Shi R, Soomro M H, She R, Yang Y, Wang T, Wu Q, Li H, Hao W
Laboratory of Animal Pathology and Public Health, Key Laboratory of Zoonosis of Ministry of Agriculture, College of Veterinary Medicine, China Agriculture University, Beijing, China.
J Viral Hepat. 2016 Nov;23(11):930-939. doi: 10.1111/jvh.12557. Epub 2016 Jun 21.
Neurologic dysfunctions such as Guillain-Barre' syndrome, encephalitis, meningitis and transverse myelitis occur frequently in patients with hepatitis E virus (HEV) infection, and this study was conducted to better characterize the role of HEV in the pathogenesis of neurologic disorders. Genotype 4 strain of swine HEV was used to inoculate Mongolian gerbils. Reverse transcription-nested polymerase chain reaction (RT-nPCR), ELISA, histopathology, ultrastructural pathology and enzyme immunohistochemistry method were conducted to investigate the replication and localization of HEV in the central nervous system (CNS) and the consequent pathological changes. Both positive- and negative-strand HEV RNA was detectable in brain and spinal cord from 7 to 28 dpi (days postinoculation) via RT-nPCR. Various pathological changes such as perineural invasion, neuron necrosis, microglia nodule, lymphocyte infiltration, perivascular cuff and myelin degeneration were observed in HEV-positive brains and spinal cords. Immunohistochemical (IHC) staining targeting on HEV ORF2 protein revealed positive signals concentrated mainly in the cytoplasm of neuron, ependymal epithelium and choroid plexus area. Positive area density of ZO-1 (zonula occludens-1) in brain of HEV-positive gerbils decreased, while the GFAP (glial fibrillary acidic protein) expression was upregulated compared with control groups. These results provide strong evidence that HEV is able to damage the blood-brain barrier (BBB), replicate in brain and spinal cord, and hammer the causative role of HEV in the pathogenesis of neurologic disorders.
诸如吉兰 - 巴雷综合征、脑炎、脑膜炎和横贯性脊髓炎等神经功能障碍在戊型肝炎病毒（HEV）感染患者中频繁发生，本研究旨在更好地阐明HEV在神经疾病发病机制中的作用。采用猪HEV 4型毒株接种蒙古沙鼠。运用逆转录巢式聚合酶链反应（RT - nPCR）、酶联免疫吸附测定（ELISA）、组织病理学、超微结构病理学和酶免疫组织化学方法，研究HEV在中枢神经系统（CNS）中的复制与定位以及由此产生的病理变化。通过RT - nPCR在接种后7至28天（dpi）的脑和脊髓中均可检测到正链和负链HEV RNA。在HEV阳性的脑和脊髓中观察到各种病理变化，如神经周围浸润、神经元坏死、小胶质细胞结节、淋巴细胞浸润、血管周围套袖形成和髓鞘变性。针对HEV ORF2蛋白的免疫组织化学（IHC）染色显示阳性信号主要集中在神经元、室管膜上皮和脉络丛区域的细胞质中。与对照组相比，HEV阳性沙鼠脑中紧密连接蛋白1（ZO - 1）的阳性面积密度降低，而胶质纤维酸性蛋白（GFAP）表达上调。这些结果提供了有力证据，表明HEV能够破坏血脑屏障（BBB），在脑和脊髓中复制，并证实了HEV在神经疾病发病机制中的致病作用。
