Roizman B
Marjorie B. Kovler Viral Oncology Laboratories, University of Chicago, IL 60637, USA.
Acta Virol. 1999 Apr-Jun;43(2-3):75-80.
Herpes simplex virus 1 (HSV-1) encodes at least 84 polypeptides to perform two functions: to enable viral replication and to create the environment in which the entry of the virus into host cells, synthesis of virion components, assembly and egress are optimized. Whereas the former are indispensable for viral replication, the latter, numbering 47, can be deleted without a major effect on viral replication in cells in culture. Of particular interest are gene products whose function is either to modify cellular proteins (set 1) or to block entirely their function (set 2). An example of set 1 is the infected cell protein No. 0 (ICP0), a promiscuous transactivator of genes introduced into cells by infection or transfection. In its nuclear phase this protein binds to cyclin D3, extends its life by many hours, and sequesters it in nuclear structures known as ND10. In its cytoplasmic phase, ICP0 binds the translation elongation factor EF-1 delta. Another viral protein, the UL13 protein kinase, hyper-phosphorylates EF-1 delta. ICP0 and the protein kinase stimulate protein synthesis and cause the cell to induce the synthesis of pre-S phase cellular proteins the virus needs for its replication. The gamma 134.5 protein, a prototype of set 2, also has multiple functions. One, mapped at its carboxyl terminus, blocks the effects of double-stranded RNA-dependent protein kinase R (PKR) that is activated by all wild-type and mutant viruses examined to date. PKR phosphorylates eIF-2 alpha and shuts off protein synthesis. gamma 134.5 protein binds protein phosphatase 1 and redirects it to dephosphorylate eIF-2 alpha. Although PKR is activated in wild-type-infected cells, protein synthesis is unaffected. HSV-1 encodes in addition at least two proteins, ORF O and ORF P that are repressed during productive infection. The ORF P protein localizes in spliceosomes and blocks the synthesis of viral proteins derived from spliced mRNA. The ORF O protein binds ICP4, the major regulatory protein, and prevents it from binding to DNA. The role of ORF O and ORF P proteins in the establishment of latency is uncertain. A significant discovery that has emerged from these studies is that viral proteins can perform several functions that may be totally unrelated.
单纯疱疹病毒1型（HSV - 1）编码至少84种多肽以执行两种功能：实现病毒复制以及创造有利于病毒进入宿主细胞、病毒体成分合成、组装和释放的环境并使其最优化。前者对病毒复制不可或缺，而后者（共47种）即使被删除，对培养细胞中的病毒复制也没有重大影响。特别令人感兴趣的是那些功能为修饰细胞蛋白（第1组）或完全阻断其功能（第2组）的基因产物。第1组的一个例子是感染细胞蛋白0（ICP0），它是一种通过感染或转染导入细胞的基因的混杂反式激活因子。在其核阶段，这种蛋白与细胞周期蛋白D3结合，将其寿命延长数小时，并将其隔离在称为ND10的核结构中。在其胞质阶段，ICP0与翻译延伸因子EF - 1δ结合。另一种病毒蛋白，UL13蛋白激酶，使EF - 1δ发生过度磷酸化。ICP0和蛋白激酶刺激蛋白质合成，并使细胞诱导合成病毒复制所需的S期前细胞蛋白。γ134.5蛋白是第2组的一个原型，也具有多种功能。一种功能定位于其羧基末端，可阻断双链RNA依赖性蛋白激酶R（PKR）的作用，PKR可被迄今为止检测的所有野生型和突变型病毒激活。PKR使真核起始因子2α（eIF - 2α）磷酸化并关闭蛋白质合成。γ134.5蛋白结合蛋白磷酸酶1并使其重新定向去磷酸化eIF - 2α。尽管在野生型感染的细胞中PKR被激活，但蛋白质合成不受影响。HSV - 1还编码至少另外两种蛋白，即开放阅读框O（ORF O）和开放阅读框P（ORF P），它们在增殖性感染期间受到抑制。ORF P蛋白定位于剪接体中，并阻断源自剪接mRNA的病毒蛋白的合成。ORF O蛋白与主要调节蛋白ICP4结合，并阻止其与DNA结合。ORF O和ORF P蛋白在潜伏建立中的作用尚不确定。这些研究中出现的一个重要发现是，病毒蛋白可以执行几种可能完全不相关的功能。
