Drave S A, Debing Y, Walter S, Todt D, Engelmann M, Friesland M, Wedemeyer H, Neyts J, Behrendt P, Steinmann E
Institute for Experimental Virology, TWINCORE, Centre for Experimental and Clinical Infection Research, A joint venture between the Medical School Hannover (MHH) and the Helmholtz Centre for Infection Research (HZI), Hannover, Germany.
Department of Microbiology and Immunology, Rega Institute for Medical Research, KU Leuven, Leuven, Belgium.
J Viral Hepat. 2016 Jul;23(7):512-21. doi: 10.1111/jvh.12515. Epub 2016 Feb 19.
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-Barré 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.
戊型肝炎病毒（HEV）是人类戊型肝炎的病原体，属于肝炎病毒科正戊型肝炎病毒属。感染通常会导致急性肝炎，可能发展为暴发性肝炎，尤其是在孕妇和已有肝病的患者中，或者可能演变为慢性状态，特别是在免疫抑制个体中。已证明HEV会产生一系列肝外表现，包括再生障碍性贫血、急性甲状腺炎、肾小球肾炎以及神经系统疾病，如格林-巴利综合征、神经性肌萎缩和脑炎。这些神经损伤的发病机制在很大程度上仍不清楚，而且HEV是否能直接感染神经元细胞也不确定。在本研究中，我们调查了HEV是否能够在人神经元来源的细胞系中完成病毒生命周期，如神经上皮瘤（SK-N-MC）、促结缔组织增生性小脑髓母细胞瘤（DAOY）、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。用HEV高斯荧光素酶报告病毒转染这些细胞后，所有测试的细胞系均支持HEV RNA复制。此外，通过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物。少突胶质细胞系M03.13对HEV细胞进入具有易感性。总之，这些结果表明HEV的嗜性不限于肝脏，并且HEV可能在神经元来源的组织中完成完整的病毒生命周期，这解释了HEV感染期间的神经系统疾病。
