近日，国际著名病毒学杂志Journal of Virology在线刊登了中科院上海巴斯德研究所蓝柯研究组的最新研究成果“LANA Carboxyl Terminal Amino Acids 1052 to 1082 Interact with RBP-Jκ and are Responsible for LANA-Mediated RTA Repression ，”，文章中，研究者关于卡波氏肉瘤病毒（KSHV）潜伏感染基因表达调控机制的最新研究成果。
KSHV属于gamma-2型人类疱疹病毒，是一种重要的人类肿瘤病毒，它可以引起卡波氏肉瘤(KS)、原发渗出性淋巴瘤(PEL)、多中心性卡斯特曼病(MCD)等数种恶性肿瘤，其中KS是AIDS患者中最常见的恶性肿瘤。KSHV在感染宿主后能建立长期潜伏感染，只有在特定的刺激下才会进行裂解复制。KSHV在体内建立潜伏感染的机制一直是领域内的研究热点之一。
为深入理解其感染调控机制，博士研究生金毅等在蓝柯研究员的指导下通过一系列生化实验，确定了病毒粒子携带的LANA蛋白与宿主转录因子RBP-Jκ 相互结合的最小作用区域，并且对此区域中氨基酸的组成和二级结构进行了分析。通过体外重构KSHV缺失LANA的病毒（Bac36△LANA），研究人员发现，缺失这段最小作用区域的LANA突变体与野生型LANA相比，无法有效抑制病毒RTA蛋白的转录，进一步证明了LANA与RBP-Jκ的结合对于病毒维持潜伏感染是十分重要的（如图），提示宿主转录因子RBP-Jκ在KSHV生命周期中扮演的重要角色，为发展新型抗KSHV感染的治疗手段提供了线索。
该研究得到国家科技部973计划、国家自然科学基金、中国科学院“百人计划” 等项目的资助。（生物谷Bioon.com）
doi:10.1128/JVI.06788-11JVI.06788-11
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LANA Carboxyl Terminal Amino Acids 1052 to 1082 Interact with RBP-Jκ and are Responsible for LANA-Mediated RTA Repression
Yi Jin1, Zhiheng He1, Deguang Liang1, Quanzhi Zhang1, Hongxing Zhang1, Qiang Deng1, Erle S. Robertson2,* and Ke Lan1,*
Kaposi's sarcoma-associated herpesvirus (KSHV), also known as human herpesvirus 8, is closely associated with several malignancies, including Kaposi's sarcoma, primary effusion lymphoma and multicentric Castleman's disease. KSHV can establish lifelong latency in the host, but the mechanism is not fully understood. Previous studies have proposed a feedback model in which the viral replication and transcription activator (RTA) can induce the expression of the latency associated nuclear antigen (LANA) during early infection. LANA in turn represses transcription and RTA function to establish and maintain KSHV latency. The interaction between LANA and the recombination signal sequence binding protein Jκ (RBP-Jκ, also called CSL), a major transcriptional repressor of the Notch signaling pathway, is essential for RTA repression. In the present study, we show that the LANA carboxyl terminal amino acids 1052 to 1082 were responsible for LANA interaction with RBP-Jκ. The secondary structure of LANA carboxyl terminus resembled the RBP-Jκ-associated module (RAM) of Notch receptor. Furthermore, deletion of the LANA 1052 to 1082 region resulted in aberrant expression of RTA, leading to elevated viral lytic replication. For the first time, we dissected a conserved RBP-Jκ binding domain in LANA and demonstrated that this domain was indispensible for LANA-mediated repression of KSHV lytic genes, thus helping the virus maintain latency and control viral reactivation.
