Narayanan Aarthi, Nogueira Mauricio L, Ruyechan William T, Kristie Thomas M
Laboratory of Viral Diseases, NIAID, National Institutes of Health, Bethesda, Maryland 20892, USA.
J Biol Chem. 2005 Jan 14;280(2):1369-75. doi: 10.1074/jbc.M410178200. Epub 2004 Nov 1.
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.
哺乳动物转录共激活因子宿主细胞因子-1（HCF-1）与Oct-1和VP16协同作用，组装单纯疱疹病毒（HSV）立即早期（IE）转录增强子核心复合物，该复合物在感染后介导这些基因的高水平转录。尽管这种转录模型在体外已得到充分表征，但尚未探讨其组成成分的需求和意义。此前已确定Oct-1对HSV IE基因表达至关重要但并非必不可少。相比之下，RNA干扰介导的HCF-1缺失导致HSV IE基因表达被消除。HSV IE基因增强子结构域是一个组合转录模型，由核心增强子以及Sp1和GA结合蛋白等因子的多个结合位点组成。引人注目的是，HCF-1对于通过核心增强子的VP16介导的转录诱导以及由GA结合蛋白和Sp1介导的基础水平转录都是严格必需的。还发现HCF-1对于由ORF10（HSV IE反式激活因子VP16的水痘带状疱疹病毒直系同源物）和自刺激IE62蛋白诱导水痘带状疱疹病毒IE基因表达也是必不可少的。对HCF-1的关键依赖性表明，这种细胞成分是通过作为在IE基因增强子处协同作用的不同因子的共同元件来控制HSV和VZV IE基因表达的关键因素。对这种蛋白质的需求支持了这样一种模型，即感觉神经元中HCF-1从细胞质到细胞核的调节转运可能控制IE基因表达以及这些病毒从潜伏状态的重新激活。
