Does a cdc2 kinase-like recognition motif on the core protein of hepadnaviruses regulate assembly and disintegration of capsids?
Does a cdc2 kinase-like recognition motif on the core protein of hepadnaviruses regulate assembly and disintegration of capsids?
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DOI：
10.1128/jvi.75.4.2024-2028.2001
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发表时间：
2001-02-01
影响因子：
5.4
通讯作者：
Seeger, C
中科院分区：
文献类型：
--
作者：
Barrasa, MI;Guo, JT;Seeger, C
嗜肝DNA病毒是包膜病毒，每种病毒具有包装在二十面体核衣壳中的DNA基因组，所述二十面体核衣壳是病毒DNA合成的位点。在存在包膜蛋白的情况下，含有核衣壳的DNA组装成病毒体并分泌，但在不存在这些蛋白的情况下，核衣壳将病毒DNA递送到细胞核中。据推测，这一步骤与感染开始期间病毒DNA的递送相同。不幸的是，触发亚病毒核心颗粒的解体和病毒DNA进入细胞核的机制尚未被理解，我们现在报告的识别类似的丝氨酸或苏氨酸脯氨酸激酶识别位点的核心蛋白中的一个位置，这是需要为核心多肽组装成衣壳的序列基序。使用鸭肝炎B病毒，我们证明了在这个序列基序的突变可以对RNA包装，DNA复制和核心蛋白的稳定性产生深远的影响。此外，我们发现了一个突变体的条件表型依赖于用于病毒复制的细胞类型。我们的研究结果支持这一假设预测模体在病毒衣壳的组装和拆卸中发挥作用。
Hepadnaviruses are enveloped viruses, each with a DNA genome packaged in an icosahedral nucleocapsid, which is the site of viral DNA synthesis. In the presence of envelope proteins, DNA containing nucleocapsids are assembled into virions and secreted, but in the absence of these proteins, nucleocapsids deliver viral DNA into the cell nucleus. Presumably, this step is identical to the delivery of viral DNA during the initiation of an infection. Unfortunately, the mechanisms triggering the disintegration of subviral core particles and delivery of viral DNA into the nucleus are not yet understood, We now report the identification of a sequence motif resembling a serine- or threonine-proline kinase recognition site in the core protein at a location that is required for the assembly of core polypeptides into capsids. Using duck hepatitis B virus, we demonstrated that mutations at this sequence motif can have profound consequences for RNA packaging, DNA replication, and core protein stability. Furthermore, we found a mutant with a conditional phenotype that depended on the cell type used for virus replication. Our results support the hypothesis predicting that this motif plays a role in assembly and disassembly of viral capsids.