近日，國際著名病毒學雜志Journal of Virology在線刊登了中科院上海巴斯德研究所藍柯研究組的最新研究成果“LANA Carboxyl Terminal Amino Acids 1052 to 1082 Interact with RBP-Jκ and are Responsible for LANA-Mediated RTA Repression ,，”,，文章中，研究者關于卡波氏肉瘤病毒（KSHV）潛伏感染基因表達調(diào)控機制的最新研究成果,。
KSHV屬于gamma-2型人類皰疹病毒,，是一種重要的人類腫瘤病毒，它可以引起卡波氏肉瘤(KS),、原發(fā)滲出性淋巴瘤(PEL),、多中心性卡斯特曼病(MCD)等數(shù)種惡性腫瘤，其中KS是AIDS患者中最常見的惡性腫瘤,。KSHV在感染宿主后能建立長期潛伏感染,，只有在特定的刺激下才會進行裂解復制,。KSHV在體內(nèi)建立潛伏感染的機制一直是領域內(nèi)的研究熱點之一。
為深入理解其感染調(diào)控機制,，博士研究生金毅等在藍柯研究員的指導下通過一系列生化實驗,，確定了病毒粒子攜帶的LANA蛋白與宿主轉(zhuǎn)錄因子RBP-Jκ 相互結(jié)合的最小作用區(qū)域，并且對此區(qū)域中氨基酸的組成和二級結(jié)構(gòu)進行了分析,。通過體外重構(gòu)KSHV缺失LANA的病毒（Bac36△LANA）,，研究人員發(fā)現(xiàn)，缺失這段最小作用區(qū)域的LANA突變體與野生型LANA相比,，無法有效抑制病毒RTA蛋白的轉(zhuǎn)錄,，進一步證明了LANA與RBP-Jκ的結(jié)合對于病毒維持潛伏感染是十分重要的（如圖），提示宿主轉(zhuǎn)錄因子RBP-Jκ在KSHV生命周期中扮演的重要角色,，為發(fā)展新型抗KSHV感染的治療手段提供了線索,。
該研究得到國家科技部973計劃、國家自然科學基金,、中國科學院“百人計劃” 等項目的資助,。（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.
