Spencer C A, Dahmus M E, Rice S A
Department of Biochemistry, University of Alberta, Edmonton, Canada.
J Virol. 1997 Mar;71(3):2031-40. doi: 10.1128/JVI.71.3.2031-2040.1997.
Lytic infection of mammalian cells with herpes simplex virus type 1 (HSV-1) results in rapid repression of host gene expression and selective activation of the viral genome. This transformation in gene expression is thought to involve repression of host transcription and diversion of the host RNA polymerase (RNAP II) transcription machinery to the viral genome. However, the extent of virus-induced host transcription repression and the mechanisms responsible for these major shifts in transcription specificities have not been examined. To determine how HSV-1 accomplishes repression of host RNAP II transcription, we assayed transcription patterns on several cellular genes in cells infected with mutant and wild-type HSV-1. Our results suggest that HSV-1 represses RNAP II transcription on most cellular genes. However, each cellular gene we examined responds differently to the transcription repressive effects of virus infection, both quantitatively and with respect to the involvement of viral gene products. Virus-induced shutoff of host RNAP II transcription requires expression of multiple immediate-early genes. In contrast, expression of delayed-early and late genes and viral DNA replication appear to contribute little to repression of host cell RNAP II transcription. Modification of RNAP II to the intermediately phosphorylated (II(I)) form appears unlinked to virus-induced repression of host cell transcription. However, full repression of host transcription is correlated with depletion of the hyperphosphorylated (IIO) form of RNAP II.
1型单纯疱疹病毒（HSV-1）对哺乳动物细胞的裂解性感染导致宿主基因表达迅速受到抑制，同时病毒基因组被选择性激活。这种基因表达的转变被认为涉及宿主转录的抑制以及宿主RNA聚合酶（RNAP II）转录机制向病毒基因组的转移。然而，病毒诱导的宿主转录抑制程度以及导致转录特异性发生这些重大转变的机制尚未得到研究。为了确定HSV-1如何实现对宿主RNAP II转录的抑制，我们检测了感染突变型和野生型HSV-1的细胞中几个细胞基因的转录模式。我们的结果表明，HSV-1抑制了大多数细胞基因上的RNAP II转录。然而，我们检测的每个细胞基因对病毒感染的转录抑制作用的反应在数量上以及在病毒基因产物的参与方面都有所不同。病毒诱导的宿主RNAP II转录关闭需要多个立即早期基因的表达。相比之下，延迟早期和晚期基因的表达以及病毒DNA复制似乎对宿主细胞RNAP II转录的抑制作用很小。RNAP II向中间磷酸化（II(I)）形式的修饰似乎与病毒诱导的宿主细胞转录抑制无关。然而，宿主转录的完全抑制与RNAP II的超磷酸化（IIO）形式的消耗相关。
