Itinerary of hepatitis B viruses: Delineation of restriction points critical for infectious entry
Itinerary of hepatitis B viruses: Delineation of restriction points critical for infectious entry
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DOI：
10.1128/jvi.78.15.8289-8300.2004
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发表时间：
2004-08-01
影响因子：
5.4
通讯作者：
Sirma, H
中科院分区：
文献类型：
--
作者：
Funk, A;Mhamdi, M;Sirma, H
对人类B型肝炎病毒感染所必需的细胞决定簇知之甚少。以鸭乙型肝炎病毒B为模型，我们首先建立了一种灵敏的病毒粒子和亚病毒颗粒的结合试验，随后阐明了早期病毒进入步骤的特征。发现感染过程始于病毒颗粒附着在肝细胞上的少量结合位点（每个细胞约104个）。病毒内化在不到3小时内完全完成，但随后是一段前所未有的长度，约14小时，直到完成病毒基因组的核输入。病毒进入后的步骤依赖于完整的微管和它们的动态营业额，但不依赖于肌动蛋白细胞骨架。值得注意的是，病毒颗粒的细胞质运输和核共价闭合环状DNA的出现仅在特定的时间段和特定的时间段在进入期间需要微管。总之，这些数据首次披露了一系列步骤及其动力学，这些步骤和动力学对于B型肝炎病毒进入肝细胞是必不可少的，并且与迄今为止报道的任何其他病毒的步骤和动力学不同。
Little is known about cellular determinants essential for human hepatitis B virus infection. Using the duck hepatitis B virus as a model, we first established a sensitive binding assay for both virions and subviral particles and subsequently elucidated the characteristics of the early viral entry steps. The infection itinerary was found to initiate with the attachment of viral particles to a low number of binding sites on hepatocytes (about 104 per cell). Virus internalization was fully accomplished in less than 3 h but was then followed by a period of unprecedented length, about 14 h, until completion of nuclear import of the viral genome. Steps subsequent to virus entry depended on both intact microtubules and their dynamic turnover but not on actin cytoskeleton. Notably, cytoplasmic trafficking of viral particles and emergence of nuclear covalently closed circular DNA requires microtubules during entry only at and for specific time periods. Taken together, these data disclose for the first time a series of steps and their kinetics that are essential for the entry of hepatitis B viruses into hepatocytes and are different from those of any other virus reported so far.