Extra-hepatic replication and infection of hepatitis E virus in neuronal-derived cells
Extra-hepatic replication and infection of hepatitis E virus in neuronal-derived cells
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DOI：
10.1111/jvh.12515
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发表时间：
2016-07-01
影响因子：
2.5
通讯作者：
Steinmann, E.
中科院分区：
文献类型：
--
作者：
Drave, S. A.;Debing, Y.;Steinmann, E.
戊型肝炎病毒（HEV）是人类戊型肝炎的病原体，是肝炎病毒科正肝炎病毒属的一员。感染通常导致急性肝炎，可变为暴发性肝炎，特别是在孕妇和既往存在肝脏疾病的患者中，或可能演变为慢性状态，特别是在免疫抑制的个体中。戊肝病毒已被证明可产生一系列肝外表现，包括再生障碍性贫血、急性甲状腺炎、肾小球肾炎以及格林-巴利综合征、神经性肌萎缩症和脑炎等神经系统疾病。这些神经损伤的发病机制在很大程度上仍不清楚，也不确定HEV是否能直接感染神经元细胞。在这项研究中，我们研究了HEV是否能够在人类神经元来源的细胞系如神经上皮瘤（SK-N-MC）、小脑髓母细胞瘤（道y）、多形性胶质母细胞瘤（DBTRG）、胶质母细胞瘤星形细胞瘤（U-373 MG）和少突胶质细胞（M03.13）细胞中完成病毒生命周期。用HEV高斯荧光素酶报告病毒转染这些细胞后，所有测试的细胞系都支持HEV RNA复制。此外，利用HEV抗原ELISA检测细胞外和细胞内的病毒衣壳，作为病毒组装和释放的标志。少突胶质细胞系M03.13允许HEV细胞进入。总之，这些结果表明，HEV的嗜性并不局限于肝脏，并且HEV可能在神经元源性组织中完成完整的病毒生命周期，解释了HEV感染期间的神经疾病。
Hepatitis E virus (HEV) is the causative agent of hepatitis E in humans and a member of the genus Orthohepevirus in the family Hepeviridae. Infection usually leads to acute hepatitis that can become fulminant, particularly among pregnant women and in patients with preexisting liver disease, or may evolve to a chronic state, especially in immunosuppressed individuals. HEV has been shown to produce a range of extra-hepatic manifestations including aplastic anaemia, acute thyroiditis, glomerulonephritis as well as neurological disorders such as Guillain-Barre syndrome, neuralgic amyotrophy and encephalitis. The pathogenesis of these neurological injuries remains largely unknown, and it is also uncertain whether or not HEV can directly infect neuronal cells. In this study, we investigated whether HEV is capable of completing the viral life cycle in human neuronal-derived cell lines such as neuroepithelioma (SK-N-MC), desmoplastic cerebellar medulloblastoma (DAOY), glioblastoma multiforme (DBTRG), glioblastoma astrocytoma (U-373 MG) and oligodendrocytic (M03.13) cells. Following transfection of these cells with HEV Gaussia luciferase reporter virus, all tested cell lines supported HEV RNA replication. Furthermore, extra-and intracellular viral capsid was detected by an HEV antigen ELISA as a marker for virus assembly and release. Permissiveness for HEV cell entry could be demonstrated for the oligodendrocytic cell line M03.13. In conclusion, these results indicate that HEV tropism is not restricted to the liver and HEV can potentially complete the full viral life cycle in neuronal-derived tissues explaining neurologic disorders during HEV infection.