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

Amy L Kistler,Susan Clubb,Ady Gancz,Yigal Farnoushi,Alexander Greninger,Charles Y Chiu,Kael Fischer,Scott B Karlene,Peter Skewes-Cox,Christopher C Wen,Sara Mechani,Joseph L Derisi,Avishai Lublin,Don Ganem,Katherine Sorber

doi:10.1186/1743-422x-5-88

Abstract

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.

Highlights

Proventricular dilatation disease (PDD) is a fatal disorder threatening domesticated and wild psittacine birds worldwide
(page number not for citation purposes) http://www.virologyj.com/content/5/1/88 samples originating in the United States, consisted of crop biopsy specimens from 3 histologically confirmed PDD cases and 5 controls that were provided for nucleic acid extraction and follow-up Virus chip analysis
Host filter were screened for the presence of bornavirus sequence through similar ELAND and iterative BLAST analyses (Materials and Methods) using a database generated from all Borna Disease virus (BDV) sequences present in NCBI (n = 207) and the sequences we had recovered from PCR follow-up of the PDD samples that tested positive for bornavirus by Virus chip microarray (n = 5)

Summary

Introduction

Proventricular 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. Proventricular dilatation disease (PDD) is considered by many to be the greatest threat to aviculture of psittacine birds (parrots). If not all major psittacine collections throughout the world have experienced cases of PDD It has been devastating in countries like Canada and northern areas of the United States where parrots are housed primarily indoors. Captive breeding efforts for at least one psittacine which is thought to be extinct in the wild, the Spix's macaw (Cyanopsitta spixii), have been severely impacted by PDD

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