Knipe D M
Department of Microbiology and Molecular Genetics, Harvard Medical School, Boston, Massachusetts 02115.
Adv Virus Res. 1989;37:85-123. doi: 10.1016/s0065-3527(08)60833-7.
Following infection of cells by herpes simplex virus, the cell nucleus is subverted for transcription and replication of the viral genome and assembly of progeny nucleocapsids. The transition from host to viral transcription involves viral proteins that influence the ability of the cellular RNA polymerase II to transcribe a series of viral genes. The regulation of RNA polymerase II activity by viral gene products seems to occur by several different mechanisms: (1) viral proteins complex with cellular proteins and alter their transcription-promoting activity (e.g., alpha TIF), (2) viral proteins bind to specific DNA sequences and alter transcription (e.g., ICP4), and (3) viral proteins affect the posttranslational modification of viral or cellular transcriptional regulatory proteins (e.g., possibly ICP27). Thus, HSV may utilize several different approaches to influence the ability of host-cell RNA polymerase II to transcribe viral genes. Although it is known that viral transcription uses the host-cell polymerase II, it is not known whether viral infection causes a change in the structural elements of the nucleus that promote transcription. In contrast, HSV encodes a new DNA polymerase and accessory proteins that complex with and reorganize cellular proteins to form new structures where viral DNA replication takes place. HSV may encode a large number of DNA replication proteins, including a new polymerase, because it replicates in resting cells where these cellular gene products would never be expressed. However, it imitates the host cell in that it localizes viral DNA replication proteins to discrete compartments of the nucleus where viral DNA synthesis takes place. Furthermore, there is evidence that at least one specific viral gene protein can play a role in organizing the assembly of the DNA replication structures. Further work in this system may determine whether assembly of these structures is essential for efficient viral DNA replication and if so, why assembly of these structures is necessary. Thus, the study of the localization and assembly of HSV DNA replication proteins provides a system to examine the mechanisms involved in morphogenesis of the cell nucleus. Therefore, several critical principles are apparent from these discussions of the metabolism of HSV transcription and DNA replication. First, there are many ways in which the activity of RNA polymerase II can be regulated, and HSV proteins exploit several of these in controlling the transcription of a single DNA molecule. Second, the interplay of these multiple regulatory pathways is likely to control the progress of the lytic cycle and may play a role in determining the lytic versus latent infection decision.(ABSTRACT TRUNCATED AT 400 WORDS)
单纯疱疹病毒感染细胞后，细胞核被用于病毒基因组的转录、复制以及子代核衣壳的组装。从宿主转录向病毒转录的转变涉及一些病毒蛋白，这些蛋白会影响细胞RNA聚合酶II转录一系列病毒基因的能力。病毒基因产物对RNA聚合酶II活性的调控似乎通过几种不同机制发生：（1）病毒蛋白与细胞蛋白形成复合物并改变其转录促进活性（例如αTIF），（2）病毒蛋白结合特定DNA序列并改变转录（例如ICP4），以及（3）病毒蛋白影响病毒或细胞转录调节蛋白的翻译后修饰（例如可能是ICP27）。因此，单纯疱疹病毒可能利用几种不同方法来影响宿主细胞RNA聚合酶II转录病毒基因的能力。虽然已知病毒转录使用宿主细胞的聚合酶II，但尚不清楚病毒感染是否会导致促进转录的细胞核结构元件发生变化。相比之下，单纯疱疹病毒编码一种新的DNA聚合酶和辅助蛋白，这些蛋白与细胞蛋白形成复合物并使其重新组织，以形成进行病毒DNA复制的新结构。单纯疱疹病毒可能编码大量DNA复制蛋白，包括一种新的聚合酶，因为它在静止细胞中复制，而这些细胞基因产物在静止细胞中永远不会表达。然而，它在将病毒DNA复制蛋白定位到细胞核中发生病毒DNA合成的离散区室方面模仿宿主细胞。此外，有证据表明至少一种特定的病毒基因蛋白可以在组织DNA复制结构的组装中发挥作用。在这个系统中进一步的研究可能会确定这些结构的组装对于有效的病毒DNA复制是否必不可少，如果是，那么为什么这些结构的组装是必要的。因此，对单纯疱疹病毒DNA复制蛋白的定位和组装的研究提供了一个系统来研究参与细胞核形态发生的机制。因此，从这些关于单纯疱疹病毒转录和DNA复制代谢的讨论中可以明显看出几个关键原则。首先，RNA聚合酶II的活性有多种调节方式，单纯疱疹病毒蛋白在控制单个DNA分子的转录过程中利用了其中几种方式。其次，这些多种调节途径的相互作用可能控制裂解周期的进程，并可能在决定裂解性感染与潜伏性感染的决策中发挥作用。（摘要截断于400字）
