Identification of a previously undescribed divergent virus from the Flaviviridae family in an outbreak of equine serum hepatitis
Identification of a previously undescribed divergent virus from the Flaviviridae family in an outbreak of equine serum hepatitis
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DOI：
10.1073/pnas.1219217110
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发表时间：
2013-04-09
影响因子：
11.1
通讯作者：
Kistler, Amy L.
中科院分区：
文献类型：
--
作者：
Chandriani, Sanjay;Skewes-Cox, Peter;Kistler, Amy L.
泰勒氏病是一种与马血制品给药相关的马急性肝炎;其病原体近世纪来一直未知。在这里，我们使用大规模平行测序来探索最近Theiler病爆发的样本。短序列读段的元转录组学分析从以前未描述的黄病毒科病毒中鉴定出10.5 kb的序列，我们将其命名为"泰勒病相关病毒"（TDAV）。系统发育分析将TDAV与最近提出的Pegivirus属的GB病毒聚类，尽管它与其最近的亲戚GB病毒D仅共享35.3%的氨基酸同一性。来自三个不同地点的其他马的流行病学调查支持TDAV感染和急性血清肝炎之间的关联。用TDAV阳性血浆对马进行的实验性接种提供了证据，证明在肝损伤之前存在数周的病毒血症，并且肝脏疾病可能与病毒血症水平不直接相关。像丙型肝炎病毒一样，已知引起肝炎的最具特征的黄病毒科物种，我们发现TDAV能够有效地胃肠外传播，产生与从亚临床感染到临床肝炎的多种临床表现相关的急性和慢性感染。
Theiler's disease is an acute hepatitis in horses that is associated with the administration of equine blood products; its etiologic agent has remained unknown for nearly a century. Here, we used massively parallel sequencing to explore samples from a recent Theiler's disease outbreak. Metatranscriptomic analysis of the short sequence reads identified a 10.5-kb sequence from a previously undescribed virus of the Flaviviridae family, which we designate "Theiler's disease-associated virus" (TDAV). Phylogenetic analysis clusters TDAV with GB viruses of the recently proposed Pegivirus genus, although it shares only 35.3% amino acid identity with its closest relative, GB virus D. An epidemiological survey of additional horses from three separate locations supports an association between TDAV infection and acute serum hepatitis. Experimental inoculation of horses with TDAV-positive plasma provides evidence that several weeks of viremia preceded liver injury and that liver disease may not be directly related to the level of viremia. Like hepatitis C virus, the best characterized Flaviviridae species known to cause hepatitis, we find TDAV is capable of efficient parenteral transmission, engendering acute and chronic infections associated with a diversity of clinical presentations ranging from subclinical infection to clinical hepatitis.