The neuronal host cell factor-binding protein Zhangfei inhibits herpes simplex virus replication
The neuronal host cell factor-binding protein Zhangfei inhibits herpes simplex virus replication
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DOI：
10.1128/jvi.79.23.14708-14718.2005
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发表时间：
2005-12-01
影响因子：
5.4
通讯作者：
Misra, V
中科院分区：
文献类型：
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作者：
Akhova, O;Bainbridge, M;Misra, V
在上皮细胞中的裂解性感染期间，I型单纯疱疹病毒（HSV-1）立即早期（IE）基因的表达由包含病毒体相关蛋白VP 16和两种细胞蛋白（宿主细胞因子（HCF）和Oct-1）的多蛋白复合物启动。Oct-1直接识别IE基因启动子中的TAATGARAT元件。HCF的作用尚不明确。HSV-1还感染支配生产性感染部位的感觉神经元，并在这些细胞中建立潜伏感染。很可能一些VP 16在其到达神经元核时被HSV-1核衣壳保留。因此，为了成功建立病毒潜伏期，必须抑制其活性。最近，我们发现了一种名为Zhangfei的HCF结合细胞蛋白。章飞对另一种细胞内的HCF结合转录因子Luman/LZIP/CREB 3具有HCF依赖性抑制作用。在这里，我们表明Zhangfei在人类神经元中选择性表达。当将VP 16递送到通常不表达蛋白质的培养细胞中时，Zhangfei抑制了VP 16激活HSV-1 IE表达的能力。抑制是特异性的HCF依赖性转录激活的VP 16，因为Gal 4-VP 16嵌合蛋白被抑制，只有在TAATGARAT-含有启动子，而不是在Gal 4-含有启动子。张飞与VP 16结合，抑制了VP 16-HCF-Oct-1复合物在TAATGARAT基序上的形成。Zhangfei还抑制了HSV-1诱导的几种细胞基因的表达，包括拓扑异构酶Hot，这表明除了抑制IE表达外，Zhangfei还可能对HSV-1 DNA复制和晚期基因表达具有抑制作用。
During lytic infection in epithelial cells the expression of herpes simplex virus type I (HSV-1) immediate-early (IE) genes is initiated by a multiprotein complex comprising the virion-associated protein VP16 and two cellular proteins, host cellular factor (HCF) and Oct-1. Oct-1 directly recognizes TAATGARAT elements in promoters of IE genes. The role of HCF is not clear. HSV-1 also infects sensory neurons innervating the site of productive infection and establishes a latent infection in these cells. It is likely that some VP16 is retained by the HSV-1 nucleocapsid as it reaches the neuronal nucleus. Its activity must therefore be suppressed for successful establishment of viral latency. Recently, we discovered an HCF-binding cellular protein called Zhangfei. Zhangfei, in an HCF-dependent manner, inhibits Luman/LZIP/CREB3, another cellular HCFbinding transcription factor. Here we show that Zhangfei is selectively expressed in human neurons. When delivered to cultured cells that do not normally express the protein, Zhangfei inhibited the ability of VP16 to activate HSV-1 IE expression. The inhibition was specific for HCF-dependent transcriptional activation by VP16, since a Gal4-VP16 chimeric protein was inhibited only on a TAATGARAT-containing promoter and not a on a Gal4-containing promoter. Zhangfei associated with VP16 and inhibited formation of the VP16-HCF-Oct-1 complex on TAATGARAT motifs. Zhangfei also suppressed HSV-1-induced expression of several cellular genes including topoisomerase Hot, suggesting that in addition to suppressing IE expression Zhangfei may have an inhibitory effect on HSV-1 DNA replication and late gene expression.