Bornavirus Infection Research Articles

Intracerebral Borna Disease Virus Infection of Bank Voles Leading to Peripheral Spread and Reverse Transcription of Viral RNA

Bornaviruses, which chronically infect many species, can cause severe neurological diseases in some animal species; their association with human neuropsychiatric disorders is, however, debatable. The epidemiology of Borna disease virus (BDV), as for other members of the family Bornaviridae, is largely unknown, although evidence exists for a reservoir in small mammals, for example bank voles (Myodes glareolus). In addition to the current exogenous infections and despite the fact that bornaviruses have an RNA genome, bornavirus sequences integrated into the genomes of several vertebrates millions of years ago. Our hypothesis is that the bank vole, a common wild rodent species in traditional BDV-endemic areas, can serve as a viral host; we therefore explored whether this species can be infected with BDV, and if so, how the virus spreads and whether viral RNA is transcribed into DNA in vivo.We infected neonate bank voles intracerebrally with BDV and euthanized them 2 to 8 weeks post-infection. Specific Ig antibodies were detectable in 41%. Histological evaluation revealed no significant pathological alterations, but BDV RNA and antigen were detectable in all infected brains. Immunohistology demonstrated centrifugal spread throughout the nervous tissue, because viral antigen was widespread in peripheral nerves and ganglia, including the mediastinum, esophagus, and urinary bladder. This was associated with viral shedding in feces, of which 54% were BDV RNA-positive, and urine at 17%. BDV nucleocapsid gene DNA occurred in 66% of the infected voles, and, surprisingly, occasionally also phosphoprotein DNA. Thus, intracerebral BDV infection of bank vole led to systemic infection of the nervous tissue and viral excretion, as well as frequent reverse transcription of the BDV genome, enabling genomic integration. This first experimental bornavirus infection in wild mammals confirms the recent findings regarding bornavirus DNA, and suggests that bank voles are capable of bornavirus transmission.

Occurrence of avian bornavirus infection in captive psittacines in various European countries and its association with proventricular dilatation disease

A total of 1442 live birds and 73 dead birds out of 215 bird collections in Spain, Germany, Italy, the UK and Denmark were tested for avian bornavirus (ABV) infection by four different methods. The majority of the birds were psittacines belonging to 54 different genera of the order Psittaciformes. In total, 22.8% of the birds reacted positive for ABV in at least one of the tests. Combined testing of swabs from the crop and cloaca, and serum for the diagnosis of ABV infection in live birds revealed that virus shedding and antibody production coincided in only one-fifth of the positive birds so that the examination of these three samples is recommended for reliable ABV diagnosis. By statistical analysis of this large number of samples, the ABV infection proved to be highly significant (P <0.001) associated with histopathologically confirmed proventricular dilatation disease (PDD) in dead birds as well as with clinically assumed PDD in live birds. However, ABV infection was also detected in psittacines without pathological lesions or clinical signs of PDD. Twelve non-psittacine birds belonging to the genera Aburria, Ciconia, Geopelia, Leucopsar and Pavo were tested negative for ABV infection. Within the order of Psittaciformes, birds belonging to 33 different genera reacted positive for ABV. In 16 of these psittacine genera, the ABV infection was demonstrated for the first time. The present study emphasizes the widespread occurrence of clinically variable ABV infections in Europe by analysing a large number of specimens from a broad range of bird species in several assays.

Diagnosis of Avian bornavirus infection in psittaciformes by serum antibody detection and reverse transcription polymerase chain reaction assay using feather calami

Avian bornavirus (ABV) is the causative agent of proventricular dilatation disease (PDD), a highly devastating and contagious disease of psittacines (parrots and parakeets), which has resulted in the death of many captive birds. Accurate diagnosis of bornavirus infection is therefore important for the identification and isolation of infected birds. The current study showed that nonvascular contour (chest) feather calami provide a ready and minimally invasive source of RNA for the detection of ABV by reverse transcription polymerase chain reaction (RT-PCR). Storage of the feathers at room temperature for at least a month did not affect the results. Serological analysis by enzyme-linked immunosorbent assay (ELISA) showed that identification of anti-bornaviral nucleoprotein P40 antibodies can identify many birds with a past or present infection. The presence of anti-avian bornaviral P24 phosphoprotein and P16 matrix protein antibodies was quite variable, rendering these antibodies less useful for diagnosis of ABV infection. The significance of the present findings is that the use of nonvascular feathers as a source of RNA allows sample collection under conditions where storage of other samples would be difficult. Serum detection by ELISA of anti-P40 antibodies allows the identification of infected birds when RT-PCR fails.

Proventricular Dilatation Disease Associated with Avian Bornavirus Infection in a Citron-Crested Cockatoo that Was Born and Hand-Reared in Japan

A 5-month-old female Citron-crested Cockatoo (Cacatua sulphurea citrinocristata) that was born and hand-reared in Japan died with suspected proventricular dilatation disease (PDD). Macroscopic and microscopic examinations of the bird revealed characteristic features of PDD, i.e., distention of the proventriculus and infiltration of lymphocytes and plasma cells in ganglia of various organs and in central and peripheral nerves. A linkage of this PDD case to infection with avian bornavirus (ABV) was documented by RT-PCR amplification of the virus genomes from the affected bird. Phylogenetic analysis revealed that the ABV identified in this study clustered into the genotype 2, which is one of the dominant ABV genotypes worldwide. To the best of our knowledge, this is the first report of a natural case of PDD associated with ABV infection in Japan.

Proventricular Dilatation Disease Associated with Avian Bornavirus in a Scarlet Macaw (Ara Macao)

A case of proventricular dilatation disease is described in a scarlet macaw (Ara macao) from clinical presentation to diagnosis with molecular methods. The initial clinical signs were depression progressing to head pressing over several days. A leukocytosis with toxic heterophil changes, hypoalbuminemia, and increased serum activity of aspartate aminotransferase and creatine kinase were present. Lead and zinc assays were within reference ranges, and results from Chlamydophila and polyomavirus testing were negative. Contrast-enhanced fluoroscopy revealed normal gastrointestinal transit times and motility as well as the presence of 2 small metallic foreign bodies in the ventriculus. The macaw was treated with antimicrobials, analgesics, vitamins E and B complex, force-feeding, and fluid administration with little improvement. Euthanasia was elected, and histologic examination of brain tissue revealed a perivascular lymphoplasmacytic infiltration, while the lungs had evidence of a fungal pneumonia. Tissue samples from the brain and proventriculus tested positive for the presence of Avian bornavirus genotype 2, while serology confirmed Avian bornavirus infection.

Posterior segment diseases

Diseases of the vitreous, fundus and optic nerve are described and illustrated according to their ophthalmological appearance. Vitreal alterations are commonly of developmental, degenerative, age related, traumatic or inflammatory origin and of minor clinical relevance. In contrast, those affecting the fundus, may be accompanied by visual deficits or blindness. Fundic lesions of inflammatory (multifocal or peripapillary chorioretinitis, haemorrhage, retinal detachment) and traumatic origin have to be differentiated from congenital (congenital stationary night blindness, colobomatous defects, retinal dysplasia), degenerative (cystic retinal degeneration), metabolic (equine motor neuron disease), neoplastic and age related alterations (senile retinopathy). Inflammation (acute neurochorioretinitis) and ischaemia (ischaemic neuro-chorioretinopathy) involving the optic nerve will lead to blindness. The optic disc can be aplastic/hypoplastic or excavated due to coloboma or glaucoma, affected by ligation of the carotid and palatine arteries. Optic disc masses may arise due to inflammation, severe systemic haemorrhage, neoplasia or trauma. Lesions of the retrobulbar optic nerve can be caused by Borna virus infection, fungal granuloma, toxic insult, halicephalobiasis, trauma, severe blood loss and infection of the sphenopalatine sinus.

Analysis of Naturally Occurring Avian Bornavirus Infection and Transmission during an Outbreak of Proventricular Dilatation Disease among Captive Psittacine Birds

A proventricular dilatation disease (PDD) outbreak provided the opportunity to investigate the transmissibility of avian Bornavirus (ABV) and its linkage to PDD under natural conditions. Upon exposure to a bird with a fatal case of PDD, 10 birds became symptomatic and died. ABV2 RNA was recovered from available tissues. Further screening revealed that 12/46 exposed birds were ABV2(+). Three chicks boarded at this aviary developed PDD. They harbored the same ABV2 isolate and transmitted it to five of eight chicks in their home aviary. These findings demonstrate that ABV infection precedes the development of PDD. ABV-specific Western blotting and reverse transcription-PCR indicate that ABV2 is not strictly neurotropic.

Experimental induction of proventricular dilatation disease in cockatiels (Nymphicus hollandicus) inoculated with brain homogenates containing avian bornavirus 4

BackgroundProventricular dilatation disease (PDD) is a fatal disorder of psittacine birds worldwide. The disease is characterized by lymphoplasmacytic infiltration of the central and peripheral nervous systems, leading to gastrointestinal motility and/or central nervous system dysfunction. Recently, we detected a significant association between avian bornavirus (ABV) infection and clinical signs of PDD in psittacines. However, it remains unclear whether ABV infection actually causes PDD. To address this question, we examined the impact of ABV inoculation on the cockatiel (Nymphicus hollandicus).ResultsFive cockatiels were inoculated via multiple routes (intramuscular, intraocular, intranasal, and oral) with a brain homogenate derived from either a PDD(+) avian bornavirus 4 (ABV4) (+) case (n = 3 inoculees) or from a PDD(-) ABV(-) control (n = 2 inoculees). The control birds remained free of clinical or pathological signs of PDD, and tested ABV(-) by RT-PCR and immunohistochemistry (IHC). In contrast, all three cockatiels inoculated with ABV4(+) brain homogenate developed gross and microscopic PDD lesions, and two exhibited overt clinical signs. In numerous tissues, ABV RT-PCR and sequence analysis demonstrated the presence of ABV4 RNA nearly identical to that in the inoculum. ABV was detected in the central nervous system of the three ABV-inoculees by IHC. Pyrosequencing to investigate the viral flora in the ABV4(+) inoculum uncovered 7 unique reads sharing 73–100% nucleotide sequence identity with previously identified ABV sequences and 24 reads sharing 40–89% amino acid sequence identity with viruses in the Retroviridae and Astroviridae families. Of these candidate viral species, only ABV RNA was recovered from tissues of the inoculated birds.ConclusionIn this study, the clinical and pathological manifestations of PDD were induced by inoculation of cockatiels with brain homogenates containing avian bornavirus 4. By using high throughput pyrosequencing an in-depth view of the viral content of the inoculum was achieved, revealing that of 3 candidate virus families detected, only the presence of ABV RNA correlated with the development of PDD. This study provides evidence of a causal association between ABV4 infection and PDD in cockatiels.

Horses diagnosed clinically and by laboratory methods for Bornavirus infection and treated with amantadine: “Patients” of the Tierärztliche Klinik für Pferde in Meerbusch

APMISVolume 116, Issue s124 p. 44-45 Horses diagnosed clinically and by laboratory methods for Bornavirus infection and treated with amantadine: “Patients” of the Tierärztliche Klinik für Pferde in Meerbusch Case report J. C. MERKT, Corresponding Author J. C. MERKTCorresponding author: e-mail: [email protected]Search for more papers by this authorR. WEBER, R. WEBER Tierärztliche Klinik für Pferde, Meerbusch, GermanySearch for more papers by this author J. C. MERKT, Corresponding Author J. C. MERKTCorresponding author: e-mail: [email protected]Search for more papers by this authorR. WEBER, R. WEBER Tierärztliche Klinik für Pferde, Meerbusch, GermanySearch for more papers by this author First published: 13 October 2008 https://doi.org/10.1111/j.1600-0463.2008.000m5.xRead the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL No abstract is available for this article. Volume116, Issues124June 2008Pages 44-45 RelatedInformation

Human Bornavirus infection – towards a valid diagnostic system

APMISVolume 116, Issue s124 p. 21-39 Human Bornavirus infection – towards a valid diagnostic system LIV BODE, Corresponding Author LIV BODE * Disclaimer: the article reflects the author's but not the institution's opinion (see also http:www.rki.de). This article is in part an evaluation and assessment of results which will be published elsewhere in detail. Contributions of unpublished raw data included here were from the Master Theses of Thomas Willemsen (epitopes on BDV N- and P-protein), Dennis Schmidt (BDV N-protein characterisation from plasma), and Steffen Zander (BDV P-protein).Corresponding author: E-mail (office): [email protected]E-mail (Internet): [email protected]Search for more papers by this author LIV BODE, Corresponding Author LIV BODE * Disclaimer: the article reflects the author's but not the institution's opinion (see also http:www.rki.de). This article is in part an evaluation and assessment of results which will be published elsewhere in detail. Contributions of unpublished raw data included here were from the Master Theses of Thomas Willemsen (epitopes on BDV N- and P-protein), Dennis Schmidt (BDV N-protein characterisation from plasma), and Steffen Zander (BDV P-protein).Corresponding author: E-mail (office): [email protected]E-mail (Internet): [email protected]Search for more papers by this author First published: 13 October 2008 https://doi.org/10.1111/j.1600-0463.2008.000m3.xCitations: 21 Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat Citing Literature Volume116, Issues124June 2008Pages 21-39 RelatedInformation

Human Bornavirus infections, diagnosis and therapy

Human Bornavirus infections, diagnosis and therapy

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 intriguing model for tardive dyskinesia and dystonic syndromes. The neuropathologic, physiologic, and neurobehavioral features of BDV infection of neonates indicate that it not only provides a useful model for exploring the mechanisms by which viral and immune factors may damage developing neurocircuitry, but also has significant links to the range of biologic, neurostructural, locomotor, cognitive, and social deficits observed in serious neuropsychiatric illnesses such as autism.

High seroprevalence of Borna virus infection in schizophrenic patients, family members and mental health workers in Taiwan.

Borna disease virus (BDV), a negative-strand RNA virus, has been reported to be associated with severe psychiatric disorders. The association is mainly based on the findings that patients with schizophrenia and depression have a higher seroprevalence rate of BDV-specific antibodies than controls. In addition, psychiatric patients were also found to have a higher detection rate of BDV transcripts in their blood than controls. By using an improved Western blot analysis, we first demonstrated that Chinese schizophrenic patients from Taiwan also have a higher seroprevalence of BDV-specific antibodies than controls (12.1% vs 2.9%, P< 0.001), providing support to the positive association between BDV and psychiatric disorders in our population. Because of the contagious nature of viral infection, we further examined patients' family members and mental health workers, who have close contact with patients. We found that both groups also have a higher seroprevalence of BDV-specific antibodies, 12.1% and 9.8%, respectively, than controls. This finding provides some evidence for a possible human-to-human transmission of Borna disease virus. Our finding needs further independent verification from other research groups and the clinical relevance of this preliminary observation deserves further study.

Prenatal exposure to 1957 influenza pandemic and non-affective psychosis in The Netherlands

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 in cats, including etiological agent, clinical signs, pathogenesis, epidemiology and diagnostics, with comparisons to Bornavirus infections in other species.

Borna virus infections in cattle associated with fatal neurological disease.

Borna virus infections in cattle associated with fatal neurological disease.

Persistent infections caused by Borna virus.

Pathogenical investigations on Borna disease (enzootic meningoencephalomyelitis of horses and sheep) became possible after we successfully cultivated the virus in cell cultures and adapted the fluorescent antibody technique for the detection of virus antigen and for quantitative assessments. According to our experiences Borna infections occur in two main forms: 1. acute or subacute disease, sometimes in a subclinical form; 2. persistent infection in different forms: a) chronic disease, b) tolerated infection, c) latent infection (possibly). One of the main characteristics of the virus persistence in vivo and in vitro is a relatively short latent phase prior to the continuous virus multiplication in the infected systems. Virus persistence can be demonstrated in the CNS over several months or years in infected animals. Sera from those animals show complement-fixing antibody activity in various amounts during the observation time. In infected cell cultures, the virus likewise persists several months or longer without producing a cytopathic effect. The possibility of vertical virus transmission under field conditions in horses is pointed out. The host spectrum of Borna virus is wide, and potential spread to man is discussed. The persistent form of Borna virus infection in animals and cell cultures sheds new light upon certain aspects of the pathogenesis of Borna disease. Furthermore, the Borna infection may in the future be a useful model for studying slow and persistent virus infections.