Kaposi's Sarcoma-Associated Herpesvirus-Encoded LANA Interacts with Host KAP1 To Facilitate Establishment of Viral Latency
Kaposi's Sarcoma-Associated Herpesvirus-Encoded LANA Interacts with Host KAP1 To Facilitate Establishment of Viral Latency
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卡波西肉瘤相关疱疹病毒编码的 LANA 与宿主 KAP1 相互作用，促进病毒潜伏期的建立
DOI：
10.1128/jvi.00596-14
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发表时间：
2014-04
影响因子：
5.4
通讯作者：
Lan Ke
中科院分区：
文献类型：
--
作者：
Sun Rui;Liang Deguang;Gao Yuan;Lan Ke
摘要卡波西肉瘤相关疱疹病毒（KSHV）在其生命周期中通常表现为两个不同的阶段，默认潜伏期和裂解期。在KSHV初次感染的早期，有一个短暂的裂解基因表达期。在裂解基因表达的关闭过程中涉及的因素很少确定。研究表明，KSHV编码的潜伏相关核抗原（拉娜）在病毒潜伏期的建立中起重要作用。在筛选中，我们鉴定了一种与拉娜结合的宿主蛋白，Krüppel相关盒结构域相关蛋白1（KAP 1）。我们在体内和体外验证了拉娜和KAP 1之间的相互作用，以及它们在细胞核中的共定位。我们绘制出拉娜与KAP 1的N-和C-末端结构域相互作用。基于LANA-KAP 1相互作用界面的确定，我们证明了拉娜将KAP 1募集到KSHV基因组的RTA启动子区。我们发现KAP 1参与了拉娜的转录抑制。我们通过染色质免疫沉淀测序（ChIP-seq）发现拉娜和KAP 1在整个KSHV基因组上存在多个共占据位点，并证明LANA募集的KAP 1在KSHV初次感染早期裂解基因表达的关闭中起关键作用。总之，我们的数据表明，拉娜与KAP 1相互作用，抑制裂解基因的表达，以促进建立KSHV潜伏期。重要意义我们的研究揭示了拉娜在KSHV初次感染过程中的转录抑制机制，为KSHV潜伏期建立过程提供了新的见解。
ABSTRACT Kaposi's sarcoma-associated herpesvirus (KSHV) typically displays two different phases in its life cycle, the default latent phase and the lytic phase. There is a short period of lytic gene expression in the early stage of KSHV primary infection. The factors involved in the shutdown process of lytic gene expression are poorly identified. It has been shown that the latency-associated nuclear antigen (LANA) encoded by KSHV plays an important role in the establishment of viral latency. In screening, we identified a host protein, Krüppel-associated box domain-associated protein 1 (KAP1), that bound to LANA. We validated the interaction between LANA and KAP1 in vivo and in vitro, as well as their colocalization in the nucleus. We mapped out that LANA interacted with both the N- and C-terminal domains of KAP1. Based on the interface of LANA-KAP1 interaction determined, we proved that LANA recruited KAP1 to the RTA promoter region of the KSHV genome. We revealed that KAP1 was involved in transcriptional repression by LANA. We found multiple cooccupation sites of LANA and KAP1 on the whole KSHV genome by chromatin immunoprecipitation for sequencing (ChIP-seq) and demonstrated that LANA-recruited KAP1 played a critical role in the shutdown of lytic gene expression during the early stage of KSHV primary infection. Taken together, our data suggest that LANA interacts with KAP1 and represses lytic gene expression to facilitate the establishment of KSHV latency. IMPORTANCE Our study revealed the mechanism of transcriptional repression by LANA during KSHV primary infection, providing new insights into the process of KSHV latency establishment.
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影响因子：
5.4
作者：
Ye, FC;Zhou, FC;Gao, SJ
通讯作者：
Gao, SJ
影响因子：
48
作者：
Langmead, Ben;Salzberg, Steven L.
通讯作者：
Salzberg, Steven L.
影响因子：
6.7
作者：
Hellert J;Weidner-Glunde M;Krausze J;Richter U;Adler H;Fedorov R;Pietrek M;Rückert J;Ritter C;Schulz TF;Lührs T
通讯作者：
Lührs T
Kaposi肉瘤相关的疱疹病毒调节蛋白的翻译后修饰 - SUMO和KSHV。
影响因子：
5.2
作者：
Campbell M;Izumiya Y
通讯作者：
Izumiya Y
Kruppel相关的盒子结构域相关蛋白-1作为Kaposi肉瘤相关的疱疹病毒的潜伏期调节剂及其通过病毒蛋白激酶的调节。
影响因子：
11.2
作者：
Chang PC;Fitzgerald LD;Van Geelen A;Izumiya Y;Ellison TJ;Wang DH;Ann DK;Luciw PA;Kung HJ
通讯作者：
Kung HJ