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 资助的中心拨款提供的资源的众多研究子项目之一。子项目和研究者 (PI) 可能已从另一个 NIH 来源获得主要资金，因此可以在其他 CRISP 条目中出现。列出的机构是中心的机构，不一定是研究者的机构。卡波西肉瘤相关疱疹病毒 (KSHV) RTA 转录因子通过与 Notch 介导的转录因子 RBP-Jk 相互作用而被招募至其响应元件，表明 RTA 模拟细胞 Notch 信号转导以激活病毒裂解基因表达。为了测试细胞Notch信号转导和RTA是否可以在功能上互换病毒基因表达，在KSHV感染的原发性渗出性淋巴瘤BCBL1细胞（TRExBCBL1-HNIC）中表达了组成型激活RBP-Jk转录因子活性的人Notch胞内（NIC）结构域。四环素诱导方式。基因表达谱显示，与 RTA 一样，hNIC 强烈诱导许多病毒基因的表达，包括病毒白细胞介素 6 (vIL-6)、K3 和 K5。然而，与 RTA 不同的是，hNIC 无法激发裂解病毒基因表达的全部功能，从而引发裂解复制。为了进一步了解Notch信号转导在KSHV基因表达中的作用，选择vIL-6生长因子和K5免疫调节基因进行详细分析。尽管存在多个 RBP-Jk 结合位点，hNIC 仍靶向 vIL-6 和 K5 启动子区域的特定 RBP-Jk 结合位点来调节其基因表达。这些结果表明，细胞Notch信号转导不仅在激活病毒裂解基因表达方面与RTA部分可互换，而且还提供了KSHV生长和免疫失调基因的新表达谱，该表达谱可能与不依赖RTA的标准不同。潜伏期程序以及 RTA 依赖性裂解繁殖程序。