Kaposi's sarcoma-associated herpesvirus LANA hitches a ride on the chromosome
Kaposi's sarcoma-associated herpesvirus LANA hitches a ride on the chromosome
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DOI：
10.4161/cc.5.10.2768
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发表时间：
2006-05-15
期刊：
影响因子：
4.3
通讯作者：
Kaye, Kenneth M.
中科院分区：
文献类型：
--
作者：
Barbera, Andrew J.;Chodaparambil, Jayanth V.;Kaye, Kenneth M.
卡波西肉瘤相关疱疹病毒（KSHV）潜伏感染肿瘤细胞，并在卡波西肉瘤、原发性渗出性淋巴瘤和多中心Castleman病中起病因作用。在快速分裂的细胞中存活取决于一系列精心安排的事件。病毒基因组或附加体必须与细胞遗传物质一起复制，然后有效地分离到后代细胞核中。KSHV通过其潜伏相关核抗原（拉娜）实现这一点，LANA同时结合病毒DNA和有丝分裂染色体以有效地分配附加体。拉娜的N-末端区域已被证明对于KSHV DNA的有效复制和与有丝分裂染色体的连接是必不可少的。拉娜附着在宿主染色体上的确切机制一直是一个积极研究的领域。我们最近报道，这种关联是由染色质组分组蛋白H2 A和H2 B介导的。在体内和体外证明了拉娜与这些蛋白质之间的结合，并且使用H2 A-H2 B耗尽系统证明了它们在拉娜的染色体结合中的中心作用。此外，我们提供了一个结构描述的相互作用的拉娜的N-末端染色体关联区与核小体使用X-射线晶体学。我们的数据提供了进一步深入了解KSHV潜伏期的机制，也揭示了一个新的概念，作为其他蛋白质的对接站点的核小体的作用。
Kaposi's sarcoma-associated herpesvirus (KSHV) latently infects tumor cells and has an etiologic role in Kaposi's sarcoma, primary effusion lymphoma, and multicentric Castleman's disease. Survival in rapidly dividing cells depends on a carefully orchestrated chain of events. The viral genome, or episome, must replicate in concert with cellular genetic material, and then efficiently segregate to progeny nuclei. KSHV achieves this through its latency associated nuclear antigen (LANA), which simultaneously binds to viral DNA and mitotic chromosomes to efficiently partition episomes. LANA's N-terminal region has been shown to be essential for efficient KSHV DNA replication and tethering to mitotic chromosomes. The precise mechanism by which LANA attaches to host chromosomes has been an area of active investigation. We recently reported that this association is mediated by the chromatin components histones H2A and H2B. Binding between LANA and these proteins was demonstrated in vivo and in vitro, and use of an H2A-H2B depleted system demonstrated their central role in LANA's chromosome binding. Further, we provided a structural description of the interaction of LANA's N-terminal chromosome association region with the nucleosome using x-ray crystallography. Our data offer further insight into the mechanism of KSHV latency, and also reveal a new concept for a role of the nucleosome as a docking site for other proteins.