Proventricular dilatation disease (PDD) is a progressive, invariably fatal neurologic disease that has been reported for >50 species of psittacine birds as well as many other bird species (1
). It is considered a serious disease because many of these birds are highly endangered, and several affected species depend on captive breeding for their survival. The clinical signs of PDD vary and may be predominately neurologic (weakness, ataxia, proprioceptive deficits, seizures, blindness), gastrointestinal (weight loss, passage of undigested food, regurgitation, delayed crop emptying), or a combination thereof (2
). The gastrointestinal signs, especially proventricular dilatation, are secondary to pseudo-obstruction brought about by damage to the enteric nervous system. PDD is characterized by severe lymphoplasmacytic inflammation in peripheral, central, and autonomic nervous tissues (3
). Definitive diagnosis of PDD requires demonstration of lymphoplasmacytic ganglioneuritis in the intestinal tract.
Recently, 2 independent groups of investigators identified a new member of the family Bornaviridae
, named avian bornavirus (ABV), in parrots with histopathologically confirmed PDD. Honkavuori et al. used unbiased high-throughput sequencing to identify the virus in several parrots with histopathologically confirmed PDD (6
). Quantitative PCR confirmed the presence of the virus in brain, proventriculus, and adrenal gland in 3 birds with PDD but not in 4 unaffected birds. Kistler (7
) used a panviral microarray to identify a bornavirus hybridization signature in 5 of 8 birds with PDD and 0 of 8 controls. These investigators used ultra high-throughput sequencing combined with conventional PCR-based cloning to recover a complete viral genome sequence. Before this discovery, the family Bornaviridae
contained only 1 species, Borna disease virus
(BDV). BDV causes a neurologic syndrome, Borna disease, which is restricted to central Europe, where it is found primarily in horses and sheep. The virus infects neurons and astrocytes, and the resulting disease appears to be mediated by an immunopathologic response of the host to the virus.
BDV can be grown in mammalian cell culture, where it causes a noncytolytic persistent infection. Borna disease appears as a sporadic infection affecting small numbers of animals each year. Its epidemiology is unclear, but it may be carried by certain species of shrews (8
). BDV has also been detected in the feces of wild birds and in captive ostriches, but the epidemiologic significance of this observation is unclear (9
). Studies undertaken in this laboratory have demonstrated some histopathologic similarities, in particular in the selective destruction of cerebellar Purkinje cells, between ABV and BDV infections of the brains of birds and mammals, respectively (11
Seven ABV genotypes have been identified based on partial genome sequencing (12
). In general, these ABV strains show only ≈65% sequence identity with BDV. Nevertheless, the overall structure of the bornaviral genome is well conserved (6
). Thus, the number and order of genes is unchanged, as is the structure of transcription initiation and termination sites. Recently, Rinder et al. (14
) have shown that the region between the N and X gene in ABV is shorter than that in BDV. ABV apparently lacks a 22-nt fragment that serves a regulatory function for the genes coding for viral proteins X and P.
Although these discoveries suggest that ABV is a plausible cause of PDD, as described in Koch’s postulates, proof of a causal relationship requires isolation of the agent from infected birds; its propagation in culture; and, after reintroduction of the isolate into a susceptible host, manifestation of the disease (15
). We describe the isolation and culture of ABV from the brains of 8 psittacine birds with histopathologically confirmed PDD. After 6 passages, 1 of the cultured isolates was intramuscularly injected into 2 healthy Patagonian conures (Cyanoliseus patagonis
). Typical PDD subsequently developed in each bird, and the inoculated virus was found in the brain.