Hepatitis B Virus Capsid: The Core in Productive Entry and Covalently Closed Circular DNA Formation.
Hepatitis B Virus Capsid: The Core in Productive Entry and Covalently Closed Circular DNA Formation.
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DOI：
10.3390/v15030642
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发表时间：
2023-02-28
期刊：
影响因子：
--
通讯作者：
Hu J
中科院分区：
文献类型：
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作者：
Mendenhall MA;Hong X;Hu J
乙型肝炎病毒 (HBV) 依靠核心蛋白 (HBc) 来建立有效感染，定义为共价闭合环化 DNA (cccDNA) 的形成，以及执行 cccDNA 形成后生命周期的几乎每一步。 HBc 的多个拷贝形成二十面体衣壳壳，其包裹病毒前基因组 RNA (pgRNA) 并促进 pgRNA 逆转录为衣壳内的松弛环状 DNA (rcDNA)。在感染过程中，完整的 HBV 病毒体除了含有 rcDNA 的内部核衣壳外，还包含外被膜层，通过内吞作用进入人肝细胞，并穿过内体区室和胞质溶胶，将其 rcDNA 递送至细胞核，产生 cccDNA。此外，在细胞质核衣壳中新形成的子代rcDNA也被递送至同一细胞的细胞核，以在称为细胞内cccDNA扩增或回收的过程中形成更多cccDNA。在这里，我们重点关注最近的证据，证明使用 HBc 突变和小分子抑制剂获得的 HBc 在从头感染与回收过程中影响 cccDNA 形成的不同作用。这些结果表明 HBc 在确定感染期间的 HBV 运输以及核衣壳解体（脱壳）以释放 rcDNA（对于 cccDNA 形成至关重要的事件）方面发挥着关键作用。 HBc 可能通过与宿主因子的相互作用在这些过程中发挥作用，这对 HBV 宿主趋向性至关重要。更好地了解 HBc 在 HBV 进入、cccDNA 形成和宿主物种趋向性中的作用，应能加速针对 HBc 和 cccDNA 开发 HBV 治疗方法的持续努力，并促进为基础研究和药物开发建立方便的动物模型。
Hepatitis B virus (HBV) relies on the core protein (HBc) to establish productive infection, as defined by the formation of the covalently closed circularized DNA (cccDNA), as well as to carry out almost every step of the lifecycle following cccDNA formation. Multiple copies of HBc form an icosahedral capsid shell that encapsidates the viral pregenomic RNA (pgRNA) and facilitates the reverse transcription of pgRNA to a relaxed circular DNA (rcDNA) within the capsid. During infection, the complete HBV virion, which contains an outer envelope layer in addition to the internal nucleocapsid containing rcDNA, enters human hepatocytes via endocytosis and traffics through the endosomal compartments and the cytosol to deliver its rcDNA to the nucleus to produce cccDNA. In addition, progeny rcDNA, newly formed in cytoplasmic nucleocapsids, is also delivered to the nucleus in the same cell to form more cccDNA in a process called intracellular cccDNA amplification or recycling. Here, we focus on recent evidence demonstrating differential effects of HBc in affecting cccDNA formation during de novo infection vs. recycling, obtained using HBc mutations and small molecule inhibitors. These results implicate a critical role of HBc in determining HBV trafficking during infection, as well as in nucleocapsid disassembly (uncoating) to release rcDNA, events essential for cccDNA formation. HBc likely functions in these processes via interactions with host factors, which contributes critically to HBV host tropism. A better understanding of the roles of HBc in HBV entry, cccDNA formation, and host species tropism should accelerate ongoing efforts to target HBc and cccDNA for the development of an HBV cure and facilitate the establishment of convenient animal models for both basic research and drug development.
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DOI：
10.3390/v9030056
发表时间：
2017-03-21
期刊：
Viruses
影响因子：
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作者：
Hu J;Liu K
通讯作者：
Liu K
影响因子：
5.4
作者：
GUIDOTTI, LG;MATZKE, B;CHISARI, FV
通讯作者：
CHISARI, FV
影响因子：
3.4
作者：
Herrscher, Charline;Pastor, Florentin;Blanchard, Emmanuelle
通讯作者：
Blanchard, Emmanuelle
影响因子：
13.5
作者：
Funk, Anneke;Mhamdi, Mouna;Sirma, Hueseyin
通讯作者：
Sirma, Hueseyin
影响因子：
6.7
作者：
通讯作者：
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