title: Recovery of divergent avian bornaviruses from cases of proventricular dilatation disease: identification of a candidate etiologic agent.
abstract: BACKGROUND
  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. 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.
  
  
  RESULTS
  Analysis 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.
  
  
  CONCLUSIONS
  These 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.
authors.affiliation: Departments of Biochemistry, Microbiology and Medicine, Howard Hughes Medical Institute, University of California, San Francisco, 94143, USA. amy@derisilab.ucsf.edu
authors.forename: Amy L
authors.initials: AL
authors.lastname: Kistler
authors.forename: Ady
authors.initials: A
authors.lastname: Gancz
authors.forename: Susan
authors.initials: S
authors.lastname: Clubb
authors.forename: Peter
authors.initials: P
authors.lastname: Skewes-Cox
authors.forename: Kael
authors.initials: K
authors.lastname: Fischer
authors.forename: Katherine
authors.initials: K
authors.lastname: Sorber
authors.forename: Charles Y
authors.initials: CY
authors.lastname: Chiu
authors.forename: Avishai
authors.initials: A
authors.lastname: Lublin
authors.forename: Sara
authors.initials: S
authors.lastname: Mechani
authors.forename: Yigal
authors.initials: Y
authors.lastname: Farnoushi
authors.forename: Alexander
authors.initials: A
authors.lastname: Greninger
authors.forename: Christopher C
authors.initials: CC
authors.lastname: Wen
authors.forename: Scott B
authors.initials: SB
authors.lastname: Karlene
authors.forename: Don
authors.initials: D
authors.lastname: Ganem
authors.forename: Joseph L
authors.initials: JL
authors.lastname: DeRisi
mesh_terms: D000818:Animals; D001483:Base Sequence; D001715:Bird Diseases / Q000821:virology*; D001717:Birds / Q000821:virology*; D028981:Bornaviridae / Q000235:genetics / Q000302:isolation & purification* / Q000472:pathogenicity; D003389:Cranial Nerve Diseases / Q000662:veterinary* / Q000821:virology; D004108:Dilatation, Pathologic / Q000662:veterinary; D008969:Molecular Sequence Data; D020411:Oligonucleotide Array Sequence Analysis; D010802:Phylogeny; D011531:Proventriculus; D016415:Sequence Alignment; D013272:Stomach Diseases / Q000662:veterinary* / Q000821:virology