Avian Bornavirus Research Articles

Detection of Avian Bornavirus in Parrots with Proventricular Dilation Disease (Pdd) by In-Situ Hybridization

Detection of Avian Bornavirus in Parrots with Proventricular Dilation Disease (Pdd) by In-Situ Hybridization

Histopathology and the detection of avian bornavirus in the nervous system of birds diagnosed with proventricular dilatation disease

Avian bornavirus (ABV) is currently considered a probable etiologic agent of proventricular dilatation disease (PDD) of psittacines. We tested 24 stored avian brain samples, processed for histopathology and retained following their submission for necropsy or histopathology to the Schubot Exotic Bird Center diagnostic laboratory in 1992. Thirteen of these samples were from birds diagnosed at that time as suffering from PDD. The remaining 11 samples were diagnosed as suffering from diseases other than PDD. Immunohistochemistry was performed using an antiserum directed against the ABV nucleoprotein (N-protein). Stained slides were read by an investigator unaware of their prior histopathology results. Cells containing ABV N-protein were present in the nervous tissues of all 13 PDD cases. One bird not previously diagnosed with PDD also had ABV N-protein in its brain. A review of this bird's necropsy report indicated that it was, most probably, also suffering from PDD. The remaining 10 non-PDD birds had no detectable N-protein in their brains. The N-protein was present in the cerebrum, cerebellum and spinal cord. These findings support other studies that indicate that ABV is an etiological agent of PDD.

Avian Bornaviruses in Psittacine Birds from Europe and Australia with Proventricular Dilatation Disease

To determine whether avian bornaviruses (ABVs) were a factor in proventricular dilatation disease (PDD), we used immunohistochemistry, reverse transcription-PCR, and nucleotide sequence analysis to examine paraffin wax-embedded or frozen tissue samples of 31 psittacine birds with this disease. PDD is a fatal disease of psittacine birds associated with nonsuppurative encephalitis and ganglioneuritis of the upper intestinal tract. Tissue samples had been collected from 1999 through 2008 in Austria, Switzerland, Hungary, and Australia. Immunohistochemical demonstration of viral antigen within the brain and vegetative nerve system of the gastrointestinal tract provides strong evidence for a causative role of ABVs in this condition. Partial sequences of nucleoprotein (p40) and matrix protein (gp18) genes showed that virus in most of our cases belonged to the ABV-2 and ABV-4 groups among the 5 genogroups described so far. Viral sequences of 2 birds did not match any of the described sequences and clustered together in a new branch termed ABV-6.

Novel Avian Bornavirus in a Nonpsittacine Species (Canary; Serinus canaria ) with Enteric Ganglioneuritis and Encephalitis

A canary bird (Serinus canaria) died with nonsuppurative ganglioneuritis of the proventriculus and gizzard and encephalitis, lesions comparable to proventricular dilatation disease (PDD) of psittacine birds. Recently, several genotypes of a novel avian bornavirus have been linked to PDD. In the canary, bornaviral antigen was detected by immunohistochemistry in both neural and extraneural tissues. The widespread viral dissemination was confirmed by reverse transcription-PCR. Sequence analysis revealed a unique genotype of avian bornavirus. This observation suggests that bornaviruses are natural pathogens of several avian species and that the family Bornaviridae comprises more viral genotypes (or viral species) than previously assumed.

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.

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.

Recovery of divergent avian bornaviruses from cases of proventricular dilatation disease: Identification of a candidate etiologic agent

BackgroundProventricular dilatation disease (PDD) is a fatal disorder threatening domesticated and wild psittacine birds worldwide. It is characterized by lymphoplasmacytic infiltration of the ganglia of the central and peripheral nervous system, leading to central nervous system disorders as well as disordered enteric motility and associated wasting. For almost 40 years, a viral etiology for PDD has been suspected, but to date no candidate etiologic agent has been reproducibly linked to the disease.ResultsAnalysis of 2 PDD case-control series collected independently on different continents using a pan-viral microarray revealed a bornavirus hybridization signature in 62.5% of the PDD cases (5/8) and none of the controls (0/8). Ultra high throughput sequencing was utilized to recover the complete viral genome sequence from one of the virus-positive PDD cases. This revealed a bornavirus-like genome organization for this agent with a high degree of sequence divergence from all prior bornavirus isolates. We propose the name avian bornavirus (ABV) for this agent. Further specific ABV PCR analysis of an additional set of independently collected PDD cases and controls yielded a significant difference in ABV detection rate among PDD cases (71%, n = 7) compared to controls (0%, n = 14) (P = 0.01; Fisher's Exact Test). Partial sequence analysis of a total of 16 ABV isolates we have now recovered from these and an additional set of cases reveals at least 5 distinct ABV genetic subgroups.ConclusionThese studies clearly demonstrate the existence of an avian reservoir of remarkably diverse bornaviruses and provide a compelling candidate in the search for an etiologic agent of PDD.

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.