The mechanism of genome maintenance and transcriptional regulation in latent HCMV infection

潜伏性HCMV感染中基因组维持和转录调控机制

• 批准号: 17590429
• 负责人: ISOMURA Hiroki
• 金额: $ 2.3万
• 依托单位: Aichi Cancer Center Research Institute
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2005
• 资助国家: 日本
• 起止时间: 2005 至 2006
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-17590429/
• 关键词: Cytomegalovirus; Transcriptional regulation; 遺伝子制御; ヒトサイトメガロウイルス; エンハンサー; Sp1; 前初期遺伝子; BAC

We previous demonstrated that the major immediate early (MIE) proximal enhancer containing one GC box and the TATA box containing promoter are minimal elements required for transcription and viral replication (H.Isomura et al. J.Virol. 78:12788, 2004). Here we report that Electrophoretic mobility shift assays (EMSAs) detected binding of Sp1 and Sp3 transcription factors to the GC boxes located at approximately-55 and -75 relative to the transcription start site (+1). Reporter gene experiments showed that both of the Sp1/Sp3 binding sites have a positive and synergistic effect on the HCMV MIE promoter. After infection, the level of Sp1 increased while Sp3 remain constant. There was little to no change in MIE transcription or viral replication for recombinant viruses with one or the other Sp1/Sp3 binding site mutated. In contrast, mutation of both Sp1/Sp3 binding sites caused inefficient MIE transcription and viral replication. These data indicate that the Sp1/3 binding sites have a significant role in HCMV replication.

我们先前证明，含有一个GC盒的主要立即早期（MIE）近端增强子和含有启动子的TATA盒是转录和病毒复制所需的最小元件（H.Isomura等，J.Virol. 78：12788，2004）。在这里，我们报告，电泳迁移率变动分析（EMSA）检测到的Sp1和Sp3转录因子的GC盒位于约-55和-75相对于转录起始位点（+1）的结合。报告基因实验表明，这两个Sp1/Sp3结合位点对HCMV MIE启动子具有积极的协同作用。感染后，Sp1水平升高，而Sp3水平保持不变。对于一个或另一个Sp1/Sp3结合位点突变的重组病毒，MIE转录或病毒复制几乎没有变化。相反，两个Sp1/Sp3结合位点的突变导致MIE转录和病毒复制效率低下。这些数据表明Sp1/3结合位点在HCMV复制中具有重要作用。

项目成果

Phosphorylation of MCM4 at sites inactivating DNA helicase activity of the MCM4-MCM6-MCM7 complex during Epstein-Barr virus productive replication

• DOI: 10.1128/jvi.00678-06
• 发表时间: 2006-10-01
• 期刊: JOURNAL OF VIROLOGY
• 影响因子: 5.4
• 作者: Kudoh, Ayumi;Daikoku, Tohru;Tsurumi, Tatsuya
• 通讯作者: Tsurumi, Tatsuya

Epstein-Barr virus lytic replication elicits ATM checkpoint signal transduction while providing an S-phase-like cellular environment. J. Biol. Chem., 280 : 8156-8163, 2005

Epstein-Barr 病毒裂解复制引发 ATM 检查点信号转导，同时提供类似 S 期的细胞环境。

• 发表时间: 2005
• 期刊: J. Biol. Chem. 280
• 作者: Kudoh A.;Fujita M.;Zhan L.;Shirata N.;Daikoku T.;Sugaya Y.;Isomura H.;Nishiyama Y.;Tsurumi T
• 通讯作者: Tsurumi T

Postreplicative mismatch repair factors are recruited to Epstein-Barr virus replication compartments

• DOI: 10.1074/jbc.m510314200
• 发表时间: 2006-04-21
• 期刊: JOURNAL OF BIOLOGICAL CHEMISTRY
• 影响因子: 4.8
• 作者: Daikoku, T;Kudoh, A;Tsurumi, T
• 通讯作者: Tsurumi, T

Architecture of replication compartments formed during Epstein-Barr virus lytic replication

• DOI: 10.1128/jvi.79.6.3409-3418.2005
• 发表时间: 2005-03-01
• 期刊: JOURNAL OF VIROLOGY
• 影响因子: 5.4
• 作者: Daikoku, T;Kudoh, A;Tsurumi, T
• 通讯作者: Tsurumi, T

Activation of Ataxia Telangiectasia-mutated DNA Damage Checkpoint Signal Transduction Elicited by Herpes Simplex Virus Infection*

• DOI: 10.1074/jbc.m500976200
• 发表时间: 2005-08
• 期刊: Journal of Biological Chemistry
• 影响因子: 4.8
• 作者: Noriko Shirata;A. Kudoh;T. Daikoku;Yasutoshi Tatsumi;M. Fujita;T. Kiyono;Y. Sugaya;Hiroki Isomura;K. Ishizaki;T. Tsurumi