Hepatitis C virus infects the endothelial cells of the blood-brain barrier.
Hepatitis C virus infects the endothelial cells of the blood-brain barrier.
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DOI：
10.1053/j.gastro.2011.11.028
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发表时间：
2012-03
期刊：
影响因子：
29.4
通讯作者：
McKeating JA
中科院分区：
文献类型：
--
作者：
Fletcher NF;Wilson GK;Murray J;Hu K;Lewis A;Reynolds GM;Stamataki Z;Meredith LW;Rowe IA;Luo G;Lopez-Ramirez MA;Baumert TF;Weksler B;Couraud PO;Kim KS;Romero IA;Jopling C;Morgello S;Balfe P;McKeating JA
丙型肝炎病毒（HCV）感染可导致进行性肝病，并与多种肝外综合征相关，包括中枢神经系统（CNS）异常。然而，目前尚不清楚这种认知异常是否是全身性疾病、肝功能受损或病毒感染中枢神经系统的功能。我们通过定量聚合酶链反应、免疫化学和共聚焦成像分析，测量了10名感染者（和3名未感染者作为对照）和人脑微血管内皮细胞脑组织样本中HCV RNA水平和病毒进入受体的表达。HCV假颗粒和细胞培养衍生的HCV被用于研究内皮细胞支持病毒进入和复制的能力。利用定量聚合酶链反应，我们检测到感染者脑组织中的HCV RNA水平明显低于肝脏样本。脑微血管内皮和脑内皮细胞表达所有已知的HCV进入受体。两种独立衍生的脑内皮细胞系hC-MEC/D3和HBMEC支持HCV进入和复制。这些过程被抗进入因子CD81、清道夫受体BI和claudin-1的抗体所抑制；干扰素;以及抑制NS3蛋白酶和NS5B聚合酶的试剂。HCV感染促进内皮通透性和细胞凋亡。人脑内皮细胞表达支持HCV进入和复制的功能性受体。病毒感染中枢神经系统可能导致hcv相关的神经病变。
Hepatitis C virus (HCV) infection leads to progressive liver disease and is associated with a variety of extrahepatic syndromes, including central nervous system (CNS) abnormalities. However, it is unclear whether such cognitive abnormalities are a function of systemic disease, impaired hepatic function, or virus infection of the CNS. We measured levels of HCV RNA and expression of the viral entry receptor in brain tissue samples from 10 infected individuals (and 3 uninfected individuals, as controls) and human brain microvascular endothelial cells by using quantitative polymerase chain reaction and immunochemical and confocal imaging analyses. HCV pseudoparticles and cell culture–derived HCV were used to study the ability of endothelial cells to support viral entry and replication. Using quantitative polymerase chain reaction, we detected HCV RNA in brain tissue of infected individuals at significantly lower levels than in liver samples. Brain microvascular endothelia and brain endothelial cells expressed all of the recognized HCV entry receptors. Two independently derived brain endothelial cell lines, hC-MEC/D3 and HBMEC, supported HCV entry and replication. These processes were inhibited by antibodies against the entry factors CD81, scavenger receptor BI, and claudin-1; by interferon; and by reagents that inhibit NS3 protease and NS5B polymerase. HCV infection promotes endothelial permeability and cellular apoptosis. Human brain endothelial cells express functional receptors that support HCV entry and replication. Virus infection of the CNS might lead to HCV-associated neuropathologies.
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影响因子：
--
作者：
Morgello, S;Estanislao, L;Sharp, V
通讯作者：
Sharp, V
影响因子：
56.9
作者：
Jopling, CL;Yi, MK;Sarnow, P
通讯作者：
Sarnow, P
影响因子：
4.4
作者：
Lalor, PF;Edwards, S;Adams, DH
通讯作者：
Adams, DH
影响因子：
13.5
作者：
Krieger, Sophie E.;Zeisel, Mirjam B.;Baumert, Thomas F.
通讯作者：
Baumert, Thomas F.
影响因子：
6.4
作者：
Fishman, Sarah L.;Murray, Jacinta M.;Branch, Andrea D.
通讯作者：
Branch, Andrea D.