卡波氏肉瘤相关疱疹病毒(KSHV)是卡波氏肉瘤等艾滋病常见肿瘤的病原。重组信号序列结合蛋白J kappa (RBPJ)与复制与转录激活因子(RTA)结合促进KSHV裂解复制，与潜伏相关核抗原(LANA)结合则维持潜伏感染。但RTA与LANA对RBPJ表达的影响，以及RBPJ在KSHV复制状态转换中的作用尚不清楚。我们前期研究结果提示RTA和LANA通过共调控let-7a/RBPJ信号，RBPJ表达水平可能是控制KSHV复制状态转换的决定因素。本项目将首先研究RTA、LANA调控let-7a/RBPJ的机制，然后分析RTA与LANA相对量对let-7a/RBPJ信号的影响，以及let-7a/RBPJ在RTA与LANA表达调控中的作用，最后探讨let-7a/RBPJ在KSHV复制状态转换中的作用。本研究将为深入理解KSHV复制调控机制及相关疾病的防治提供新的理论支持。

Kaposi’s sarcoma-associated herpesvirus (KSHV) is associated with Kaposi’s sarcoma (KS) and other acquired immunodeficiency syndromes related tumors. KSHV latent infection and lytic replication and the continued infection of new cells are therefore likely to be essential for the maintenance of the population of infected cells and development of viral pathogenesis. The latency-associated nuclear antigen (LANA) and replication and transcription activator (RTA) binding with the recombination signal binding protein for immunoglobulin kappa J region (RBPJ), respectively, which to facilitate lytic replication or latent infection. However, the relationship between expression regulation of LANA, RTA and RBPJ is not clear. Previously, we found LANA increased let-7a while RTA decreases let-7a expression, and RBPJ directly targeted by let-7a. We hypothesized that LANA and RTA co-regulating the let-7a/RBPJ signaling to control KSHV replication status switching. The let-7a/RBPJ is the key signaling pathway of regulating KSHV latent establish, maintenance, and switch to lytic replication. In this proposal, we will explore: the mechanisms of regulating let-7a/RBPJ signaling by RTA or LANA; the effects of KSHV replication status and different RTA and LANA ratio on let-7a/RBPJ signaling; and, the role of let-7a/RBPJ on regulating LANA and RTA expression; the effect of let-7a/RBPJ signaling on KSHV replication status switching. Our data will be useful to further elucidate the mechanism KSHV replication.