ACTIVATION OF CD21 AND CD 23

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。eb病毒（EBV） EBNA2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相互作用被招募到它们的应答元件上。特别是，RTA和EBNA2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CD21和CD23a的表达至关重要。在这里，我们证明了与EBV EBNA2一样，KSHV RTA分别通过CD21的第一个内含子和CD23a核心启动子中的RBP-Jk结合位点强烈诱导CD21和CD23a的表达。然而，与EBV EBNA2改变免疫球蛋白mu （Igmu）和c-myc基因表达不同，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诱导的EBV受体CD21糖蛋白的表达有效地促进了EBV感染。此外，rta诱导的CD23糖蛋白发生蛋白水解，在B淋巴细胞和kshv感染的原发积液淋巴细胞中产生可溶性CD23 （sCD23）分子。然后sCD23刺激人原代淋巴细胞。这些结果表明细胞CD21和CD23a是B淋巴性γ疱疹病毒的共同靶点，KSHV RTA调节rbp - jk介导的细胞基因表达，最终为病毒在受感染宿主中的繁殖提供了有利的环境。

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.