Evidence of Hepatitis E virus breaking through the blood-brain barrier and replicating in the central nervous system
Evidence of Hepatitis E virus breaking through the blood-brain barrier and replicating in the central nervous system
复制标题
戊型肝炎病毒突破血脑屏障并在中枢神经系统中复制的证据
DOI：
10.1111/jvh.12557
复制
发表时间：
2016-11-01
影响因子：
2.5
通讯作者：
Hao, W.
中科院分区：
文献类型：
--
作者：
Shi, R.;Soomro, M. H.;Hao, W.
戊型肝炎病毒（HEV）感染患者经常出现格林-巴利综合征、脑炎、脑膜炎和横脊炎等神经功能障碍，本研究旨在更好地表征戊型肝炎病毒在神经系统疾病发病机制中的作用。采用猪HEV基因4型毒株接种蒙古沙鼠。采用逆转录巢式聚合酶链反应（RT-nPCR）、ELISA、组织病理学、超微结构病理学和酶免疫组化等方法研究HEV在中枢神经系统（CNS）的复制、定位及其病理改变。通过RT-nPCR，在接种后7 - 28 dpi（接种后天）的脑组织和脊髓中检测到阳性链和阴性链HEV RNA。hev阳性脑组织和脊髓出现神经周围浸润、神经元坏死、小胶质细胞结节、淋巴细胞浸润、血管周围袖带及髓鞘变性等病理改变。针对HEV ORF2蛋白的免疫组化（IHC）染色显示阳性信号主要集中在神经元、室管膜上皮和脉络膜丛区细胞质中。与对照组相比，hev阳性沙鼠脑组织ZO-1（闭塞带-1）阳性区密度降低，胶质纤维酸性蛋白（GFAP）表达上调。这些结果提供了强有力的证据，证明HEV能够破坏血脑屏障（BBB），在脑和脊髓中复制，并明确了HEV在神经系统疾病发病机制中的致病作用。
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.