Combinatorial transcription of herpes simplex virus and varicella zoster virus immediate early genes is strictly determined by the cellular coactivator HCF-1
Combinatorial transcription of herpes simplex virus and varicella zoster virus immediate early genes is strictly determined by the cellular coactivator HCF-1
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DOI：
10.1074/jbc.m410178200
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发表时间：
2005-01-14
影响因子：
4.8
通讯作者：
Kristie, TM
中科院分区：
文献类型：
--
作者：
Narayanan, A;Nogueira, ML;Kristie, TM
哺乳动物转录辅激活因子宿主细胞因子 1 (HCF-1) 与 Oct-1 和 VP16 协同发挥作用，组装单纯疱疹病毒 (HSV) 立即早期 (IE) 转录增强子核心复合物，在感染时介导这些基因的高水平转录。尽管这种转录模型已在体外得到了很好的表征，但其组成部分的要求和意义尚未得到解决。 Oct-1 先前被确定对于 HSV IE 基因表达至关重要但不是必需的。相反，RNA干扰介导的HCF-1耗竭导致HSV IE基因表达消失。 HSV IE基因增强子结构域是组合转录的模型，由核心增强子和Sp1和GA结合蛋白等因子的多个结合位点组成。令人惊讶的是，HCF-1 是 VP16 通过核心增强子介导的转录诱导以及 GA 结合蛋白和 Sp1 介导的基础水平转录严格必需的。还发现 HCF-1 对于 ORF10（HSV IE 反式激活子 VP16 的 VZV 直向同源物）和自刺激 IE62 蛋白诱导水痘带状疱疹病毒 IE 基因表达至关重要。对 HCF-1 的关键依赖性表明，该细胞成分是控制 HSV 和 VZV IE 基因表达的关键因素，通过充当与 IE 基因增强子合作的不同因子的共同元件。对这种蛋白质的需求支持了这样的模型：HCF-1在感觉神经元中从细胞质到细胞核的受调节运输可以控制IE基因表达和这些病毒从潜伏状态的重新激活。
The mammalian transcriptional coactivator host cell factor-1 (HCF-1) functions in concert with Oct-1 and VP16 to assemble the herpes simplex virus (HSV) immediate early (IE) transcription enhancer core complexes that mediate the high level transcription of these genes upon infection. Although this transcriptional model has been well characterized in vitro, the requirements and significance of the components have not been addressed. Oct-1 was previously determined to be critical but not essential for HSV IE gene expression. In contrast, RNA interference-mediated depletion of HCF-1 resulted in abrogation of HSV IE gene expression. The HSV IE gene enhancer domain is a model of combinatorial transcription and consists of the core enhancer and multiple binding sites for factors such as Sp1 and GA-binding protein. It was striking that HCF-1 was strictly required for VP16-mediated transcriptional induction via the core enhancer as well as for basal level transcription mediated by GA-binding protein and Sp1. HCF-1 was also found to be essential for the induction of varicella zoster virus IE gene expression by ORF10, the VZV ortholog of the HSV IE transactivator VP16, and the autostimulatory IE62 protein. The critical dependence upon HCF-1 demonstrates that this cellular component is a key factor for control of HSV and VZV IE gene expression by functioning as the common element for distinct factors cooperating at the IE gene enhancers. The requirements for this protein supports the model whereby the regulated transport of HCF-1 from the cytoplasm to the nucleus in sensory neurons may control IE gene expression and reactivation of these viruses from the latent state.