Kaposi's sarcoma-associated herpesvirus RTA activates the processivity factor ORF59 through interaction with RBP-Jkappa and a cis-acting RTA responsive element.
Kaposi's sarcoma-associated herpesvirus RTA activates the processivity factor ORF59 through interaction with RBP-Jkappa and a cis-acting RTA responsive element.
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卡波西肉瘤相关疱疹病毒 RTA 通过与 RBP-Jkappa 和顺式作用 RTA 反应元件相互作用，激活持续合成因子 ORF59。
DOI：
10.1016/j.virol.2008.08.011
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发表时间：
2008-10-25
期刊：
影响因子：
3.7
通讯作者：
Lan K
中科院分区：
文献类型：
--
作者：
Liu Y;Cao Y;Liang D;Gao Y;Xia T;Robertson ES;Lan K
Kaposi肉瘤相关疱疹病毒(KSHV/HHV8)在感染的宿主细胞中表现出两种生命模式，潜伏期和裂解再激活，这两种模式在病毒介导的致病过程中同样重要。在潜伏期，只有一小部分基因被表达。在特定条件下，KSHV可以进行裂解复制并产生病毒后代。一个由KSHV开放阅读框50编码的即刻早期基因RTA，已被证明在将病毒潜伏时间转换为裂解重新激活的过程中发挥关键作用。异源启动子RTA的过度表达足以驱动KSHV裂解复制，从而产生病毒后代。在目前的研究中，我们发现RTA可以激活ORF59的表达，ORF59编码在裂解再激活过程中DNA复制所必需的过程性因子。我们还表明，Rta通过与RBP-Jκ以及启动子内的顺式作用Rta反应元件相互作用来调节ORF59启动子。在KSHV感染细胞中，ORF59的上调是对RTA表达的直接反应。综上所述，我们的发现为解释RTA调节其下游基因ORF59的机制提供了新的证据，进一步加深了我们对KSHV裂解复制生物学的理解。
Kaposi’s sarcoma-associated herpesvirus (KSHV/HHV8) displays two life modes, latency and lytic reactivation in the infected host cells which are equally important for virus mediated pathogenesis. During latency only a small number of genes are expressed. Under specific conditions, KSHV can undergo lytic replication with the production of viral progeny. One immediate-early gene RTA, encoded by open reading frame 50 of KSHV, has been shown to play a critical role in switching the viral latency to lytic reactivation. Over-expression of RTA from a heterologous promoter is sufficient for driving KSHV lytic replication which results in production of viral progeny. In the present study, we show that RTA can activate the expression of the ORF59 which encodes the processivity factor essential for DNA replication during lytic reactivation. We also show that RTA regulates ORF59 promoter through interaction with RBP-Jκ as well as a cis-acting RTA responsive element within the promoter. In the context of KSHV infected cells, the upregulation of ORF59 is a direct response to RTA expression. Taken together, our findings provide new evidence to explain the mechanism by which RTA can regulate its downstream gene ORF59, further increasing our understanding of the biology of KSHV lytic replication.
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