In vivo dynamics of EBNA1-oriP interaction during latent and lytic replication of Epstein-Barr virus
In vivo dynamics of EBNA1-oriP interaction during latent and lytic replication of Epstein-Barr virus
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DOI：
10.1074/jbc.m405911200
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发表时间：
2004-12-24
影响因子：
4.8
通讯作者：
Tsurumi, T
中科院分区：
文献类型：
--
作者：
Daikoku, T;Kudoh, A;Tsurumi, T
eb病毒（EBV）核抗原1 （EBNA1）在eb病毒复制潜伏期维持病毒基因组DNA是必需的，但在诱导病毒生产复制后继续合成。一项EBV全基因组染色质免疫沉淀试验显示，EBNA1在潜伏感染和裂解感染期间持续结合EBV基因组的oriP。尽管EBNA1的总水平在后者中被证明是恒定的，但随着裂解感染的进行，orp结合形式的水平增加。EBV产生性DNA复制发生在细胞核的离散位点，称为复制区室，病毒复制蛋白聚集在那里。共聚焦激光显微镜分析显示，EBNA1在感染潜伏期广泛分布在细胞核中，呈细点状分布，但在裂解复制诱导后，该蛋白重新分布到病毒复制区室中，并定位为区室内部或附近的不同点。考虑到这些发现，eb病毒基因组的oriP区域可能被EBNA1组织成复制结构域，为裂解复制和转录建立脚手架。
The Epstein-Barr virus (EBV) nuclear antigen 1 (EBNA1) is required for maintenance of the viral genome DNA during the latent phase of EBV replication but continues to be synthesized after the induction of viral productive replication. An EBV genome-wide chromatin immunoprecipitation assay revealed that EBNA1 constantly binds to oriP of the EBV genome during not only latent but also lytic infection. Although the total levels of EBNA1 proved constant throughout the latter, the levels of the oriP-bound form were increased as lytic infection proceeded. EBV productive DNA replication occurs at discrete sites in nuclei, called replication compartments, where viral replication proteins are clustered. Confocal laser microscopic analyses revealed that whereas EBNA1 was distributed broadly in nuclei as fine punctate dots during the latent phase of infection, the protein became redistributed to the viral replication compartments and localized as distinct spots within and/or nearby the compartments after the induction of lytic replication. Taking these findings into consideration, oriP regions of the EBV genome might be organized by EBNA1 into replication domains that may set up scaffolding for lytic replication and transcription.