Intracellular localization of the hepatitis B virus HBx protein
Intracellular localization of the hepatitis B virus HBx protein
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DOI：
10.1099/0022-1317-82-4-871
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发表时间：
2001-04-01
影响因子：
3.8
通讯作者：
King, IA
中科院分区：
文献类型：
--
作者：
Henkler, F;Hoare, J;King, IA
乙型肝炎病毒（HBV）X蛋白（HBx）最初被认为是一种病毒转录激活剂，但其功能机制仍不清楚。在这项研究中，我们分析了转染细胞中 HBx 的细胞内定位，并证明其区室化取决于总体表达水平。 HBx 完全或主要位于弱表达细胞的细胞核中。然而，细胞水平升高与其在细胞质中的积累相关，表明 HBx 的核区室化能力可能有限。细胞质 HBx 被检测为点状颗粒染色或分散的细颗粒图案。我们使用共聚焦显微镜进一步分析了详细的细胞质区室化，结果显示 HBx 与内质网、质膜或溶酶体没有关联，但与线粒体有显着关联。然而，细胞质 HBx 的主要部分并不位于线粒体中，表明存在两个明显分隔的细胞质群体。此外，高水平的HBx表达导致线粒体分布异常，包括成团和细胞器聚集，而在较低表达水平时未观察到这种情况。这里提供的数据为 HBx 的划分提供了新的见解，并且可能对于未来评估其在病毒生命周期和 HBV 相关肝病病理学中的功能很重要。
The hepatitis B virus (HBV) X protein (HBx) was originally suggested to be a viral transcriptional activator, but its functional mechanisms are still unclear. In this study we have analysed the intracellular localization of HBx in transfected cells and demonstrate that its compartmentalization is dependent on overall expression levels. HBx was exclusively or predominantly localized in the nuclei in weakly expressing cells. However, elevated cellular levels correlated with its accumulation in the cytoplasm, suggesting that the capacity of HBx for nuclear compartmentalization might be limited. Cytoplasmic HBx was detected either as punctate granular staining or in dispersed, finely granular patterns. We have further analysed the detailed cytoplasmic compartmentalization, using confocal microscopy, and show no association with the endoplasmic reticulum, plasma membrane or lysosomes, but a substantial association of HBx with mitochondria. However, a major fraction of cytoplasmic HBx did not localize in mitochondria, indicating the presence of two distinctly compartmentalized cytoplasmic populations. Furthermore, high levels of HBx expression led to an abnormal mitochondrial distribution, involving clumping and organelle aggregation, which was not observed at lower expression levels. The data presented here provide novel insights into the compartmentalization of HBx and may prove important for future evaluations of its functions, both in the viral life-cycle and in the pathology of HBV-related liver disease.