Activation of CD21 and CD23 gene expression by Kaposi's sarcoma-associated herpesvirus RTA
Activation of CD21 and CD23 gene expression by Kaposi's sarcoma-associated herpesvirus RTA
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DOI：
10.1128/jvi.79.8.4651-4663.2005
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发表时间：
2005-04-01
影响因子：
5.4
通讯作者：
Jung, JU
中科院分区：
文献类型：
--
作者：
Chang, H;Gwack, Y;Jung, JU
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-J kappa相互作用被招募到它们的反应元件。特别是，RTA和EBNA2与RBP-J kappa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第一内含子上的RBP-J kappa结合位点和CD23a核心启动子中的RBP-J kappa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u(Ig U)和c-myc基因表达不同，RTA不影响Ig u和c-myc的表达，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-J kappa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。
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-J kappa. In particular, RTA and EBNA2 interactions with RBP-J kappa 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-J kappa binding sites in the first intron of CD21 and in the CD23a core promoter, respectively. However, unlike EBV EBNA2, which alters immunoglobulin mu (Ig mu) and c-myc gene expression, RTA did not affect Ig mu 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-J kappa-mediated cellular gene expression, which ultimately provides a favorable milieu for viral reproduction in the infected host.