ACTIVATION OF CD21 AND CD 23

CD21 和 CD 23 的激活

• 批准号: 7349572
• 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/7349572
• 关键词: ACTIVATION; CD21; CD; 23

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. Epstein-Barr virus (EBV) EBNA2 and Kaposi's sarcoma-associated herpesvirus (KSHV) replication and transcription activator (RTA) are recruited to their responsive elements through interaction with a Notch-mediated transcription factor, RBP-Jk. In particular, RTA and EBNA2 interactions with RBP-Jk are essential for the lytic replication of KSHV and expression of B-cell activation markers CD21 and CD23a, respectively. Here, we demonstrate that like EBV EBNA2, KSHV RTA strongly induces CD21 and CD23a expression through RBP-Jk binding sites in the first intron of CD21 and in the CD23a core promoter, respectively. However, unlike EBV EBNA2, which alters immunoglobulin mu (Igmu) and c-myc gene expression, RTA did not affect Igmu and c-myc expression, indicating that KSHV RTA targets the Notch signal transduction pathway in a manner similar to but distinct from that of EBV EBNA2. Furthermore, RTA-induced expression of CD21 glycoprotein, which is an EBV receptor, efficiently facilitated EBV infection. In addition, RTA-induced CD23 glycoprotein underwent proteolysis and gave rise to soluble CD23 (sCD23) molecules in B lymphocytes and KSHV-infected primary effusion lymphocytes. sCD23 then stimulated primary human lymphocytes. These results demonstrate that cellular CD21 and CD23a are common targets for B lymphotropic gammaherpesviruses and that KSHV RTA regulates RBP-Jk-mediated cellular gene expression, which ultimately provides a favorable milieu for viral reproduction in the infected host.

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。Epstein-Barr病毒(EBV)EBNA2和Kaposi的肉瘤相关疱疹病毒(KSHV)复制和转录激活因子(RTA)通过与Notch介导的转录因子RBP-JK相互作用被招募到它们的反应元件。特别是，RTA和EBNA2与RBP-JK的相互作用对于KSHV的裂解复制和B细胞激活标记CD21和CD23a的表达分别是必不可少的。在这里，我们证明了与EBV EBNA2一样，KSHV RTA通过CD21第一内含子的RBP-JK结合位点和CD23a核心启动子的RBP-JK结合位点强烈诱导CD21和CD23a的表达。然而，与EBV EBNA2不同的是，RTA不影响IgMU和c-myc的表达，这表明KSHV RTA以与EBV EBNA2相似但不同的方式靶向Notch信号转导途径。此外，RTA诱导EBV受体CD21糖蛋白的表达有效地促进了EBV的感染。此外，RTA诱导的CD23糖蛋白在B淋巴细胞和KSHV感染的原发积液淋巴细胞中发生蛋白降解，产生可溶性CD23(SCD23)分子。然后，sCD23刺激原代人类淋巴细胞。这些结果表明，细胞内的CD21和CD23a是嗜B淋巴细胞的伽马疱疹病毒的共同靶点，而KSHV RTA调控RBP-JK介导的细胞基因表达，最终为病毒在感染宿主中的繁殖提供了有利的环境。