Department of Gastroenterology and Hepatology, Erasmus MC-University Medical Center, Rotterdam, The Netherlands.
Medical Faculty, Kunming University of Science and Technology, China.
J Infect Dis. 2017 Apr 15;215(8):1197-1206. doi: 10.1093/infdis/jix079.
Hepatitis E virus (HEV), as a hepatotropic virus, is supposed to exclusively infect the liver and only cause hepatitis. However, a broad range of extrahepatic manifestations (in particular, idiopathic neurological disorders) have been recently reported in association with its infection. In this study, we have demonstrated that various human neural cell lines (embryonic stem cell-derived neural lineage cells) induced pluripotent stem cell-derived human neurons and primary mouse neurons are highly susceptible to HEV infection. Treatment with interferon-α or ribavirin, the off-label antiviral drugs for chronic hepatitis E, exerted potent antiviral activities against HEV infection in neural cells. More importantly, in mice and monkey peripherally inoculated with HEV particles, viral RNA and protein were detected in brain tissues. Finally, patients with HEV-associated neurological disorders shed the virus into cerebrospinal fluid, indicating a direct infection of their nervous system. Thus, HEV is neurotropic in vitro, and in mice, monkeys, and possibly humans. These results challenge the dogma of HEV as a pure hepatotropic virus and suggest that HEV infection should be considered in the differential diagnosis of idiopathic neurological disorders.
戊型肝炎病毒（HEV）作为一种嗜肝病毒，本应仅感染肝脏，仅引起肝炎。然而，最近有大量的肝外表现（特别是特发性神经疾病）与它的感染有关。在这项研究中，我们证明了各种人类神经细胞系（胚胎干细胞衍生的神经谱系细胞）、诱导多能干细胞衍生的人类神经元和原代小鼠神经元极易被 HEV 感染。用干扰素-α或利巴韦林（慢性戊型肝炎的非标签抗病毒药物）治疗在神经细胞中对 HEV 感染具有强大的抗病毒活性。更重要的是，在经外周接种 HEV 颗粒的小鼠和猴子中，脑组织中检测到病毒 RNA 和蛋白。最后，HEV 相关神经疾病患者的病毒排入脑脊液中，表明其神经系统受到直接感染。因此，HEV 在体外具有嗜神经性，并且在小鼠、猴子，可能还有人类中都是如此。这些结果对 HEV 作为一种纯嗜肝病毒的教条提出了挑战，并表明在特发性神经疾病的鉴别诊断中应考虑 HEV 感染。
