Samaniego L A, Webb A L, DeLuca N A
Department of Molecular Genetics and Biochemistry, University of Pittsburgh School of Medicine, Pennsylvania 15261, USA.
J Virol. 1995 Sep;69(9):5705-15. doi: 10.1128/JVI.69.9.5705-5715.1995.
Two of the five immediate-early gene products, ICP4 and ICP27, expressed by herpes simplex virus type 1 have profound effects on viral gene expression and are absolutely essential for virus replication. Functional interactions between ICP4 and ICP27 may contribute to establishing the program of viral gene expression that ensues during lytic infection. To evaluate this possibility, viral mutants simultaneously deleted for ICP27 and defined functional domains of ICP4 were constructed. These mutant viruses allowed a comparison of gene expression as a function of different domains of ICP4 in the presence and absence of ICP27. Gene expression in the absence of both ICP4 and ICP27 was also examined. The results of this study demonstrate a clear involvement for ICP27 in the induction of early genes, in addition to its known role in enhancing late gene expression during viral infection. In the absence of both ICP4 and ICP27, viral early gene expression, as measured by the accumulation of thymidine kinase and ICP6 messages was dramatically reduced relative to the amounts of these messages seen in the absence of only ICP4. Therefore, elevated levels of early gene expression as a consequence of ICP27 occurred in the absence of any ICP4 activity. Evidence is also presented regarding the modulation of the ICP4 repression function by ICP27. When synthesized in the absence of ICP27, a mutant ICP4 protein was impaired in its ability to repress transcription from the L/ST promoter in the context of viral infection and in vitro. This defect correlated with the loss of the ability of this mutant protein to bind to its recognition sequence when produced in infected cells in the absence of ICP27. These observations indicate that ICP27 can regulate the activity of at least one domain of the ICP4 protein as well as contribute to elevated early gene expression independently of ICP4.
1型单纯疱疹病毒表达的5种立即早期基因产物中的两种，即ICP4和ICP27，对病毒基因表达有深远影响，并且对病毒复制绝对必要。ICP4和ICP27之间的功能相互作用可能有助于建立在裂解感染期间随之而来的病毒基因表达程序。为了评估这种可能性，构建了同时缺失ICP27和ICP4特定功能域的病毒突变体。这些突变病毒允许比较在有和没有ICP27的情况下，作为ICP4不同结构域功能的基因表达。还研究了在没有ICP4和ICP27两者的情况下的基因表达。这项研究的结果表明，除了其在病毒感染期间增强晚期基因表达的已知作用外，ICP27还明显参与早期基因的诱导。在没有ICP4和ICP27两者的情况下，相对于仅没有ICP4时所见的这些信息的量，通过胸苷激酶和ICP6信息的积累测量的病毒早期基因表达显著降低。因此，在没有任何ICP4活性的情况下，由于ICP27导致早期基因表达水平升高。还提供了关于ICP27对ICP4抑制功能调节的证据。当在没有ICP27的情况下合成时，一种突变的ICP4蛋白在病毒感染和体外的情况下抑制L/ST启动子转录的能力受损。当在没有ICP27的感染细胞中产生时，这种缺陷与该突变蛋白结合其识别序列的能力丧失相关。这些观察结果表明，ICP27可以调节ICP4蛋白至少一个结构域的活性，并且还可以独立于ICP4促进早期基因表达的升高。
