Herpes simplex ICP27 mutant viruses exhibit reduced expression of specific DNA replication genes
Herpes simplex ICP27 mutant viruses exhibit reduced expression of specific DNA replication genes
复制标题
DOI：
10.1128/jvi.70.3.1969-1980.1996
复制
发表时间：
1996-03
影响因子：
5.4
通讯作者：
S. Uprichard;D. Knipe
中科院分区：
文献类型：
--
作者：
S. Uprichard;D. Knipe
具有特定ICP27基因损伤的单纯疱疹病毒1型突变体显示病毒DNA合成减少5至10倍。为了确定ICP27如何促进病毒DNA扩增，我们在整个ICP27突变病毒感染过程中检测了必要的病毒复制蛋白的合成、积累和稳定性，以及复制基因转录物的稳态水平。这些研究表明，在缺乏ICP27的情况下，UL5、UL8、UL52、UL9、UL42和UL30基因的表达在mRNA积累水平上显著降低。与这些β基因相反，在突变病毒感染的细胞中，ICP8的表达没有改变，这表明ICP27只选择性地刺激了单纯疱疹病毒β基因的一个子集。对多个ICP27突变病毒的分析表明，这些突变体复制病毒DNA的能力与每个突变体产生的复制蛋白水平之间存在定量相关性。因此，我们得出结论，在感染ICP27突变体的细胞中，导致病毒DNA合成受限的主要缺陷是大多数必需复制基因的表达不足。更令人感兴趣的是，该分析还提供了有关UL52基因转录本结构的新信息。
Herpes simplex virus type 1 mutants with certain lesions in the ICP27 gene show a 5- to 10-fold reduction in viral DNA synthesis. To determine how ICP27 promotes amplification of viral DNA, we examined the synthesis, accumulation, and stability of the essential viral replication proteins and steady-state levels of the replication gene transcripts throughout the course of ICP27 mutant virus infections. These studies reveal that in the absence of ICP27, expression of the UL5, UL8, UL52, UL9, UL42, and UL30 genes is significantly reduced at the level of mRNA accumulation. In contrast to that of these beta genes, ICP8 expression is unaltered in mutant virus-infected cells, indicating that ICP27 selectively stimulates only a subset of herpes simplex virus beta genes. Analysis of multiple ICP27 mutant viruses indicates a quantitative correlation between the ability of these mutants to replicate viral DNA and the level of replication proteins produced by each mutant. Therefore, we conclude that the primary defect responsible for restricted viral DNA synthesis in cells infected with ICP27 mutants is insufficient expression of most of the essential replication genes. Of further interest, this analysis also provides new information about the structure of the UL52 gene transcripts.