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.

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。子项目和研究者（PI）可能从另一个NIH来源获得主要资金，因此可以在其他CRISP条目中表示。所列机构为中心，不一定是研究者所在机构。EB病毒（EBV）EBNA 2和卡波西肉瘤相关疱疹病毒（KSHV）复制和转录激活因子（RTA）通过与Notch介导的转录因子RBP-Jk相互作用被招募到其应答元件。特别是，RTA和EBNA 2与RBP-Jk的相互作用分别对KSHV的裂解复制和B细胞活化标志物CD 21和CD 23 a的表达至关重要。在这里，我们证明，像EBV EBNA 2，KSHV RTA强烈诱导CD 21和CD 23 a的表达，通过RBP-Jk结合位点的第一个内含子的CD 21和CD 23 a的核心启动子，分别。然而，与改变免疫球蛋白mu（Igmu）和c-myc基因表达的EBV EBNA 2不同，RTA不影响Igmu和c-myc表达，表明KSHV RTA以与EBV EBNA 2类似但不同的方式靶向Notch信号转导途径。此外，RTA诱导的CD 21糖蛋白（EBV受体）的表达有效地促进了EBV感染。此外，RTA诱导的CD 23糖蛋白发生蛋白水解，并在B淋巴细胞和KSHV感染的原发性渗出液淋巴细胞中产生可溶性CD 23（sCD 23）分子。然后sCD 23刺激原代人淋巴细胞。这些结果表明，细胞CD 21和CD 23 a是B嗜淋巴细胞γ疱疹病毒的常见靶标，并且KSHV RTA调节RBP-Jk介导的细胞基因表达，这最终为感染宿主中的病毒繁殖提供了有利的环境。