Transcriptional regulation of herpesviruses dependent on the viral DNA replication

疱疹病毒的转录调控依赖于病毒 DNA 复制

• 批准号: 21590524
• 负责人: ISOMURA Hiroki
• 金额: $ 3万
• 依托单位: Gunma University (2011)Aichi Cancer Center Research Institute (2009-2010)
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2009
• 资助国家: 日本
• 起止时间: 2009 至 2011
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-21590524/
• 关键词: ヒトサイトメガロウイルス; 後期遺伝子; 転写制御; DNA複製

The regulation of human cytomegalovirus (HCMV) late gene expression by viral proteins is poorly understood. HCMV open reading frames (ORFs) UL79,-87, and-95 encode proteins with homology to late gene transcription factors of murine gammaherpesvirus 68 ORFs 18, 24, and 34, respectively. To determine whether these HCMV proteins are also essential for late gene transcription of a betaherpesvirus, we mutated HCMV ORFs UL79,-87, and-95. Cells were infected with the recombinant viruses at high and low multiplicities of infection (MOIs). While viral DNA was detected with the recombinant viruses, infectious virus was not detected unless the wild-type viral proteins were expressed in trans. At a high MOI, mutation of ORF UL79,-87, or-95 had no effect on the level of major immediate-early (MIE) gene expression or viral DNA replication, but late viral gene expression from the UL44,-75, and-99 ORFs was not detected. At a low MOI, preexpression of UL79 or-87, but not UL95, in human fibroblast cells negatively affected the level of MIE viral gene expression and viral DNA replication. The products of ORFs UL79,-87, and-95 were expressed as early viral proteins and recruited to prereplication complexes (pre-RCs), along with UL44, before the initiation of viral DNA replication. All three HCMV ORFs are indispensable for late viral gene expression and viral growth.

病毒蛋白对人巨细胞病毒（HCMV）晚期基因表达的调控作用尚不清楚。HCMV开放阅读框（ORFs） UL79、-87和95编码的蛋白分别与鼠γ疱疹病毒68 ORFs 18、24和34的晚期基因转录因子同源。为了确定这些HCMV蛋白是否也是β疱疹病毒晚期基因转录所必需的，我们突变了HCMV ORFs UL79，-87和95。重组病毒在高、低感染多重度（MOIs）下感染细胞。在重组病毒中检测到病毒DNA，除非以反式表达野生型病毒蛋白，否则无法检测到感染性病毒。在高MOI下，ORF UL79、-87、或95的突变对主要即刻早期（MIE）基因表达水平或病毒DNA复制没有影响，但未检测到UL44、-75和99 ORF的晚期病毒基因表达。在低MOI条件下，人成纤维细胞中UL79或ul87的预表达（而非UL95）对MIE病毒基因表达水平和病毒DNA复制产生负向影响。ORFs的产物UL79，-87和95作为早期病毒蛋白表达，并在病毒DNA复制开始之前与UL44一起招募到复制前复合物（pre- rc）。这三种HCMV orf对于病毒晚期基因表达和病毒生长都是必不可少的。

项目成果

ヒトサイトメガロウイルス.松島綱治編,分子予防環境医学

人类巨细胞病毒，松岛纲治主编，分子预防环境医学。

• 发表时间: 2010
• 作者: Kitamura;S.;Ode;H.;and Iwatani;Y;磯村寛樹
• 通讯作者: 磯村寛樹

The human cytomegalovirus UL76 gene regulates the level of expression of the UL77 gene.

• DOI: 10.1371/journal.pone.0011901
• 发表时间: 2010-07-30
• 期刊: PloS one
• 影响因子: 3.7
• 作者: Isomura H;Stinski MF;Murata T;Nakayama S;Chiba S;Akatsuka Y;Kanda T;Tsurumi T
• 通讯作者: Tsurumi T

ヒトの体内では増殖不可能な弱毒性ヒトサイトメガロウィルス株の作成

创建不能在人体内增殖的弱毒力人类巨细胞病毒株

• 发表时间: 2011

Human Cytomegalovirus Late Transactivators Recruited to the Replication Compartments

人类巨细胞病毒晚期反式激活子被招募到复制室

• 发表时间: 2010
• 作者: Isomura H.;Stinski M.F.;Murata T.;Kanda T.;Tsurumi T
• 通讯作者: Tsurumi T

DNA polymerase processivity factor of human cytomegalovirus may be a key molecule for molecular coupling of viral DNA replication to transcription. Edited by Jelena Kusic, DNA Replication/Book 2, ISBN

人巨细胞病毒的DNA聚合酶持续合成因子可能是病毒DNA复制与转录分子偶联的关键分子。

• 作者: Kitamura;S.;Ode;H.;and Iwatani;Y;磯村寛樹;Isomura H
• 通讯作者: Isomura H