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
Departments of Biochemistry, Microbiology and Medicine, Howard Hughes Medical Institute, University of California, San Francisco, 94143, USA.
Virol J. 2008 Jul 31;5:88. doi: 10.1186/1743-422X-5-88.
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.
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.
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.
嗉囊扩张病(PDD)是一种致命性疾病,威胁着全球范围内的家养和野生鹦鹉类鸟类。其特征为中枢和外周神经系统神经节出现淋巴细胞和浆细胞浸润,导致中枢神经系统功能紊乱以及肠道运动失调和相关消瘦。近40年来,一直怀疑PDD由病毒引起,但迄今为止,尚未有候选病原体能被可靠地与该疾病联系起来。
使用全病毒微阵列对在不同大陆独立收集的2个PDD病例对照系列进行分析,结果显示,62.5%的PDD病例(5/8)出现博尔纳病毒杂交信号,而对照组无一出现(0/8)。利用超高通量测序从其中1例病毒阳性的PDD病例中获得了完整的病毒基因组序列。这揭示了该病原体具有类似博尔纳病毒的基因组结构,且与所有先前的博尔纳病毒分离株在序列上存在高度差异。我们提议将该病原体命名为禽博尔纳病毒(ABV)。对另一组独立收集的PDD病例和对照进行进一步的ABV特异性PCR分析,结果显示PDD病例的ABV检出率(71%,n = 7)与对照组(0%,n = 14)相比存在显著差异(P = 0.01;Fisher精确检验)。我们目前从这些病例及另一组病例中总共分离出16株ABV,对其部分序列分析显示至少存在5个不同的ABV遗传亚组。
这些研究清楚地证明了存在一个包含显著多样博尔纳病毒的禽类宿主库,并为寻找PDD的病原体提供了一个令人信服的候选病原体。