TLR7/8-TRAF6-IRF7调控KSHV病毒周期的分子机制

Kaposi's sarcoma is a locally invasive endothelial cells tumor , the pathogenesis is not completely clear. KSHV is the etiologic agent of Kaposi’s sarcoma,which infection is necessary for the development of KS,but not all KSHV infection can progress into ks. KSHV exhibits a biphasic life cycle consisting of a latent phase and a transient lytic reactivation phase, The lytic reactivation state is related to the occurrence of KS.Studies have confirmed that TLR7/8 can activate the KSHV virus from latency to lytic cycle, but the specific molecular mechanism is unknown.The study is designed respectively in human tissue (cancer tissue: AIDS-KS and classic KS) and cell model two aspects, using ( gene silencing, building expression recombinant plasmid, cell transfection) a variety of methods.Detect the expression of the key protein of TLR7/8-TRAF6-IRF7 signaling pathway in patients tumor tissue.Over-expression and gene silencing TRAF6 and IRF7 the target proteinof TLR7/8-TRAF6-IRF7 signaling pathway in vitro.Which intends to clarify the molecular mechanisms of TLR7/8-TRAF6-IRF7 regulate KSHV in latent phase and transient lytic reactivation phase, and the role played in apoptosis of the infection cells.This study will lay the foundation for finding new targets for clinical intervention.

卡波西肉瘤（KS）是一种具有局部侵袭性的内皮细胞肿瘤，发病机制未完全阐明，KSHV感染是KS发生的病原学基础，KS患者均感染KSHV，但感染KSHV并不一定发展为KS，KSHV 存在潜伏和裂解复制感染两种状态，裂解期与KS肿瘤的发生相关。已有研究证实：TLR7/8可激活KSHV病毒周期由潜伏期至裂解期，但具体分子机制未明。本研究拟分别从人体组织（癌组织:AIDS-KS和经典KS）、细胞模型两个方面，运用（基因沉默、构建过表达重组质粒、细胞转染）等多种方法，通过检测患者肿瘤组织中TLR7/8-TRAF6-IRF7信号通路关键蛋白的表达以及在体外细胞对TLR7/8信号通路中靶蛋白TRAF6和IRF7进行过表达和基因沉默，阐明TLR7/8-TRAF6-IRF7对KSHV病毒复制周期中潜伏与裂解复制感染状态的调节机制，以及对感染细胞凋亡的影响，为发现新的临床干预靶标奠定基础。