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

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

The cause of PDD is unknown, but several studies have raised the possibility that PDD may be caused by a viral pathogen. Evidence for an infectious etiology stems from the initial outbreaks of Macaw Wasting Disease, and other subsequent outbreaks of PDD [2, 10] . Reports of pleomorphic virus-like particles of variable size (30-250 nm) observed in tissues of PDD affected birds [8] led to the proposal that paramyxovirus (PMV) may cause the disease; however, serological data has shown that PDD affected birds lack detectable antibodies against PMV of serotypes 1-4, 6, and 7, as well as against avian herpes viruses, polyomavirus, and avian encephalitis virus [3] . Similarly, a proposed role for equine encephalitis virus in PDD has been ruled out [11] . Enveloped virus-like particles of approximately 80 nm in diameter derived from the feces of affected birds have been shown to produce cytopathic effect in monolayers of macaw embryonic cells [12] , but to date no reports confirming these results or identifying this possible agent have been published. Like-wise, adeno-like viruses, enteroviruses, coronaviruses and reoviruses have also been sporadically documented in tissues or excretions of affected birds [3, 13, 14] yet in each case, follow-up evidence for reproducible isolation specifically from PDD cases or identification of these candidate agents has not been reported. Thus, the etiology of PDD has remained an open question.