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。 Epstein-Barr 病毒 (EBV) EBNA2 和卡波西肉瘤相关疱疹病毒 (KSHV) 复制和转录激活子 (RTA) 通过与 Notch 介导的转录因子 RBP-Jk 相互作用而被招募到其响应元件中。特别是，RTA 和 EBNA2 与 RBP-Jk 的相互作用对于 KSHV 的裂解性复制以及 B 细胞激活标记物 CD21 和 CD23a 的表达分别至关重要。在这里，我们证明，与 EBV EBNA2 一样，KSHV RTA 分别通过 CD21 第一个内含子和 CD23a 核心启动子中的 RBP-Jk 结合位点强烈诱导 CD21 和 CD23a 表达。然而，与改变免疫球蛋白 mu (Igmu) 和 c-myc 基因表达的 EBV EBNA2 不同，RTA 不影响 Igmu 和 c-myc 表达，表明 KSHV RTA 以类似于但又不同的方式靶向 Notch 信号转导通路。 EBV EBNA2。此外，RTA 诱导的 CD21 糖蛋白（EBV 受体）表达可有效促进 EBV 感染。此外，RTA 诱导的 CD23 糖蛋白经历蛋白水解，并在 B 淋巴细胞和 KSHV 感染的原代渗出淋巴细胞中产生可溶性 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 CD21 和 CD23a 是 B 淋巴细胞性伽马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，最终为感染宿主中的病毒繁殖提供有利的环境。