Hepatoma polarization limits CD81 and hepatitis C virus dynamics
Hepatoma polarization limits CD81 and hepatitis C virus dynamics
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DOI：
10.1111/cmi.12047
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发表时间：
2013-03-01
影响因子：
3.4
通讯作者：
McKeating, J. A.
中科院分区：
文献类型：
--
作者：
Harris, H. J.;Clerte, C.;McKeating, J. A.
许多病毒在宿主入侵期间靶向极化的上皮顶端。相反，丙型肝炎病毒（HCV）在极化肝实质中接合肝细胞基底表面的受体。肝细胞极化通过未定义的机制限制HCV进入。鉴于最近的报道强调了受体迁移率在病原体进入中的作用，我们使用光漂白和单粒子跟踪后的实时荧光恢复研究了肝细胞极化对病毒受体和HCV假粒子（HCVpp）动力学的影响。肝癌极化降低了基底膜的CD 81和HCVpp动力学。由于细胞极化伴随着肌动蛋白细胞骨架的变化，并且CD 81通过其C-末端与肌动蛋白连接，因此我们研究了缺乏C-末端尾的突变型CD 81（CD 81 C）的动力学及其对HCVpp流动性和感染的影响。与非极化细胞中的野生型蛋白相比，CD 81 C显示出受限轨迹的频率增加和布朗扩散分子的减少。然而，这些变化在极化细胞中并不明显。HCVpp显示表达CD 81 C的非极化细胞的布朗扩散和感染显著减少。总之，这些数据突出了CD 81的动态性质，并证明了CD 81侧向扩散以极化依赖性方式调节HCV感染的作用。
Many viruses target the polarized epithelial apex during host invasion. In contrast, hepatitis C virus (HCV) engages receptors at the basal surface of hepatocytes in the polarized liver parenchyma. Hepatocyte polarization limits HCV entry by undefined mechanism(s). Given the recent reports highlighting a role for receptor mobility in pathogen entry, we studied the effect(s) of hepatocyte polarization on viral receptor and HCV pseudoparticle (HCVpp) dynamics using real-time fluorescence recovery after photobleaching and single particle tracking. Hepatoma polarization reduced CD81 and HCVpp dynamics at the basal membrane. Since cell polarization is accompanied by changes in the actin cytoskeleton and CD81 links to actin via its C-terminus, we studied the dynamics of a mutant CD81 lacking a C-terminal tail (CD81C) and its effect(s) on HCVpp mobility and infection. CD81C showed an increased frequency of confined trajectories and a reduction of Brownian diffusing molecules compared to wild-type protein in non-polarized cells. However, these changes were notobserved in polarized cells. HCVpp showed a significant reduction in Brownian diffusion and infection of CD81C expressing non-polarized cells. In summary, these data highlight the dynamic nature of CD81 and demonstrate a role for CD81 lateral diffusion to regulate HCV infection in a polarization-dependent manner.