytic, neurotropic rna virus that can infect many vertebrate species, including humans. to date, bdv infection has been reported in a range of animal species across a broad global geographic distribution. however, a systematic epidemiological survey of bdv infection in domesticated animals in china has yet to be performed. in current study, bdv rna and antibodies in 2353 blood samples from apparently healthy animals of eight species (horse, donkey, dog, pig ...201424573218
proteomics reveal energy metabolism and mitogen-activated protein kinase signal transduction perturbation in human borna disease virus hu-h1-infected oligodendroglial cells.borna disease virus (bdv) is a neurotropic, non-cytolytic rna virus which replicates in the cell nucleus targeting mainly hippocampal neurons, but also astroglial and oligodendroglial cells in the brain. bdv is associated with a large spectrum of neuropsychiatric pathologies in animals. its relationship to human neuropsychiatric illness still remains controversial. we could recently demonstrate that human bdv strain hu-h1 promoted apoptosis and inhibited cell proliferation in a human oligodendro ...201424637096
meta-analysis of infectious agents and depression.depression is a debilitating psychiatric disorder and a growing global public health issue. however, the relationships between microbial infections and depression remains uncertain. a computerized literature search of medline, isi web of knowledge, psycinfo, and the cochrane library was conducted up to may 2013, and 6362 studies were initially identified for screening. case-control studies detected biomarker of microorganism were included. based on inclusion and exclusion criteria, 28 studies we ...201424681753
the bicolored white-toothed shrew crocidura leucodon (hermann 1780) is an indigenous host of mammalian borna disease virus.borna disease (bd) is a sporadic neurologic disease of horses and sheep caused by mammalian borna disease virus (bdv). its unique epidemiological features include: limited occurrence in certain endemic regions of central europe, yearly varying disease peaks, and a seasonal pattern with higher disease frequencies in spring and a disease nadir in autumn. it is most probably not directly transmitted between horses and sheep. all these features led to the assumption that an indigenous virus reservoi ...201424699636
[pathogenic significance and possible pathogenic mechanism of human endogenous viruses in development of schizophrenia].the association between psychogenic illness and human endogenous viruses (hevs), including human endogenous retrovirus and borna disease virus, remains unclear. as the component of human genome, hevs may become the joint of various pathogenic factors of schizophrenia (sz), such as heredity, environment, and immunity. in this review, we strive to uncover the clinical and laboratory evidence for the roles and possible pathogenic mechanism of hevs in the development of sz.201424772906
a study on borna disease virus infection in domestic cats in japan.borna disease virus (bdv) infection causes neurological disease in cats. here, we report bdv infection in 199 hospitalized domestic cats in the tokyo area. bdv infection was evaluated by detection of plasma antibodies against bdv-p24 or -p40. bdv-specific antibodies were detected in 54 cats (27.1%). interestingly, the percentage of seropositive cats was not significantly different among the three clinical groups, i.e., healthy (29.8%), neurologically asymptomatic disease (22.2%) and neurological ...201424805904
glutamate and lipid metabolic perturbation in the hippocampi of asymptomatic borna disease virus-infected horses.borna disease virus (bdv) is a neurotropic, enveloped, non-segmented, negative-stranded rna virus that infects a wide variety of vertebrate species from birds to humans across a broad global geographic distribution. animal symptomatology range from asymptomatic infection to behavioral abnormalities to acute meningoencephalitis. asymptomatic bdv infection has been shown to be more frequent than conventionally estimated. however, the molecular mechanism(s) underyling asymptomatic bdv infection rem ...201424956478
evolution of mammalian and avian bornaviruses.recently, avian bornavirus (abv) was identified to be a new member of the bornaviridae family consisting solely of the mammal-infecting borna disease virus (bdv). here, to gain more insights into the evolution of these bornaviruses, the time-stamped n gene sequences of bdv genotype 1 (bdv1) and abv were subjected to bayesian coalescent analyses. the nucleotide substitution rates and the divergence times were estimated. age calculations suggested that the first diversification event of the analyz ...201425046276
human borna disease virus infection impacts host proteome and histone lysine acetylation in human oligodendroglia cells.borna disease virus (bdv) replicates in the nucleus and establishes persistent infections in mammalian hosts. a human bdv strain was used to address the first time, how bdv infection impacts the proteome and histone lysine acetylation (kac) of human oligodendroglial (ol) cells, thus allowing a better understanding of infection-driven pathophysiology in vitro.201425086498
heat stress is a potent stimulus for enhancing rescue efficiency of recombinant borna disease virus.recently developed vector systems based on borna disease virus (bdv) hold promise as platforms for efficient and stable gene delivery to the central nervous system (cns). however, because it currently takes several weeks to rescue recombinant bdv (rbdv), an improved rescue procedure would enhance the utility of this system. heat stress reportedly enhances the rescue efficiency of other recombinant viruses. here, heat stress was demonstrated to increase the amount of bdv genome in persistently bd ...201425154584
inhibition of borna disease virus replication by an endogenous bornavirus-like element in the ground squirrel genome.animal genomes contain endogenous viral sequences, such as endogenous retroviruses and retrotransposons. recently, we and others discovered that nonretroviral viruses also have been endogenized in many vertebrate genomes. bornaviruses belong to the mononegavirales and have left endogenous fragments, called "endogenous bornavirus-like elements" (ebls), in the genomes of many mammals. the striking features of ebls are that they contain relatively long orfs which have high sequence homology to the ...201425157155
borna disease virus (bdv) infection in psychiatric patients and healthy controls in iran.borna disease virus (bdv) is an evolutionary old rna virus, which infects brain and blood cells of humans, their primate ancestors, and other mammals. human infection has been correlated to mood disorders and schizophrenia, but the impact of bdv on mental-health still remains controversial due to poor methodological and cross-national comparability.201425186971
a viral peptide that targets mitochondria protects against neuronal degeneration in models of parkinson's disease.mitochondrial dysfunction is a common feature of many neurodegenerative disorders, notably parkinson's disease. consequently, agents that protect mitochondria have strong therapeutic potential. here, we sought to divert the natural strategy used by borna disease virus (bdv) to replicate in neurons without causing cell death. we show that the bdv x protein has strong axoprotective properties, thereby protecting neurons from degeneration both in tissue culture and in an animal model of parkinson's ...201425333748
real-time qpcr identifies suitable reference genes for borna disease virus-infected rat cortical neurons.quantitative real-time reverse transcription polymerase chain reaction (rt-qpcr) is the most commonly-used technique to identify gene expression profiles. the selection of stably expressed reference genes is a prerequisite to properly evaluating gene expression. here, the suitability of commonly-used reference genes in normalizing rt-qpcr assays of mrna expression in cultured rat cortical neurons infected with borna disease virus (bdv) was assessed. the expressions of eight commonly-used referen ...201425431926
taxonomic reorganization of the family bornaviridae.knowledge of bornaviruses has expanded considerably during the last decade. a possible reservoir of mammalian borna disease virus has been identified, divergent bornaviruses have been detected in birds and reptiles, and endogenous bornavirus-like elements have been discovered in the genomes of vertebrates of several species. previous sequence comparisons and alignments have indicated that the members of the current family bornaviridae are phylogenetically diverse and are not adequately classifie ...201525449305
discrepancy in the diagnosis of avian borna disease virus infection of psittaciformes by protein analysis of feather calami and enzyme-linked immunosorbent assay of plasma antibodies.the present study compares diagnosis of avian borna disease virus (abv) infection of psittacine birds by western blot of bornaviral proteins in dried feather stems with the detection of anti-bornaviral protein antibodies to bornaviral proteins in plasma by enzyme-linked immunosorbent assay (elisa). the detection of abv proteins p40 and p24 in feather calami by western blotting was possible even after storage of the dried feathers for several years at ambient temperature. serological identificati ...201525701023
borna disease virus possesses an nf-ĸb inhibitory sequence in the nucleoprotein gene.borna disease virus (bdv) has a non-segmented, negative-stranded rna genome and causes persistent infection in many animal species. previous study has shown that the activation of the iκb kinase (ikk)/nf-κb pathway is reduced by bdv infection even in cells expressing constitutively active mutant ikk. this result suggests that bdv directly interferes with the ikk/nf-κb pathway. to elucidate the mechanism for the inhibition of nf-κb activation by bdv infection, we evaluated the cross-talk between ...201525733193
viral immune surveillance: toward a th17/th9 gate to the central nervous system.viral cellular immune surveillance is a dynamic and fluid system that is driven by finely regulated cellular processes including cytokines and other factors locally in the microenvironment and systemically throughout the body. it is questionable as to what extent the central nervous system (cns) is an immune-privileged organ protected by the blood-brain barrier (bbb). recent evidence suggests converging pathways through which viral infection, and its associated immune surveillance processes, may ...201525780281
borna disease virus phosphoprotein modulates epigenetic signaling in neurons to control viral replication.understanding the modalities of interaction of neurotropic viruses with their target cells represents a major challenge that may improve our knowledge of many human neurological disorders for which viral origin is suspected. borna disease virus (bdv) represents an ideal model to analyze the molecular mechanisms of viral persistence in neurons and its consequences for neuronal homeostasis. it is now established that bdv ensures its long-term maintenance in infected cells through a stable interact ...201525810554
health care professionals at risk of infection with borna disease virus - evidence from a large hospital in china (chongqing).human borna disease virus (bdv) infections have recently been reported in china. bdv causes cognitive and behavioural disturbances in animals. the impact on human mental disorders is subject to debate, but previous studies worldwide have found neuropsychiatric patients more frequently infected than healthy controls. a few isolates were recovered from severely depressed patients, but contagiousness of bdv strain remains unknown.201525888756
borna disease virus phosphoprotein impairs the developmental program controlling neurogenesis and reduces human gabaergic neurogenesis.it is well established that persistent viral infection may impair cellular function of specialized cells without overt damage. this concept, when applied to neurotropic viruses, may help to understand certain neurologic and neuropsychiatric diseases. borna disease virus (bdv) is an excellent example of a persistent virus that targets the brain, impairs neural functions without cell lysis, and ultimately results in neurobehavioral disturbances. recently, we have shown that bdv infects human neura ...201525923687
borna disease virus infection impacts micrornas associated with nervous system development, cell differentiation, proliferation and apoptosis in the hippocampi of neonatal rats.micrornas (mirnas) regulate gene expression by inhibiting transcription or translation and are involved in diverse biological processes, including development, cellular differentiation and tumor generation. mirna microarray technology is a high‑throughput global analysis tool for mirna expression profiling. here, the hippocampi of four borna disease virus (bdv)‑infected and four non‑infected control neonatal rats were selected for mirna microarray and bioinformatic analysis. reverse transcriptio ...201526004383
borna disease virus infection in cats: abcd guidelines on prevention and management.borna disease virus (bdv) has a broad host range, affecting primarily horses and sheep, but also cattle, ostriches, cats and dogs. in cats, bdv may cause a non-suppurative meningoencephalomyelitis ('staggering disease').201526101313
persistent human borna disease virus infection modifies the acetylome of human oligodendroglia cells towards higher energy and transporter levels.borna disease virus (bdv) is a neurotropic rna virus persistently infecting mammalian hosts including humans. lysine acetylation (kac) is a key protein post-translational modification (ptm). the unexpectedly broad regulatory scope of kac let us to profile the entire acetylome upon bdv infection.201526210075
gc-ms-based metabonomic profiling displayed differing effects of borna disease virus natural strain hu-h1 and laboratory strain v infection in rat cortical neurons.borna disease virus (bdv) persists in the central nervous systems of a wide variety of vertebrates and causes behavioral disorders. previous studies have revealed that metabolic perturbations are associated with bdv infection. however, the pathophysiological effects of different viral strains remain largely unknown. rat cortical neurons infected with human strain bdv hu-h1, laboratory bdv strain v, and non-infected control (con) cells were cultured in vitro. at day 12 post-infection, a gas chrom ...201526287181
shedding of infectious borna disease virus-1 in living bicolored white-toothed shrews.many rna viruses arise from animal reservoirs, namely bats, rodents and insectivores but mechanisms of virus maintenance and transmission still need to be addressed. the bicolored white-toothed shrew (crocidura leucodon) has recently been identified as reservoir of the neurotropic borna disease virus 1 (bodv-1).201526313904
parrot bornavirus-2 and -4 rna detected in wild bird samples in japan are phylogenetically adjacent to those found in pet birds in japan.bornaviruses (family bornaviridae) are non-segmented negative-strand rna viruses. avian bornaviruses (abvs), which are causative agents of proventricular dilatation disease, are a genetically diverse group with at least 15 genotypes, including parrot bornaviruses (pabvs) and aquatic bird bornavirus 1(abbv-1). borna disease virus 1(bodv-1), which infects mammals and causes neurological diseases, has also been reported to infect avian species, although the numbers of the cases have been markedly f ...201526315330
surface glycoprotein of borna disease virus mediates virus spread from cell to cell.borna disease virus (bdv) is a non-segmented negative-stranded rna virus that maintains a strictly neurotropic and persistent infection in affected end hosts. the primary target cells for bdv infection are brain cells, e.g. neurons and astrocytes. the exact mechanism of how infection is propagated between these cells and especially the role of the viral glycoprotein (gp) for cell-cell transmission, however, are still incompletely understood. here, we use different cell culture systems, including ...201626332529
x-linked rna-binding motif protein (rbmx) is required for the maintenance of borna disease virus nuclear viral factories.borna disease virus (bdv) is a non-segmented, negative-strand rna virus that establishes persistent infection in the nucleus. although bdv forms viral inclusion bodies, termed viral speckles of transcripts (vspots), which are associated with chromatin in the nucleus, the host factors involved in the maintenance of vspots remain largely unknown. in this study, we identified x-linked rna-binding motif protein (rbmx) as a nuclear factor interacting with bdv nucleoprotein. interestingly, knockdown o ...201526333388
expression and role of the tgf-β family in glial cells infected with borna disease virus.a previous study revealed that the expression of the borna disease virus (bdv)-encoding phosphoprotein in glial cells was sufficient to induce neurobehavioral abnormalities resembling borna disease. to evaluate the involvement of the tgf-β family in bdv-induced changes in cell responses by c6 glial cells, we examined the expression levels of the tgf-β family and effects of inhibiting the tgf-β family pathway in bdv-infected c6 (c6bv) cells. the expression of activin βa and bmp7 was markedly incr ...201626482505
a novel intranuclear rna vector system for long-term stem cell modification.genetically modified stem and progenitor cells have emerged as a promising regenerative platform in the treatment of genetic and degenerative disorders, highlighted by their successful therapeutic use in inherent immunodeficiencies. however, biosafety concerns over insertional mutagenesis resulting from integrating recombinant viral vectors have overshadowed the widespread clinical applications of genetically modified stem cells. here, we report an rna-based episomal vector system, amenable for ...201626632671
transolfactory neuroinvasion by viruses threatens the human brain.viral neuroinvasion via the olfactory system has been investigated in a variety of virus-animal models by scientists in many fields including virologists, pathologists, and neurologists. in humans, herpes simplex virus type 1 (hsv-1), human herpesvirus 6 (hhv-6), borna disease virus, rabies virus, and influenza a virus have been shown to take the olfactory route for neuroinvasion based on forensic and post-mortem specimens. this article briefly summarizes the anatomy, physiology, and immunology ...201526666182
[the borna disease virus phosphoprotein alters the development of human gabaergic neurons]. 201526672653
manipulation of the n-terminal sequence of the borna disease virus x protein improves its mitochondrial targeting and neuroprotective potential.to favor their replication, viruses express proteins that target diverse mammalian cellular pathways. due to the limited size of many viral genomes, such proteins are endowed with multiple functions, which require targeting to different subcellular compartments. one salient example is the x protein of borna disease virus, which is expressed both at the mitochondria and in the nucleus. moreover, we recently demonstrated that mitochondrial x protein is neuroprotective. in this study, we sought to ...201626700735
neuropathogenesis of persistent infection with borna disease virus.borna disease virus (bdv), belonging to the non-segmented, negative-stranded rna viruses, persistently infects the central nervous system of many mammals. neonatal bdv infection in rodent models induces neurodevelopmental disturbance without overt inflammatory responses, resulting in a wide range of neurobehavioral abnormalities, such as anxiety, abnormal play behaviors, and cognitive deficits, resembling those of autism patients. therefore, studies of bdv could provide a valuable model to inves ...201526923969
borna disease virus and deficit schizophrenia.it is controversial whether borna disease virus (bdv) infects humans and causes psychiatric disorders.200326983654
no borna disease virus-specific rna detected in blood of race horses and jockeys.borna disease virus (bdv) predominantly infects horses and sheep, causing a broad range of behavioural disorders. it is controversial whether bdv infects humans and causes psychiatric disorders.200626989971
long-term expression of mirna for rna interference using a novel vector system based on a negative-strand rna virus.rna interference (rnai) has emerged as a promising technique for gene therapy. however, the safe and long-term expression of small rna molecules is a major concern for the application of rnai therapies in vivo. borna disease virus (bdv), a non-segmented, negative-strand rna virus, establishes a persistent infection without obvious cytopathic effects. unique among animal non-retroviral rna viruses, bdv persistently establishes a long-lasting persistent infection in the nucleus. these features mak ...201627189575
the pathogenesis of bornaviral diseases in mammals.natural bornavirus infections and their resulting diseases are largely restricted to horses and sheep in central europe. the disease also occurs naturally in cats, and can be induced experimentally in laboratory rodents and numerous other mammals. borna disease virus-1 (bodv-1), the cause of most cases of mammalian borna disease, is a negative-stranded rna virus that replicates within the nucleus of target cells. it causes severe, often lethal, encephalitis in susceptible species. recent events, ...201627212192
sero-epidemiological analysis of vertical transmission relative risk of borna disease virus infection in dairy herds.borna disease virus (bdv) is a virus that causes a neurological disease in domestic animals, including a variety of animal species in japan. few studies have examined the mode of transmission of this virus in cattle, and the exact mechanisms underlying the transmission of the virus need to be elucidated. this study aimed to examine the contribution of vertical transmission of the virus, which occurs when the virus is transmitted from the mother to offspring during gestation or birth. we used an ...201627498995
endogenous non-retroviral rna virus elements evidence a novel type of antiviral immunity.vertebrate genomes contain many virus-related sequences derived from both retroviruses and non-retroviral rna and dna viruses. such non-retroviral rna sequences are possibly produced by reverse-transcription and integration of viral mrnas of ancient rna viruses using retrotransposon machineries. we refer to this process as transcript reversion. during an ancient bornavirus infection, transcript reversion may have left bornavirus-related sequences, known as endogenous bornavirus-like nucleoprotei ...201727510928
screening red foxes (vulpes vulpes) for possible viral causes of encephalitis.next to various known infectious and non-infectious causes, the aetiology of non-suppurative encephalitis in red foxes (vulpes vulpes) often remains unclear. known causes in foxes imply rabies, canine distemper, toxoplasmosis, aujeszky's disease, as well as parvovirus, adenovirus, circovirus and flavivirus infections. in this study, particular attention was paid on bornaviruses, since red foxes are predators of bicoloured white-toothed shrews, a reservoir of borna disease virus 1 (bodv-1). in ad ...201627590473
identification and bioinformatic analysis of dysregulated micrornas in human oligodendroglial cells infected with borna disease virus.micrornas (mirnas) are recognized as important regulators of gene expression via translational depression or mrna degradation. previously, dysregulated mirnas have been found in neurodegenerative and neuropsychiatric disorders. borna disease virus (bdv) is a neurotropic, negative single‑stranded rna virus, which may be a cause of human neuropsychiatric disease. bdv is regarded as an ideal model to analyze the molecular mechanisms of mental disorders caused by viral infection. in the present stud ...201627748825
intranasal location and immunohistochemical characterization of the equine olfactory epithelium.the olfactory epithelium (oe) is the only body site where neurons contact directly the environment and are therefore exposed to a broad variation of substances and insults. it can serve as portal of entry for neurotropic viruses which spread via the olfactory pathway to the central nervous system. for horses, it has been proposed and concluded mainly from rodent studies that different viruses, e.g., borna disease virus, equine herpesvirus 1 (ehv-1), hendra virus, influenza virus, rabies virus, v ...201627790096
detection of antibodies against borna disease virus proteins in an autistic child and her mother. 201727795475
borna disease virus assembles porous cage-like viral factories in the nucleus.animal-derived rna viruses frequently generate viral factories in infected cells. however, the details of how rna viruses build such intracellular structures are poorly understood. in this study, we examined the structure and formation of the viral factories, called viral speckle of transcripts (vspots), that are produced in the nuclei of host cells by borna disease virus (bdv). super-resolution microscopic analysis showed that bdv assembled vspots as intranuclear cage-like structures with 59-18 ...201627803166
primary psychosis and borna disease virus infection in lithuania: a case control study.the hypothesis that microbial infections may be linked to mental disorders has long been addressed for borna disease virus (bdv), but clinical and epidemiological evidence remained inconsistent due to non-conformities in detection methods. bdv circulating immune complexes (cic) were shown to exceed the prevalence of serum antibodies alone and to comparably screen for infection in europe (de, cz, it), the middle east (ir) and asia (cn), still seeking general acceptance.201627809822
change in the responsiveness of interferon-stimulated genes during early pregnancy in cows with borna virus-1 infection.borna disease virus is a neurotropic pathogen and infects the central nervous system. this virus infected a variety of animal species including cows. the most of cows infected with borna disease virus 1 (bodv-1) exhibit subclinical infection without any neurological symptoms throughout their lifetime. we previously reported on the low conception rates in-seropositive cows. interferon-τ (ifn-τ) plays an important role in stable fertilization, and is produced from the fetal side following embryo g ...201627842550
identification of suitable reference genes for bdv-infected primary rat hippocampal neurons.borna disease virus (bdv) is a neurotropic rna virus that infects the limbic system of mammals and results in behavioral disorders. the hippocampus is a core region in the limbic system, which contributes to memory and learning and is important in the regulation of emotion. however, no validated microrna housekeeping genes have yet been identified in bdv‑infected rat primary hippocampal neurons. proper normalization is key in accurate mirna expression analysis. the present study used reverse tra ...201627878262
neuronal retrograde transport of borna disease virus occurs in signalling endosomes.long-range axonal retrograde transport is a key mechanism for the cellular dissemination of neuroinvasive viruses, such as borna disease virus (bdv), for which entry and egress sites are usually distant from the nucleus, where viral replication takes place. although bdv is known to disseminate very efficiently in neurons, both in vivo and in primary cultures, the modalities of its axonal transport are still poorly characterized. in this work, we combined different methodological approaches, such ...201627902378
detection of borna disease virus (bdv) in patients with first episode of schizophrenia.objective: schizophrenia is a complex widespread neuropsychiatric disorder. this illness encompasses a complex debilitating mental disorder causing illusion, delusion, disturbed relationship, low motivation and decline of emotion. viral infection of the brain including borna disease virus (bdv) may play a role in transient or permanent neurological and behavioral abnormalities. this role of borna virus has not been resolved outright yet, and based on published papers investigation examining the ...201628050187
pathological findings in the red fox (vulpes vulpes), stone marten (martes foina) and raccoon dog (nyctereutes procyonoides), with special emphasis on infectious and zoonotic agents in northern germany.anthropogenic landscape changes contributed to the reduction of availability of habitats to wild animals. hence, the presence of wild terrestrial carnivores in urban and peri-urban sites has increased considerably over the years implying an increased risk of interspecies spillover of infectious diseases and the transmission of zoonoses. the present study provides a detailed characterisation of the health status of the red fox (vulpes vulpes), stone marten (martes foina) and raccoon dog (nyctereu ...201728399176
central nervous system infection with borna disease virus causes kynurenine pathway dysregulation and neurotoxic quinolinic acid production.central nervous system infection of neonatal and adult rats with borna disease virus (bdv) results in neuronal destruction and behavioral abnormalities with differential immune-mediated involvement. neuroactive metabolites generated from the kynurenine pathway of tryptophan degradation have been implicated in several human neurodegenerative disorders. here, we report that brain expression of key enzymes in the kynurenine pathway are significantly, but differentially, altered in neonatal and adul ...201728446679
antiviral activity of favipiravir (t-705) against mammalian and avian bornaviruses.bornaviruses, non-segmented, negative-strand rna viruses, are emerging agents with the potential for causing various types of neurological symptoms. previous studies have shown that ribavirin, a nucleic acid analog with broad-spectrum antiviral activity, has a potent antiviral effect on infections with a mammalian bornavirus, borna disease virus (bodv-1), as well as avian bornaviruses. however, ribavirin-based treatment does not eliminate bornaviruses from persistently infected cells and viral r ...201728465146
primary central nervous system diffuse large b-cell lymphoma shows an activated b-cell-like phenotype with co-expression of c-myc, bcl-2, and bcl-6.diffuse large b-cell lymphoma (dlbcl) is the most common non-hodgkin lymphoma, whose main prognostic factor is closely related to germinal center b-cell-like subtype (gcb- dlbcl) or activated b-cell-like type (non-gcb-dlbcl). the most common type of primary central nervous system lymphoma is diffuse large b-cell type with poor prognosis and the reason is unclear. this study aims to stratify primary central nervous system diffuse large b-cell lymphoma (pcns-dlbcl) according to the cell-of-origin ...201728552541
infections of horses and shrews with bornaviruses in upper austria: a novel endemic area of borna disease.borna disease, a lethal infection with borna disease virus-1 (bodv-1), was diagnosed in four horses from upper austria in 2015 and 2016. all cases occurred in winter (two cases in february 2015 and two cases in december 2016), and the maximal distance of the affected stables was 17 km. to demonstrate whether the causative agent was also harbored by its reservoir host, the bicolored white-toothed shrew (crocidura leucodon), 28 shrews from this geographic area were collected in 2015 and investigat ...201728634359
dual function of the nuclear export signal of the borna disease virus nucleoprotein in nuclear export activity and binding to viral phosphoprotein.borna disease virus (bodv), which has a negative-sense, single-stranded rna genome, causes persistent infection in the cell nucleus. the nuclear export signal (nes) of the viral nucleoprotein (n) consisting of leucine at positions 128 and 131 and isoleucine at positions 133 and 136 overlaps with one of two predicted binding sites for the viral phosphoprotein (p). a previous study demonstrated that higher expression of bodv-p inhibits nuclear export of n; however, the function of n nes in the int ...201728693611
linkage between the leader sequence and leader rna production in borna disease virus-infected cells.the 3'-untranslated region (utr) of the non-segmented, negative-strand (nns) rna viral genome is called the leader sequence, and functions as the promoter for viral replication and transcription. nns rna viruses also use the sequence as a template to synthesize leader rnas (lernas) with unknown functions. borna disease virus (bdv) is unique because it establishes a persistent infection and replicates in the nucleus. no report has yet demonstrated the presence of lernas during bdv infection. here ...201728715652
generation of a non-transmissive borna disease virus vector lacking both matrix and glycoprotein genes.borna disease virus (bodv), a prototype of mammalian bornavirus, is a non-segmented, negative strand rna virus that often causes severe neurological disorders in infected animals, including horses and sheep. unique among animal rna viruses, bodv transcribes and replicates non-cytopathically in the cell nucleus, leading to the establishment of a long-lasting persistent infection. this striking feature of bodv indicates its potential as an rna virus vector system. in a previous study, we demonstra ...201728776750
detection of antibodies against borna disease virus proteins in an autistic child and her mother.volume 70, no 2, p.225-227, 2017. page 226, figure 1b and c should appear as shown below.201728943599
different inhibitory effects on the proliferation and apoptosis of human and laboratory borna disease virus‑infected human neuroblastoma sh‑sy5y cells in vitro.borna disease virus (bdv) is a neurotropic and non‑cytolytic virus, which causes behavioral disorders in a wide range of warm‑blooded species. it is well established that bdv induces neurodegeneration by impairing neurogenesis and interfering with neuronal functioning in the limbic system. in the present study, the potential role of bdv infection in sh‑sy5y cells was identified, and comparisons of two original bdv strains (the human hu‑h1 and the laboratory strain v) were performed to further el ...201829115502
no molecular evidence of borna disease virus among schizophrenia and bipolar disorder patients in iran.viruses have been suggested as one of the risk factors for psychiatric disorders. among infectious agents borna disease virus (bdv) has been known as a neurotropic virus which is able to cause neurological disorders in different animals. recently there were controversial findings about bdv association with pathogenesis of human psychotic disorders.201729214003
potential links between hepadnavirus and bornavirus sequences in the host genome and cancer.various viruses leave their sequences in the host genomes during infection. such events occur mainly in retrovirus infection but also sometimes in dna and non-retroviral rna virus infections. if viral sequences are integrated into the genomes of germ line cells, the sequences can become inherited as endogenous viral elements (eves). the integration events of viral sequences may have oncogenic potential. because proviral integrations of some retroviruses and/or reactivation of endogenous retrovir ...201729312227
application of antibodies against borna disease virus phosphoprotein and nucleoprotein on paraffin sections.in order to study the application of antibodies against recombinant proteins for detecting borna disease virus (bdv) phosphoprotein (p24) and nucleoprotein (p40) (bdv‑p24/p40) on paraffin sections by immunohistochemistry. the purified fusion p24 and p40 proteins were used for the preparation of polyclonal and monoclonal anti‑p24 and anti‑40 antibodies, which were confirmed by elisa and western blotting. paraffin sections were made from bdv‑infected sprague‑dawley (sd) rats (n=20), pbs‑injected s ...201829363723
hippocampal expression of a virus-derived protein impairs memory in mice.the analysis of the biology of neurotropic viruses, notably of their interference with cellular signaling, provides a useful tool to get further insight into the role of specific pathways in the control of behavioral functions. here, we exploited the natural property of a viral protein identified as a major effector of behavioral disorders during infection. we used the phosphoprotein (p) of borna disease virus, which acts as a decoy substrate for protein kinase c (pkc) when expressed in neurons ...201829378968
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