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Christiane Herden - One of the best experts on this subject based on the ideXlab platform.
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age dependent development and clinical characteristics of an experimental parrot Bornavirus 4 pabv 4 infection in cockatiels nymphicus hollandicus
Avian Pathology, 2021Co-Authors: Anna Maria Gartner, Sibylle Herzog, Dirk Enderlein, Christiane Herden, Sara Malberg, Jessica Link, Bianca Bucking, J Petzold, Michael LierzAbstract:Parrot Bornavirus (PaBV) is a pathogen often found in psittacine populations. Infected, clinically healthy carrier birds are of major importance for epidemiology, but the underlying pathomechanism ...
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first isolation in vivo and genomic characterization of zoonotic variegated squirrel Bornavirus 1 vsbv 1 isolates
Emerging microbes & infections, 2020Co-Authors: Kore Schlottau, Martin Beer, Christiane Herden, Daniel Nobach, Stefan Finke, Donata HoffmannAbstract:The variegated squirrel Bornavirus 1 (VSBV-1), a member of the family Bornaviridae, was discovered in 2015 in a series of lethal human infections. Screening approaches revealed kept exotic squirrel...
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update on immunopathology of Bornavirus infections in humans and animals
Advances in Virus Research, 2020Co-Authors: Daniel Nobach, Jana Muller, Dennis Tappe, Christiane HerdenAbstract:Abstract Knowledge on Bornaviruses has expanded tremendously during the last decade through detection of novel Bornaviruses and endogenous Bornavirus-like elements in many eukaryote genomes, as well as by confirmation of insectivores as reservoir species for classical Borna disease virus 1 (BoDV-1). The most intriguing finding was the demonstration of the zoonotic potential of lethal human Bornavirus infections caused by a novel Bornavirus of different squirrel species (variegated squirrel 1 Bornavirus, VSBV-1) and by BoDV-1 known as the causative agent for the classical Borna disease in horses and sheep. Whereas a T cell-mediated immunopathology has already been confirmed as key disease mechanism for infection with BoDV-1 by experimental studies in rodents, the underlying pathomechanisms remain less clear for human Bornavirus infections, infection with other Bornaviruses or infection of reservoir species. Thus, an overview of current knowledge on the pathogenesis of Bornavirus infections focusing on immunopathology is given.
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Recombinant Modified Vaccinia Virus Ankara (MVA) Vaccines Efficiently Protect Cockatiels Against Parrot Bornavirus Infection and Proventricular Dilatation Disease.
Viruses, 2019Co-Authors: Isabell Rall, Christiane Herden, Ralf Amann, Sara Malberg, Dennis RubbenstrothAbstract:Parrot Bornaviruses (PaBVs) are the causative agents of proventricular dilatation disease (PDD), a chronic and often fatal neurologic disorder in Psittaciformes. The disease is widely distributed in private parrot collections and threatens breeding populations of endangered species. Thus, immunoprophylaxis strategies are urgently needed. In previous studies we demonstrated a prime-boost vaccination regime using modified vaccinia virus Ankara (MVA) and Newcastle disease virus (NDV) constructs expressing the nucleoprotein and phosphoprotein of PaBV-4 (MVA/PaBV-4 and NDV/PaBV-4, respectively) to protect cockatiels (Nymphicus hollandicus) against experimental challenge infection. Here we investigated the protective effect provided by repeated immunization with either MVA/PaBV-4, NDV/PaBV-4 or Orf virus constructs (ORFV/PaBV-4) individually. While MVA/PaBV-4-vaccinated cockatiels were completely protected against subsequent PaBV-2 challenge infection and PDD-associated lesions, the course of the challenge infection in NDV/PaBV-4- or ORFV/PaBV-4-vaccinated birds did not differ from the unvaccinated control group. We further investigated the effect of vaccination on persistently PaBV-4-infected cockatiels. Remarkably, subsequent immunization with MVA/PaBV-4 and NDV/PaBV-4 neither induced obvious immunopathogenesis exacerbating the disease nor reduced viral loads in the infected birds. In summary, we demonstrated that vaccination with MVA/PaBV-4 alone is sufficient to efficiently prevent PaBV-2 challenge infection in cockatiels, providing a suitable vaccine candidate against avian Bornavirus infection and Bornavirus-induced PDD.
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variegated squirrel Bornavirus 1 in squirrels germany and the netherlands
Emerging Infectious Diseases, 2017Co-Authors: Kore Schlottau, Dirk Höper, Maria Jenckel, Judith M A Van Den Brand, Christine Fast, Christiane Herden, Jens Thielebein, Niels Mensing, Timo Homeierbachmann, Bert DienderAbstract:We screened squirrels in Germany and the Netherlands for the novel zoonotic variegated squirrel Bornavirus 1 (VSBV-1). The detection of VSBV-1 in 11 squirrels indicates a considerable risk for transmission to humans handling those animals. Therefore, squirrels in contact with humans should routinely be tested for VSBV-1.
Ian Tizard - One of the best experts on this subject based on the ideXlab platform.
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Treatment With Nonsteroidal Anti-Inflammatory Drugs Fails To Ameliorate Pathology In Cockatiels Experimentally Infected With Parrot Bornavirus-2
Veterinary medicine (Auckland N.Z.), 2019Co-Authors: Paulina Escandon, H L Shivaprasad, Jianhua Guo, J. Jill Heatley, Ian Tizard, Jeffrey M. B. MusserAbstract:Purpose Parrot Bornavirus is the etiological agent of Parrot Bornavirus syndrome, also referred to and comprising proventricular dilatation disease or PDD, macaw wasting disease, enteric ganglioneuritis and encephalitis, and avian ganglioneuritis. It has been suggested that nonsteroidal anti-inflammatory drugs may be able to ameliorate this disease. Therefore, this study investigated the effects of two commonly used nonsteroidal anti-inflammatory drugs, celecoxib and meloxicam, on cockatiels experimentally inoculated with Parrot Bornavirus-2 (PaBV-2). Materials and methods Twenty-seven cockatiels were randomized into 3 groups of 9 birds, matched with respect to historical PaBV shedding, weight, and sex. The cockatiels were inoculated with cell culture-derived PaBV-2 by the intranasal and intramuscular routes. Beginning at 23 days post-inoculation, birds in each group received oral treatment once daily with placebo, meloxicam (1.0 mg/kg), or celecoxib (10.0 mg/kg). Results Within 33-79 days post-inoculation, 2 birds died and 6 birds were euthanized based on neurological or gastrointestinal signs consistent with Parrot Bornavirus syndrome: 2 birds were euthanized in the placebo group, 1 bird died and 1 bird was euthanized in the meloxicam-treated group, and 1 bird died and 3 birds were euthanized in the celecoxib-treated group. Of these 8 birds, black intestinal contents were found upon necropsy in 2 birds of the meloxicam-treated group and 2 birds of the celecoxib-treated group. At day 173 (±2) post-inoculation, the remaining 19 birds were euthanized. Necropsy and histopathology showed lesions characteristic of Parrot Bornavirus syndrome in 23 cockatiels. Histopathologic lesions were present in birds of all 3 groups. There was no statistical difference between the groups nor was there a statistical difference among the 3 treatment groups in the detection of PaBV RNA and PaBV nucleoprotein using RT-PCR and immunohistochemistry, respectively. Conclusion Meloxicam and celecoxib treatments do not appear to alter the clinical presentation, viral shedding, gross lesions, histopathology, or viral distribution. Treatment with NSAIDs may cause gastrointestinal toxicity in cockatiels experimentally inoculated with PaBV-2.
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Studies on immunity and immunopathogenesis of parrot bornaviral disease in cockatiels.
Virology, 2017Co-Authors: Samer Sadeq Hameed, H L Shivaprasad, Ian Tizard, Susan PayneAbstract:Abstract We have demonstrated that vaccination of cockatiels (Nymphicus hollandicus) with killed parrot Bornavirus (PaBV) plus recombinant PaBV-4 nucleoprotein (N) in alum was protective against disease in birds challenged with a virulent Bornavirus isolate (PaBV-2). Unvaccinated birds, as well as birds vaccinated after challenge, developed gross and histologic lesions typical of proventricular dilatation disease (PDD). There was no evidence that vaccination either before or after challenge made the infection more severe. Birds vaccinated prior to challenge largely remained free of disease, despite the persistence of the virus in many organs. Similar results were obtained when recombinant N, in alum, was used for vaccination. In some rodent models, Borna disease is immune mediated thus we did an additional study whereby cyclosporine A was administered to unvaccinated birds starting 1 day prior to challenge. This treatment also conferred complete protection from disease, but not infection.
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The genome sequence of parrot Bornavirus 5
Virus Genes, 2015Co-Authors: Ian TizardAbstract:Although several new avian Bornaviruses have recently been described, information on their evolution, virulence, and sequence are often limited. Here we report the complete genome sequence of parrot Bornavirus 5 (PaBV-5) isolated from a case of proventricular dilatation disease in a Palm cockatoo ( Probosciger aterrimus ). The complete genome consists of 8842 nucleotides with distinct 5′ and 3′ end sequences. This virus shares nucleotide sequence identities of 69–74 % with other Bornaviruses in the genomic regions excluding the 5′ and 3′ terminal sequences. Phylogenetic analysis based on the genomic regions demonstrated this new isolate is an isolated branch within the clade that includes the aquatic bird Bornaviruses and the passerine Bornaviruses. Based on phylogenetic analyses and its low nucleotide sequence identities with other Bornavirus, we support the proposal that PaBV-5 be assigned to a new Bornavirus species:- Psittaciform 2 Bornavirus .
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swans in the Northeast United States
2015Co-Authors: Jianhua Guo, Ian Tizard, John A. Baroch, Jill J. Heatley, Lina Covaleda, Susan L Payne, Correspondence Ian TizardAbstract:Widespread avian Bornavirus infection in mut
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Ribavirin Inhibits Parrot Bornavirus 4 Replication in Cell Culture.
PloS one, 2015Co-Authors: Jeffrey M. B. Musser, Paulette F Suchodolski, Anastasia V. Koinis, Paulina Escandon, Ian TizardAbstract:Parrot Bornavirus 4 is an etiological agent of proventricular dilatation disease, a fatal neurologic and gastrointestinal disease of psittacines and other birds. We tested the ability of ribavirin, an antiviral nucleoside analog with antiviral activity against a range of RNA and DNA viruses, to inhibit parrot Bornavirus 4 replication in duck embryonic fibroblast cells. Two analytical methods that evaluate different products of viral replication, indirect immunocytochemistry for viral specific nucleoprotein and qRT-PCR for viral specific phosphoprotein gene mRNA, were used. Ribavirin at concentrations between 2.5 and 25 μg/mL inhibited parrot Bornavirus 4 replication, decreasing viral mRNA and viral protein load, in infected duck embryonic fibroblast cells. The addition of guanosine diminished the antiviral activity of ribavirin suggesting that one possible mechanism of action against parrot Bornavirus 4 may likely be through inosine monophosphate dehydrogenase inhibition. This study demonstrates parrot Bornavirus 4 susceptibility to ribavirin in cell culture.
Dennis Rubbenstroth - One of the best experts on this subject based on the ideXlab platform.
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active case finding of current Bornavirus infections in human encephalitis cases of unknown etiology germany 2018 2020
Emerging Infectious Diseases, 2021Co-Authors: Philip Eisermann, Dennis Rubbenstroth, Daniel Cadar, Corinna Thomebolduan, Petra Eggert, Alexander Schlaphof, Frank Leypoldt, Martin Stangel, Thorsten Fortwangler, Florian HoffmannAbstract:Human Bornavirus encephalitis is a severe and often fatal infection caused by variegated squirrel Bornavirus 1 (VSBV-1) and Borna disease virus 1 (BoDV-1). We conducted a prospective study of Bornavirus etiology of encephalitis cases in Germany during 2018-2020 by using a serologic testing scheme applied along proposed graded case definitions for VSBV-1, BoDV-1, and unspecified Bornavirus encephalitis. Of 103 encephalitis cases of unknown etiology, 4 Bornavirus infections were detected serologically. One chronic case was caused by VSBV-1 after occupational-related contact of a person with exotic squirrels, and 3 acute cases were caused by BoDV-1 in virus-endemic areas. All 4 case-patients died. Bornavirus etiology could be confirmed by molecular methods. Serologic testing for these cases was virus specific, discriminatory, and a practical diagnostic option for living patients if no brain tissue samples are available. This testing should be guided by clinical and epidemiologic suspicions, such as residence in virus-endemic areas and animal exposure.
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introduction and spread of variegated squirrel Bornavirus 1 vsbv 1 between exotic squirrels and spill over infections to humans in germany
Emerging microbes & infections, 2021Co-Authors: Daniel Cadar, Vanessa Schulze, Kore Schlottau, Dennis Rubbenstroth, Bernd Hoffmann, Valerie Allendorf, Rainer G Ulrich, Arnt Ebinger, Donata Hoffmann, Gabriele IsmerAbstract:The variegated squirrel Bornavirus 1 (VSBV-1) is a recently discovered emerging viral pathogen which causes severe and eventually fatal encephalitis in humans after contact to exotic squirrels in p...
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Recombinant Modified Vaccinia Virus Ankara (MVA) Vaccines Efficiently Protect Cockatiels Against Parrot Bornavirus Infection and Proventricular Dilatation Disease.
Viruses, 2019Co-Authors: Isabell Rall, Christiane Herden, Ralf Amann, Sara Malberg, Dennis RubbenstrothAbstract:Parrot Bornaviruses (PaBVs) are the causative agents of proventricular dilatation disease (PDD), a chronic and often fatal neurologic disorder in Psittaciformes. The disease is widely distributed in private parrot collections and threatens breeding populations of endangered species. Thus, immunoprophylaxis strategies are urgently needed. In previous studies we demonstrated a prime-boost vaccination regime using modified vaccinia virus Ankara (MVA) and Newcastle disease virus (NDV) constructs expressing the nucleoprotein and phosphoprotein of PaBV-4 (MVA/PaBV-4 and NDV/PaBV-4, respectively) to protect cockatiels (Nymphicus hollandicus) against experimental challenge infection. Here we investigated the protective effect provided by repeated immunization with either MVA/PaBV-4, NDV/PaBV-4 or Orf virus constructs (ORFV/PaBV-4) individually. While MVA/PaBV-4-vaccinated cockatiels were completely protected against subsequent PaBV-2 challenge infection and PDD-associated lesions, the course of the challenge infection in NDV/PaBV-4- or ORFV/PaBV-4-vaccinated birds did not differ from the unvaccinated control group. We further investigated the effect of vaccination on persistently PaBV-4-infected cockatiels. Remarkably, subsequent immunization with MVA/PaBV-4 and NDV/PaBV-4 neither induced obvious immunopathogenesis exacerbating the disease nor reduced viral loads in the infected birds. In summary, we demonstrated that vaccination with MVA/PaBV-4 alone is sufficient to efficiently prevent PaBV-2 challenge infection in cockatiels, providing a suitable vaccine candidate against avian Bornavirus infection and Bornavirus-induced PDD.
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Detection of Avian Bornavirus in Wild and Captive Passeriformes in Brazil.
Avian diseases, 2019Co-Authors: Natalia Azevedo Philadelpho, Dennis Rubbenstroth, Marta Brito Guimarães, Yamê Miniero Davies, L. F. N. Nuñez, Claudete S. Astolfi-ferreira, Silvana H. Santander Parra, Antonio José Piantino FerreiraAbstract:Avian Bornaviruses (ABVs) are the causative agents of proventricular dilatation disease (PDD), a fatal neurologic disease considered to be a major threat to psittacine bird populations. We performed a reverse transcription PCR survey to detect the presence of canary avian Bornavirus (CnBV) in birds of order Passeriformes related to different clinical manifestations, such as sudden death, neurologic signs, apathy, anorexia, excessive beak growth, and PDD. A total of 227 samples from captive and wild canaries were included, of which 80 samples were captive birds, comprising saffron finches (n = 71) and common canary (n = 9), and 147 samples were wild birds distributed among a variety of several species. Two samples from captive birds (2/80) were positive for ABV, and in wild birds, only one sample was positive for ABV. The positive samples were subjected to DNA sequencing, and only the CnBV-1 serotype was found, which was the first time it was detected outside of Germany (Austria/Hungary), where it was first detected in 2009. Phylogenetic analysis confirmed that avian Bornavirus serotype CnBV-1 is present in order Passeriformes in Brazil.
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Viral vector vaccines protect cockatiels from inflammatory lesions after heterologous parrot Bornavirus 2 challenge infection.
Vaccine, 2016Co-Authors: Solveig Runge, Marita Olbert, Peter Staeheli, Christiane Herden, Sara Malberg, Angela Römer-oberdörfer, Dennis RubbenstrothAbstract:Avian Bornaviruses are causative agents of proventricular dilatation disease (PDD), a chronic neurologic and often fatal disorder of psittacines including endangered species. To date no causative therapy or immunoprophylaxis is available. Our previous work has shown that viral vector vaccines can delay the course of homologous Bornavirus challenge infections but failed to protect against PDD when persistent infection was not prevented. The goal of this study was to refine our avian Bornavirus vaccination and infection model to better represent natural Bornavirus infections in order to achieve full protection against a heterologous challenge infection. We observed that parrot Bornavirus 2 (PaBV-2) readily infected cockatiels (Nymphicus hollandicus) by combined intramuscular and subcutaneous injection with as little as 102.7foci-forming units (ffu) per bird, whereas a 500-fold higher dose of the same virus administered via peroral and oculonasal route did not result in persistent infection. These results indicated that experimental Bornavirus challenge infections with this virus should be performed via the parenteral route. Prime-boost vaccination of cockatiels with Newcastle disease virus (NDV) and modified vaccinia virus Ankara (MVA) vectors expressing the nucleoprotein and phosphoprotein genes of PaBV-4 substantially blocked Bornavirus replication following parenteral challenge infection with 103.5ffu of heterologous PaBV-2. Only two out of six vaccinated birds had very low viral levels detectable in a few organs. As a consequence, only one vaccinated bird developed mild PDD-associated microscopic lesions, while mock-vaccinated controls were not protected against PaBV-2 infection and inflammation. Our results demonstrate that NDV and MVA vector vaccines can protect against invasive heterologous Bornavirus challenge infections and subsequent PDD. These vector vaccines represent a promising tool to combat avian Bornaviruses in psittacine populations.
Susan Payne - One of the best experts on this subject based on the ideXlab platform.
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Studies on immunity and immunopathogenesis of parrot bornaviral disease in cockatiels.
Virology, 2017Co-Authors: Samer Sadeq Hameed, H L Shivaprasad, Ian Tizard, Susan PayneAbstract:Abstract We have demonstrated that vaccination of cockatiels (Nymphicus hollandicus) with killed parrot Bornavirus (PaBV) plus recombinant PaBV-4 nucleoprotein (N) in alum was protective against disease in birds challenged with a virulent Bornavirus isolate (PaBV-2). Unvaccinated birds, as well as birds vaccinated after challenge, developed gross and histologic lesions typical of proventricular dilatation disease (PDD). There was no evidence that vaccination either before or after challenge made the infection more severe. Birds vaccinated prior to challenge largely remained free of disease, despite the persistence of the virus in many organs. Similar results were obtained when recombinant N, in alum, was used for vaccination. In some rodent models, Borna disease is immune mediated thus we did an additional study whereby cyclosporine A was administered to unvaccinated birds starting 1 day prior to challenge. This treatment also conferred complete protection from disease, but not infection.
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aquatic bird Bornavirus associated disease in free living canada geese branta canadensis in the northeastern usa
Journal of Wildlife Diseases, 2017Co-Authors: Maureen Murray, I R Tizard, Samuel H Jennings, H L Shivaprasad, Susan Payne, Julie C Ellis, Arnaud J Van Wettere, Kathleen M ObrienAbstract:Abstract During the winter of 2013–14, 22 Canada geese (Branta canadensis) were admitted to the Wildlife Clinic at the Cummings School of Veterinary Medicine at Tufts University with nonspecific neurologic abnormalities and emaciation. Five of these geese, along with three geese that were submitted dead, were evaluated via histopathology, immunohistochemistry, and reverse transcription PCR (RT-PCR) for Bornaviruses. Histopathologically, six of the eight birds had lymphoplasmacytic encephalitis. One bird, which also had encephalitis, had a dilated esophagus. Lead poisoning, West Nile virus, avian influenza, and avian paramyxovirus infection were excluded from the diagnosis. Brain tissue from all eight geese was positive for bornaviral N-antigen on immunohistochemistry. Frozen brain tissue from five birds was available for Bornavirus RT-PCR. Three of the five birds were positive for the Bornavirus M gene. Formalin-fixed paraffin-embedded brain tissue was evaluated on the remaining three geese via RT-PCR, wi...
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Avian Bornaviruses in North American Gulls
Journal of wildlife diseases, 2015Co-Authors: Jianhua Guo, H L Shivaprasad, Ian Tizard, John A. Baroch, Susan PayneAbstract:Avian Bornaviruses, recently de- scribed members of the family Bornaviridae, have been isolated from captive parrots and passerines as well as wild waterfowl in which they may cause lethal neurologic disease. We report detection of avian Bornavirus RNA in the brains of apparently healthy gulls. We tested 439 gull brain samples from 18 states, primarily in the northeastern US, using a reverse- transcriptase PCR assay with primers designed to detect a conserved region of the Bornavirus M gene. Nine birds yielded a PCR product of appropriate size. Sequencing of PCR products indicated that the virus was closely related to aquatic bird Bornavirus 1 (ABBV-1). Viral RNA was detected in Herring Gulls (Larus argenta- tus), Ring-billed Gulls (Larus delawarensis), and Laughing Gulls (Leucophaeus atricilla). Eight of the nine positive birds came from the New York/New Jersey area. One positive Herring Gull came from New Hampshire. Histopathologic examination of one well-pre- served brain from a Herring Gull from Union County New Jersey, showed a lymphocytic encephalitis similar to that observed in borna- virus-infected parrots and geese. Bornavirus N protein was confirmed in two Herring Gull brains by immunohistochemistry. Thus ABBV- 1 can infect gulls and cause encephalitic brain lesions similar to those observed in other birds.
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widespread avian Bornavirus infection in mute swans in the northeast united states
Veterinary Medicine : Research and Reports, 2012Co-Authors: Jianhua Guo, I R Tizard, John A. Baroch, Jill J. Heatley, Lina Covaleda, Susan PayneAbstract:Avian Bornavirus (ABV) matrix (M) genes were detected by RT-PCR on brain tissue obtained from 192 mute swans harvested from several Northeastern states. A RT-PCR product was detected in 45 samples. Sequencing of the PCR products confirmed the presence of ABV belonging to the 'goose' genotype. The prevalence of positive samples ranged from 28% in Michigan to 0% in northern New York State. Two Rhode Island isolates were cultured. Their M, N, and X-P gene sequences closely matched recently published sequences from Canada geese.
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Complete Genome Sequence of Avian Bornavirus Genotype 1 from a Macaw with Proventricular Dilatation Disease
Journal of virology, 2012Co-Authors: Negin Mirhosseini, Patricia L Gray, Ian Tizard, Susan PayneAbstract:Avian Bornaviruses (ABV) were first detected and described in 2008. They are the etiologic agents of proventricular dilatation disease (PDD), a frequently fatal neurologic disease of captive parrots. Seven ABV genogroups have been identified worldwide from a variety of sources, and that number may increase as surveillance for novel Bornaviruses continues. Here, we report the first complete sequence of a genogroup 1 avian Bornavirus (ABV1).
Michael Lierz - One of the best experts on this subject based on the ideXlab platform.
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age dependent development and clinical characteristics of an experimental parrot Bornavirus 4 pabv 4 infection in cockatiels nymphicus hollandicus
Avian Pathology, 2021Co-Authors: Anna Maria Gartner, Sibylle Herzog, Dirk Enderlein, Christiane Herden, Sara Malberg, Jessica Link, Bianca Bucking, J Petzold, Michael LierzAbstract:Parrot Bornavirus (PaBV) is a pathogen often found in psittacine populations. Infected, clinically healthy carrier birds are of major importance for epidemiology, but the underlying pathomechanism ...
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Avian Bornavirus in free-ranging psittacine birds, Brazil.
Emerging infectious diseases, 2014Co-Authors: Nuri Encinas-nagel, U. Heffels-redmann, Anne Piepenbring, Dirk Enderlein, Christiane Herden, Paulo A.n. Felippe, Clarice Weis Arns, Hafez M. Hafez, Michael LierzAbstract:Avian Bornavirus (ABV) has been identified as the cause of proventricular dilatation disease in birds, but the virus is also found in healthy birds. Most studies of ABV have focused on captive birds. We investigated 86 free-ranging psittacine birds in Brazil and found evidence for natural, long-term ABV infection.
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Pathogenesis of Avian Bornavirus in Experimentally Infected Cockatiels
Emerging infectious diseases, 2012Co-Authors: Anne Piepenbring, U. Heffels-redmann, Sibylle Herzog, Erhard F. Kaleta, Dirk Enderlein, Christiane Herden, Saskia Ressmeyer, Michael LierzAbstract:Avian Bornavirus (ABV) is the presumed causative agent of proventricular dilatation disease (PDD), a major fatal disease in psittacines. However, the influencing factors and pathogenesis of PDD are not known and natural ABV infection exhibits remarkable variability. We investigated the course of infection in 18 cockatiels that were intracerebrally and intravenously inoculated with ABV. A persistent ABV infection developed in all 18 cockatiels, but, as in natural infection, clinical disease patterns varied. Over 33 weeks, we simultaneously studied seroconversion, presence of viral RNA and antigens, infectious virus, histopathologic alterations, and clinical signs of infection in the ABV-infected birds. Our study results further confirm the etiologic role of ABV in the development of PDD, and they provide basis for further investigations of the pathogenetic mechanisms and disease-inducing factors for the development of PDD.
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Vertical transmission of avian Bornavirus in psittacines.
Emerging infectious diseases, 2011Co-Authors: Michael Lierz, U. Heffels-redmann, Anne Piepenbring, Christiane Herden, Kirstin Oberhauser, Dirk EnderleinAbstract:To the Editor: Proventricular dilatation disease (PDD) is a fatal disease in psittacines that jeopardizes critical species conservation projects, such as that involving the Spix’s macaw (Cyanopsitta spixii), the world’s most endangered bird species (1). The disease is characterized by lymphoplasmacytic infiltrations in the enteric and central nervous systems (2). Consequently, gastrointestinal and neurologic disorders are the major clinical manifestations. Only recently has the cause of the disease been identified by characterization of a newly discovered member of the family Bornaviridae, the avian Bornavirus (ABV), which has been detected in affected psittacines (3,4). The relationship of an infection with ABV and the occurrence of PDD has been described in natural cases (5,6) and in experimental trials (7,8). However, birds that are infected with ABV but that are clinically healthy have also been recognized (6). Infected birds can shed viral RNA intermittently (9), and not all infected birds seroconvert (5). For psittacine flock management, control of an AΒV infection is critical, e.g., by repeated testing of breeding stock and removal of ABV-positive birds (2,5). However, in breeding projects of rare species, every individual is genetically important and cannot be lost. Therefore, pairing infected, but clinically healthy, birds separately from birds that test negative for the virus might represent an option. For this possibility to be viable, whether vertical transmission of ABV can take place must be further clarified. A study investigating the distribution of ABV in tissues of PDD-positive birds has demonstrated ABV antigen in follicular cells, which may point toward vertical transmission (9). To investigate vertical transmission of ABV, we examined 30 dead-in-shell embryos of various psittacine species that originated from ABV-infected flocks with a history of PDD. First, the eggshell was disinfected and opened at the blunt end by using sterile equipment. The brain and proventriculus of each embryo were analyzed for the presence of ABV RNA by using 2 different real-time reverse transcription PCRs, as described by Honkavuori (4), with the primer pair 1034–1322 and, in case of a negative result, the additional primer set 1367. Sampling, RNA extraction, and PCR were repeated by using the same methods to exclude possible cross-contamination of samples. Afterwards, the complete embryo was placed in 10% buffered formalin, and histopathologic examination and immunohistochemical (IHC) testing were carried out (10) with antibodies directed against the viral phosphoprotein and X protein. If ABV RNA or ABV antigen was demonstrated, crop and cloacal swab specimens and serum of the parents of the positive embryo were immediately taken and used either for ABV RNA detection with the above described PCR or for the detection of specific ABV antibodies by indirect immunofluorescence assay (10). This procedure was chosen because earlier sampling of the parents might have caused breeding interruption, and which eggs of which parents would be available for investigation was not clear. In 2 of the 30 embryos investigated, ABV RNA was detected by using the 1034 PCR. The repeated procedure provided the same results in the same embryos. One embryo was a Major Mitchell cockatoo (Cacatua leadbeateri) (cycle threshold 31.41) and the other a red-crowned Amazon (Amazona viridigenalis) (cycle threshold 35.1). None of the investigated embryos demonstrated histopathologic lesions typical of an ABVinfection. IHC testing did not show any positive results. However, in the ABV-positive Amazon embryo, an equivocal result was obtained. The swab specimens of both parents of the Major Mitchell cockatoo tested positive for ABV RNA, but serum did not demonstrate specific ABV antibodies. The crop swab specimen of the female red crowned Amazon was positive for ABV RNA, but serum was negative for ABV antibodies; the male bird tested negative by PCR but demonstrated an ABV-specific antibody titer of 80. These results highlight the potential risk for vertical transmission of ABV and the conclusion that ABV-infected parents can most likely produce infected offspring. However, test results were positive for only 2 of 30 eggs. Because potentially dead-in-shell embryos are usually further incubated by the breeder to ensure embryonic death, the possibility cannot be excluded that ABV RNA was already degraded in some cases, thus causing false-negative results. On the other hand, these eggs might have originated from ABV-negative parents. The quality of the samples might also have caused the questionable IHC results. In PDD-affected, ABV-positive flocks >30% of the birds could be infected (5,6) and the virus is shed intermittently (9). Therefore, pairing ABV-positive birds, incubating their eggs artificially, and raising the chicks separately until they show negative test results, might be an option for breeding projects. However, when vertical transmission occurs (and, if so, its incidence) is unknown. Whether ABV infection of the embryos was the cause of death remains unclear. Even if typical lesions were not detected, the poor quality of the material might have hidden such lesions. However, embryonic infection that does not result in embryonic death is the basic requirement for successful vertical transmission. These preliminary results warrant further studies investigating the possibility of vertical transmission by ABV-infected pairs, especially to minimize the risk for such transmission to endangered species with restricted breeding opportunities.
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Indirect Immunofluorescence Assay for Intra Vitam Diagnosis of Avian Bornavirus Infection in Psittacine Birds
Journal of clinical microbiology, 2010Co-Authors: Sibylle Herzog, U. Heffels-redmann, Anne Piepenbring, Erhard F. Kaleta, Dirk Enderlein, Hermann J Muller, Michael Lierz, D. Neumann, Christiane HerdenAbstract:Different avian Bornavirus (ABV) genotypes have recently been detected in psittacine birds with proventricular dilatation disease (PDD), an inflammatory fatal central and peripheral nervous system disorder. An indirect immunofluorescence assay (IIFA) for intra vitam demonstration of ABV-specific serum antibodies was established since reverse transcription-PCR (RT-PCR) assays may not detect all ABV variants.
