Reverse genetics of parrot bornavirus 4 reveals a unique splicing of the glycoprotein gene that affects viral propagation.

Viruses can utilize host splicing machinery to enable the expression of multiple genes from a limited-sized genome. Orthobornaviruses use alternative splicing to regulate the expression level of viral proteins and achieve efficient viral replication in the nucleus. Although more than 20 orthobornaviruses have been identified belonging to eight different viral species, virus-specific splicing has not been demonstrated. Here, we demonstrate that the glycoprotein (G) transcript of parrot bornavirus 4 (PaBV-4; species Orthobornavirus alphapsittaciforme), a highly virulent virus in psittacines, undergoes mRNA splicing and expresses a soluble isoform termed sGP. Interestingly, the splicing donor for sGP is not conserved in other orthobornaviruses, including those belonging to the same orthobornavirus species, suggesting that this splicing has evolved as a PaBV-4-specific event. We have also shown that exogenous expression of sGP does not affect PaBV-4 replication or de novo virion infectivity. In this study, to investigate the role of sGP in viral replication, we established a reverse genetics system for PaBV-4 by using avian cell lines and generated a recombinant virus lacking the spliced mRNA for sGP. Using the recombinant viruses, we show that the replication of the sGP-deficient virus is significantly slower than that of the wild-type virus and that the exogenous expression of sGP cannot restore its propagation efficiency. These results suggest that autologous or controlled expression of sGP by splicing may be important for PaBV-4 propagation. The reverse genetics system for avian bornaviruses developed here will be a powerful tool for understanding the replication strategies and pathogenesis of avian orthobornaviruses. IMPORTANCE Parrot bornavirus 4 (PaBV-4) is the dominant cause of proventricular dilatation disease, a severe gastrointestinal and central nervous system disease among avian bornaviruses. In this study, we discovered that PaBV-4 expresses a soluble isoform of glycoprotein (G), called sGP, through alternative splicing of the G mRNA, which is unique to this virus. To understand the role of sGP in viral replication, we generated recombinant PaBV-4 lacking the newly identified splicing donor site for sGP using a reverse genetics system and found that its propagation was significantly slower than that of the wild-type virus, suggesting that sGP plays an essential role in PaBV-4 infection. Our results provide important insights not only into the replication strategy but also into the pathogenesis of PaBV-4, which is the most prevalent bornavirus in captive psittacines worldwide.

Bornavirus Encephalitis Shows a Characteristic Magnetic Resonance Phenotype in Humans.

OBJECTIVE: The number of diagnosed fatal encephalitis cases in humans caused by the classical Borna disease virus (BoDV-1) has been increasing, ever since it was proved that BoDV-1 can cause human infections. However, awareness of this entity is low, and a specific imaging pattern has not yet been identified. We therefore provide the first comprehensive description of the morphology of human BoDV-1 encephalitis, with histopathological verification of imaging abnormalities. METHODS: In an institutional review board-approved multicenter study, we carried out a retrospective analysis of 55 magnetic resonance imaging (MRI) examinations of 19 patients with confirmed BoDV-1 encephalitis. Fifty brain regions were analyzed systematically (T1w, T2w, T2*w, T1w + Gd, and DWI), in order to discern a specific pattern of inflammation. Histopathological analysis of 25 locations in one patient served as correlation for MRI abnormalities. RESULTS: Baseline imaging, acquired at a mean of 11 ± 10 days after symptom onset, in addition to follow-up scans of 16 patients, revealed characteristic T2 hyperintensities with a predilection for the head of the caudate nucleus, insula, and cortical spread to the limbic system, whereas the occipital lobes and cerebellar hemispheres were unaffected. This gradient was confirmed by histology. Nine patients (47.4%) developed T1 hyperintensities of the basal ganglia, corresponding to accumulated lipid phagocytes on histology and typical for late-stage necrosis. INTERPRETATION: BoDV-1 encephalitis shows a distinct pattern of inflammation in both the early and late stages of the disease. Its appearance can mimic sporadic Creutzfeldt-Jakob disease on MRI and should be considered a differential diagnosis in the case of atypical clinical presentation. ANN NEUROL 2020;88:723-735.

Distribution of Viral Antigen and Inflammatory Lesions in the Central Nervous System of Cockatiels ( Nymphicus hollandicus) Experimentally Infected with Parrot Bornavirus 2.

Neurotropism is a striking characteristic of bornaviruses, including parrot bornavirus 2 (PaBV-2). Our study evaluated the distribution of inflammatory foci and viral nucleoprotein (N) antigen in the brain and spinal cord of 27 cockatiels ( Nymphicus hollandicus) following experimental infection with PaBV-2 by injection into the pectoral muscle. Tissue samples were taken at 12 timepoints between 5 and 114 days post-inoculation (dpi). Each experimental group had approximately 3 cockatiels per group and usually 1 negative control. Immunolabeling was first observed within the ventral horns of the thoracic spinal cord at 20 dpi and in the brain (thalamic nuclei and hindbrain) at 25 dpi. Both inflammation and viral antigen were restricted to the central core of the brain until 40 dpi. The virus then spread quickly at 60 dpi to both gray and white matter of all analyzed sections of the central nervous system (CNS). Encephalitis was most severe in the thalamus and hindbrain, while myelitis was most prominent in the gray matter and equally distributed in the cervical, thoracic, and lumbosacral spinal cord. Our results demonstrate a caudal to rostral spread of virus in the CNS following experimental inoculation of PABV-2 into the pectoral muscle, with the presence of viral antigen and inflammatory lesions first in the spinal cord and progressing to the brain.

Analysis of exotic squirrel trade and detection of human infections with variegated squirrel bornavirus 1, Germany, 2005 to 2018.

Following the discovery in 2015 of the variegated squirrel bornavirus 1 (VSBV-1) in fatal encephalitis cases among exotic squirrel breeders and a zoo animal caretaker in Germany, a case definition was developed. It was employed during trace-back animal trade investigations and sero-epidemiological studies among breeders and zoo animal caretakers of holdings with VSBV-1 infected squirrels. During the investigation, two possible human cases who had died of encephalitis were identified retrospectively among the squirrel breeders. Moreover, one probable human case was detected among the breeders who had a positive memory T-cell response to VSBV-1 antigen and antibodies against VSBV-1. The low rate of seropositivity found among living persons in risk groups that handle exotic squirrels privately or at zoos may reflect rareness of exposure to VSBV-1 during animal contact, a high lethality of infection or a combination of these factors. As a precaution against human exposure, testing of exotic squirrels for VSBV-1 infection and/or avoiding direct contact with exotic squirrels in zoos and private holdings is strongly advised.

A Variegated Squirrel Bornavirus Associated with Fatal Human Encephalitis.

Between 2011 and 2013, three breeders of variegated squirrels (Sciurus variegatoides) had encephalitis with similar clinical signs and died 2 to 4 months after onset of the clinical symptoms. With the use of a metagenomic approach that incorporated next-generation sequencing and real-time reverse-transcriptase quantitative polymerase chain reaction (RT-qPCR), the presence of a previously unknown bornavirus was detected in a contact squirrel and in brain samples from the three patients. Phylogenetic analyses showed that this virus, tentatively named variegated squirrel 1 bornavirus (VSBV-1), forms a lineage separate from that of the known bornavirus species. (Funded by the Federal Ministry of Food and Agriculture [Germany] and others.).

Fatal proventricular dilatation disease in captive native psittacines in Brazil.

An outbreak of proventricular dilatation disease (PDD), a fatal inflammatory disease of psittacines (Aves: Psittaciformes), is described in native Brazilian psittacines. Twenty captive psittacines that died of suspected PDD were necropsied and 10 were submitted to histopathology, reverse transcriptase PCR (RT-PCR), and immunohistochemistry (IHC) for avian bornavirus (ABV). Examined species were one pileated parrot (Pionopsitta pileata), three vinaceous-breasted parrots (Amazona vinacea), two blue-winged macaws (Primolius maracana), one scarlet macaw (Ara macao), one chestnut-fronted macaw (Ara severa), one scaly-headed parrot (Pionus maximiliani), and one red-browed Amazon parrot (Amazona rhodocorytha). Gross examination and histopathology revealed typical PDD lesions in all birds. The presence of ABV was confirmed in four psittacines including one red-browed Amazon parrot, one blue-winged macaw, one scarlet macaw, and one chestnut-fronted macaw. In the red-browed Amazon parrot and in one blue-winged macaw, IHC demonstrated ABV antigens in the nucleus and cytoplasm of cells in various organs. This is the first description of PDD by ABV in Brazilian psittacines and indicates the necessity for adopting a strategic control plan for reducing its impact in native birds.

Genetic trends in parrot Bornavirus: a clinical analysis.

Parrot Bornavirus (PaBV) has been reported to cause indigestion and other wasting symptoms such as weight loss and lethargy. The pathogenesis of PaBV has yet to be fully elucidated. This study reports PaBV infections in South Korea and suggests a trend in the genetic information gathered from clinical cases. A total of 487 birds with or without clinical symptoms were tested for bornavirus. Twelve of 361 asymptomatic birds tested positive for bornavirus, while 15 of 126 birds with various symptoms tested positive. A segment of approximately 1,540 bps including the N, X, P and M proteins were obtained from 23 of the positive strains and analyzed with other strains found on GenBank that had clinical information. PaBV was type 2 and 4 in South Korea, and certain amino acid sequences showed a difference between symptom presenting animals and asymptomatic animals in the X protein and P protein. When considering that some asymptomatic cases may have been latent infections at the time of examination, it is plausible these trends may grow stronger with time. Majority of PaBV was type 4 in South Korea. If these trends are confirmed, diagnosis of potentially pathogenic PaBVs in a clinical manner will be possible during the early stages of infection.

Betanodavirus meningoencephalitis in an Atlantic blue marlin.

Viral nervous necrosis (viral encephalopathy and retinopathy) is caused by piscine nodavirus (Nodaviridae, Betanodavirus). Since 1986, this highly infectious virus has caused mass mortalities of up to 100% in farmed saltwater and freshwater fish around the world (with the exception of South America and Antarctica), affecting >60 species across 10 orders. The Atlantic blue marlin (Makaira nigricans Lacépède, 1802) is a top-level predator found throughout the tropical waters of the Atlantic and Indo-Pacific oceans. Despite their popularity as a sportfish, relatively little is known about the Atlantic blue marlin and other billfish. We describe here chronic betanodavirus infection in a juvenile Atlantic blue marlin, which is, to our knowledge, the first report of disease in M. nigricans.

Pathology and diagnosis of avian bornavirus infection in wild Canada geese (Branta canadensis), trumpeter swans (Cygnus buccinator) and mute swans (Cygnus olor) in Canada: a retrospective study.

Nine hundred and fifty-five pathology cases collected in Ontario between 1992 and 2011 from wild free-ranging Canada geese, trumpeter swans and mute swans were retrospectively evaluated for the pathology associated with avian bornavirus (ABV) infection. Cases were selected based on the presence of upper gastrointestinal impaction, central nervous system histopathology or clinical history suggestive of ABV infection. The proportion of birds meeting at least one of these criteria was significantly higher at the Toronto Zoo (30/132) than elsewhere in Ontario (21/823). Central, peripheral and autonomic nervous tissues were examined for the presence of lymphocytes and plasma cells on histopathology. The presence of virus was assessed by immunohistochemistry and reverse transcriptase-polymerase chain reaction (RT-PCR) on frozen brains and on formalin-fixed paraffin-embedded tissues. Among selected cases, 86.3% (44/51) were considered positive on histopathology, 56.8% (29/51) were positive by immunohistochemistry, and RT-PCR was positive on 88.2% (15/17) of the frozen brains and 78.4% (40/51) of the formalin-fixed paraffin-embedded samples. Histopathological lesions included gliosis and lymphoplasmacytic perivascular cuffing in brain (97.7%), spinal cord (50%), peripheral nerves (55.5%) and myenteric ganglia or nerves (62.8%), resembling lesions described in parrots affected with proventricular dilatation disease. Partial amino acid sequences of the nucleocapsid gene from seven geese were 100% identical amongst themselves and 98.1 to 100% identical to the waterfowl sequences recently described in the USA. Although ABV has been identified in apparently healthy geese, our study confirmed that ABV can also be associated with significant disease in wild waterfowl species.

Follow-up investigations on different courses of natural avian bornavirus infections in psittacines.

To study the course of natural avian bornavirus (ABV) infection, 63 psittacines of three bird collections where ABV had been demonstrated were investigated over a period of 1 yr. The psittacines were clinically observed and swabs of crop and cloaca as well as serum samples were collected three separate times at intervals of 2-6 mo. According to the results of detection of ABV RNA by reverse transcriptase polymerase chain reaction (RT-PCR) and of anti-ABV antibodies by indirect immunofluorescence assay (IIFA), 43 of the birds were found to be infected with ABV. Based on variations in virus shedding and antibody production in combination with the occurrence of proventricular dilatation disease (PDD) -related clinical signs, pathological findings, and lethal outcome, four different groups of infected psittacines and a fifth group of noninfected psittacines were identified. Group 1 comprised six birds with various courses of ABV infection and forms of clinical PDD. Groups 2-4 included all birds with subclinical ABV infections: Group 2 contained 13 birds that were consistently (subgroup A, 6 birds) or inconsistently (subgroup B, 7 birds) ABV positive by PCR and serology; group 3 was composed of 13 psittacines exhibiting only anti-ABV antibodies; and 8 birds that had positive ABV RNA detection in crop and cloaca, but did not develop anti-ABV specific antibodies, were classified in group 4. Twenty-three out of the 63 psittacines remained free of detectable ABV RNA or anti-ABV antibodies over the whole observation period (group 5). Based on the results, it seems that birds with high ABV RNA load in crop and cloaca combined with high anti-ABV antibodies have a high risk of the development of PDD, indicating that the humoral antibodies do not protect against the disease. The meaning of the detection of ABV RNA and antibodies at a low and inconsistent level for the single bird as well as for the epidemiology of the ABV infection remained unclear in this field study and needs to be further investigated.

Vasculitis Associated with Parrot Bornavirus 4 Infection in a Rose-Crowned Parakeet (Pyrrhurarhodocephala).

A 3-month-old, female rose-crowned parakeet (Pyrrhura rhodocephala) was found dead after a 24-h course of lethargy and passing blood-tinged faeces. Fine white streaks were seen in the pectoral muscles on necropsy. Microscopic examination revealed typical lesions of avian ganglioneuritis and vascular necrosis in the pectoral muscles, myocardium, kidneys, air sacs, adrenal glands, pancreas and thyroid gland. These lesions were characterized by mural fibrinoid necrosis of small and medium-calibre arteries and arterioles, associated with lymphoplasmacytic inflammation, necrosis, atrophy and fibrosis of the surrounding tissues. Parrot bornavirus (PaBV) nucleoprotein was demonstrated by immunohistochemistry in smooth muscle and endothelial cells of many vessels. An avian bornavirus was isolated from kidney tissue and its identity confirmed as PaBV-4 by sequencing and phylogenetic analysis. We postulate that the vascular lesions could have been immune-mediated and that PaBV-4 may have played a role in its pathogenesis.

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.

Proventricular dilatation disease in cockatiels (Nymphicus hollandicus) after infection with a genotype 2 avian bornavirus.

An isolate of genotype 2 avian bornavirus (ABV) was recovered from a cockatiel (Nymphicus hollandicus) that was euthanatized for an unrelated lesion and showing no clinical evidence of proventricular dilatation disease (PDD). On histopathologic examination, mild inflammatory lesions were present in the heart and brain, but gastrointestinal lesions characteristic of classic PDD were not observed. To investigate if this ABV2 isolate had reduced virulence, the virus was propagated in duck embryo fibroblasts and inoculated into 2 adult cockatiels by the oral and intramuscular routes. One bird developed clinical signs on day 33 and was euthanatized on day 36. The second challenged bird developed clinical signs on day 41 and was euthanatized on day 45. At necropsy, the proventriculus of both birds was slightly enlarged. Histopathologic examination showed lesions typical of PDD in the brain, spinal cord, heart, adrenal gland, and intestine. A control, uninoculated cockatiel was apparently healthy when euthanatized on day 50. These results show that ABV2 is now the second ABV genotype to be formally shown to cause PDD.

Indirect immunofluorescence assay for intra vitam diagnosis of avian bornavirus infection in psittacine birds.

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.

Broad tissue and cell tropism of avian bornavirus in parrots with proventricular dilatation disease.

Avian bornaviruses (ABV), representing a new genus within the family Bornaviridae, were recently discovered in parrots from North America and Israel with proventricular dilatation disease (PDD). We show here that closely related viruses are also present in captive European parrots of various species with PDD. The six ABV strains that we identified in clinically diseased birds are new members of the previously defined ABV genotypes 2 and 4. Viruses of both genotypes readily established persistent, noncytolytic infections in quail and chicken cell lines but did not grow in cultured mammalian cells in which classical Borna disease virus strains replicate very efficiently. ABV antigens were present in both the cytoplasm and nucleus of infected cells, suggesting nuclear replication of ABV. The genome organization of avian and mammalian bornaviruses is highly conserved except that ABV lacks a distinct control element in the 5' noncoding region of the bicistronic mRNA encoding the viral proteins X and P. Reverse transcription-PCR analysis demonstrated the presence of virus in many, if not all, organs of birds with PDD. Viral nucleic acid was also found in feces of diseased birds, suggesting virus transmission by the fecal-oronasal route. Immunohistochemical analysis of organs from birds with PDD revealed that infection with ABV is not restricted to cells of the nervous system. Thus, ABV exhibits a broad tissue and cell tropism that is strikingly different from classical Borna disease virus.

Update on Avian Bornavirus and Proventricular Dilatation Disease: Diagnostics, Pathology, Prevalence, and Control.

Avian bornavirus (ABV) is a neurotropic virus that can cause gastrointestinal and/or neurologic signs of disease in birds. The disease process is called proventricular dilatation disease (PDD). The characteristic lesions observed in birds include encephalitis and gross dilatation of the proventriculus. ABV is widely distributed in captive and wild bird populations. Most birds infected do not show clinical signs of disease. This article is an update of the Veterinary Clinics of North America article from 2013: Avian Bornavirus and Proventricular Dilatation Disease: Diagnostics, Pathology, Prevalence, and Control.

Cardiac Lesions of Natural and Experimental Infection by Parrot Bornaviruses.

Lymphoplasmacytic inflammation associated with bornavirus N protein occurs in the epicardial ganglia, myocardium and endocardium of birds diagnosed with proventricular dilatation disease (PDD). These pathological findings suggest that sudden death in psittacine birds might stem from cardiac compromise due to parrot bornavirus (PaBV) infection. Therefore, we investigated cardiac lesions in cases of PDD, searching databases from 1988 to 2019, and reviewed three experimental studies of PaBV infection. Fifty cases of PDD in birds infected naturally with PaBV and 27 cases of PDD in birds infected experimentally with PaBV (all having descriptions of inflammatory cardiac lesions) were reviewed. For each case, five regions of the heart were evaluated by light microscopy and immunohistochemistry (IHC). These regions were the epicardial ganglia/nerves, the endocardium, the myocardium, the Purkinje fibres and the great vessels. Sudden death was documented in 17/50 naturally infected cases, while 23/50 had digestive signs, and only 12/50 had neurological signs. Grossly, only five naturally-infected and five experimentally-infected cases had cardiomegaly or hydropericardium. Epicardial ganglioneuritis was the most consistent microscopical finding in natural (46/50) and experimental cases (26/27), followed by myocarditis (34/50) for naturally-infected and endocarditis for experimentally-infected birds (6/27). PaBV-2 antigen was detected most frequently by IHC in the epicardial ganglia (54/77) compared with the other tissues. This retrospective study demonstrates the presence of PaBV protein and inflammation in the heart of birds infected with PaBV and suggests a link between PaBV and cardiac disease and sudden death in psittacine birds.

Parrot bornavirus in naturally infected Brazilian captive parrots: Challenges in viral spread control.

Psittaciform orthobornaviruses are currently considered to be a major threat to the psittacine bird population worldwide. Parrot bornavirus (PaBV) was identified recently in Brazil and, since then, few studies have been conducted to understand the epidemiology of PaBV in captive psittacine birds. In the present study, natural infections by PaBV in South American parrots were investigated in two breeding facilities: commercial (A) and conservationist (B). Thirty-eight psittacine of 21 different species were presented for postmortem examination. Tissue samples were collected and investigated for the presence of PaBV-RNA using RT-PCR. In addition, clinical information about these birds was used when available. PaBV infection was detected in 73.7% of all birds investigated, indicating a wide dissemination of this virus in both facilities. From birds investigated in aviary A, 66.7% showed clinical signs, 100% had typical lesions of proventricular dilatation disease (PDD), 100% had mild to severe proventricular dilatation and 88.9% were PaBV-positive. In birds from aviary B, 27.6% showed clinical signs, 65.5% had typical lesions of PDD, 62% had mild to severe proventricular dilatation and 69% were PaBV-positive. Neurological disease was observed more frequently than gastrointestinal disease. Sequencing analysis of the matrix gene fragment revealed the occurrence of genotype 4 (PaBV-4) in both places. About 15.8% of birds in this study are threatened species. We discussed the difficulties and challenges for controlling viral spread in these aviaries and implications for South American psittacine conservation. These results emphasize the urgent need to develop a national regulatory and health standard for breeding psittacine birds in the country.

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

BACKGROUND: Proventricular 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). RESULTS: Five 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. CONCLUSION: In 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.

Avian Ganglioneuritis in Clinical Practice.

Avian ganglioneuritis (AG) comprises one of the most intricate pathologies in avian medicine and is researched worldwide. Avian bornavirus (ABV) has been shown to be a causative agent of proventricular dilatation disease in birds. The avian Bornaviridae represent a genetically diverse group of viruses that are widely distributed in captive and wild populations around the world. ABV and other infective agents are implicated as a cause of the autoimmune pathology that leads to AG, similar to human Guillain Barrè syndrome. Management of affected birds is beneficial and currently centered at reducing neurologic inflammation, managing secondary complications, and providing nutritional support.