卡波济肉瘤是AIDS患者中最常见的恶性肿瘤。由于其病原体卡波济肉瘤相关疱疹病毒（KSHV）能在宿主细胞内建立有效的潜伏感染而无法从体内清除。在普通人群中，KSHV的感染率约为5%。KSHV维持潜伏感染的机制是该研究领域的热点问题。
2009年11月，国际权威病毒学杂志Journal of virology在线发表了上海巴斯德研究所蓝柯研究组关于KSHV潜伏感染机制研究的最新成果。研究人员通过酵母双杂交方法发现细胞协同抑制因子TLE2与KSHV周期调控开关分子RTA间的相互作用。TLE2能够对细胞内RTA水平改变做出应答，通过结合RTA以抑制RTA的转录激活作用，有效控制KSHV裂解期基因表达水平和病毒粒子的释放。进一步研究发现，TLE2能够置换与RTA结合的转录激活子，募集转录抑制复合体，从而实现对RTA转录激活作用的抑制。
该研究首次报道了TLE2这种新的RTA 结合蛋白，并揭示宿主细胞在KSHV潜伏感染维持中发挥了重要作用，为进一步阐明KSHV潜伏感染机制和针对KSHV持续感染的临床药物筛选提供线索。
该项研究是在蓝柯研究员指导下，由博士研究生何之恒、刘云华、梁德光、王卓等完成的。
该研究得到国家自然科学基金、中国科学院“百人计划”和赛诺菲-安万特-中科院上海生命科学研究院优秀青年人才基金项目的资助。（生物谷Bioon.com）
Figure. GST binding assay, co-immunoprecipitation and immunofluorescence indicate that TLE2 interacts with RTA in vitro and in vivo
生物谷推荐原始出处：
J. Virol. doi:10.1128/JVI.01984-09
Cellular corepressor TLE2 inhibits replication-and-transcription-activator-mediated transactivation and lytic reactivation of Kaposi's sarcoma-associated herpesvirus
Zhiheng He, Yunhua Liu, Deguang Liang, Zhuo Wang, Erle S. Robertson, and Ke Lan*
Key Laboratory of Molecular Virology and Immunology, Institute Pasteur of Shanghai, Shanghai institutes for biological sciences, Chinese Academy of Sciences, 225 South Chongqing Road, Shanghai 200025, The People's Republic of China; Department of Microbiology and The Abramson Comprehensive Cancer Center, University of Pennsylvania Medical School, 201E Johnson Pavilion, 3610 Hamilton Walk, Philadelphia, PA 19104, USA
Replication and transcription activator (RTA) encoded by ORF50 of Kaposi's sarcoma-associated herpesvirus (KSHV) is essential and sufficient to initiate lytic reactivation. RTA activates its target genes through direct binding with high affinity to its responsive elements or interaction with cellular factors, such as RBP-J, Ap-1, C/EBP- and Oct-1. In this study, we identified transducin-like enhancer of split 2 (TLE2) as a novel RTA binding protein by using yeast two hybrid screening of a human spleen cDNA library. The interaction between TLE2 and RTA was confirmed by GST binding and co-immunoprecipitation assays. Immunofluorescence analysis showed that TLE2 and RTA were co-localized in the same nuclear compartment in KSHV-infected cells. This interaction recruited TLE2 to RTA bound to its recognition sites on DNA, and repressed RTA auto-activation and transactivation activity. Moreover, TLE2 also inhibited the induction of lytic replication and virion production driven by RTA. We further showed that the Q, SP and WDR domains of TLE2 and the Pro-rich domain of RTA were essential for this interaction. RBP-J has been shown previously to bind to the same Pro-rich domain of RTA, and this binding can be subject to competition by TLE2. In addition, TLE2 can form a complex with RTA to access the cognate DNA sequence of RRE (RTA responsive element) at different promoters. Intriguingly, the transcription level of TLE2 could be upregulated by RTA during the lytic reactivation process. In conclusion, we identified a new RTA binding protein, TLE2, and demonstrated that TLE2 inhibited replication and transactivation mediated by RTA. This provides another potentially important mechanism for maintenance of KSHV viral latency through interaction with a host protein.
