KAPOSI?S SARCOMA-ASSOCIATED HERPESVIRUS GENE EXPRESSION

卡波西肉瘤相关疱疹病毒基因表达

• 批准号: 7349564
• 负责人: HEESON CHANG
• 金额: $ 6.63万
• 依托单位: HARVARD MEDICAL SCHOOL
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-05-01 至 2007-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7349564
• 关键词: KAPOSI; SARCOMA; ASSOCIATED; HERPESVIRUS; GENE

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Kaposi's sarcom-associated herpesvirus (KSHV) RTA transcription factor is recruited to its responsive elements through interaction with a Notch-mediated transcription factor, RBP-Jk, indicating that RTA mimics cellular Notch signal transduction to activate viral lytic gene expression. To test whether cellular Notch signal transduction and RTA are functionally exchangeable for viral gene expression, human Notch intracellular (NIC) domain that constitutively activates RBP-Jk transcription factor activity was expressed in KSHV-infected primary effusion lymphoma BCBL1 cells (TRExBCBL1-HNIC) in a tetracycline-inducible manner. Gene expression profiling showed that like RTA, hNIC robustly induced expression of a number of viral genes, including viral interleukin 6 (vIL-6), K3 and K5. Unlike RTA, however, hNIC was not capable of evoking the full repertoire of lytic viral gene expression and thereby lytic replication. To further understand the role of Notch signal transduction in KSHV gene expression, vIL-6 growth factor and K5 immune modulator genes were selected for detailed analysis. Despite the presence of multiple RBP-Jk binding sites, hNIC targeted the specific RBP-Jk binding sites of vIL-6 and K5 promoter regions to regulate their gene expression. These results indicate that cellular Notch signal transduction not only is partially exchangeable with RTA in regard to activation of viral lytic gene expression, but also provides a novel expression profile of KSHV growth and immune deregulatory genes that is likely different from that of RTA-independent standard latency program as well as RTA-dependent lytic reproduction program.

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子弹和调查员（PI）可能已经从其他NIH来源获得了主要资金，因此可以在其他清晰的条目中代表。列出的机构适用于该中心，这不一定是调查员的机构。 Kaposi与肉瘤相关的疱疹病毒（KSHV）RTA转录因子通过与Notch介导的转录因子RBP-JK相互作用募集到其响应元件中，RBP-JK，表明RTA模拟了细胞置换notch信号转导能激活病毒裂解基因表达。为了测试细胞档位信号转导和RTA是否在功能上可以换成病毒基因表达，人口缺失（NIC）结构域构成激活RBP-JK转录因子活性在KSHV感染的原发性淋巴瘤BCBL1细胞中表达了RBP-JK转录因子活性。基因表达分析表明，像RTA一样，HNIC强诱导了许多病毒基因的表达，包括病毒白介素6（VIL-6），K3和K5。但是，与RTA不同，HNIC无法唤起裂解病毒基因表达的完整曲目，从而唤起了裂解的复制。为了进一步了解Notch信号转导在KSHV基因表达中的作用，选择了VIL-6生长因子和K5免疫调节剂基因进行详细分析。尽管存在多个RBP-JK结合位点，但HNIC还是针对VIL-6和K5启动子区域的特定RBP-JK结合位点，以调节其基因表达。这些结果表明，在病毒裂解基因表达的激活方面，细胞凹口信号转导不仅可以与RTA部分交换，而且还提供了KSHV生长和免疫输血基因的新颖表达概况，这些基因可能与RTA独立的标准延迟程序以及RTA依赖性Lytic lytic lytic Rodict Ropoduction的新表达能力。