HBV Core Protein Is in Flux between Cytoplasmic, Nuclear, and Nucleolar Compartments.
HBV Core Protein Is in Flux between Cytoplasmic, Nuclear, and Nucleolar Compartments.
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DOI：
10.1128/mbio.03514-20
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发表时间：
2021-02-09
期刊：
影响因子：
6.4
通讯作者：
Zlotnick A
中科院分区：
文献类型：
--
作者：
Nair S;Zlotnick A
B型肝炎病毒（HBV）核心蛋白（Cp）存在于感染肝细胞的细胞核和细胞质中;然而，它优先分离到与疾病状态相关的特定区室。Cp的这种细胞内分配的调节仍然不清楚。在本文中，我们报告说，细胞隔室填充和腾出的Cp在一个时间和浓度依赖性的方式在转染和感染。在转染后的早期，Cp以二聚体状态优先定位于核仁。随后，核仁区室被清空，Cp主要是核，大部分蛋白质处于组装状态。核定位之后是细胞范围内的分布，然后Cp变成专门的细胞质。在感染期间观察到Cp运动的相同趋势。推定的核仁滞留信号已被确定，似乎是结构依赖性。Cp从细胞核的输出涉及CRM 1的输出。时间依赖性通量可以通过修改Cp浓度来概括，这表明通过达到阈值浓度来调节过渡。
Hepatitis B virus (HBV) core protein (Cp) can be found in the nucleus and cytoplasm of infected hepatocytes; however, it preferentially segregates to a specific compartment correlating with disease status. Regulation of this intracellular partitioning of Cp remains obscure. In this paper, we report that cellular compartments are filled and vacated by Cp in a time- and concentration-dependent manner in both transfections and infections. At early times after transfection, Cp, in a dimeric state, preferentially localizes to the nucleolus. Later, the nucleolar compartment is emptied and Cp progresses to being predominantly nuclear, with a large fraction of the protein in an assembled state. Nuclear localization is followed by cell-wide distribution, and then Cp becomes exclusively cytoplasmic. The same trend in Cp movement is seen during an infection. Putative nucleolar retention signals have been identified and appear to be structure dependent. Export of Cp from the nucleus involves the CRM1 exportin. Time-dependent flux can be recapitulated by modifying Cp concentration, suggesting transitions are regulated by reaching a threshold concentration.