Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, PA 15219.
Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, PA 15219
Proc Natl Acad Sci U S A. 2019 Feb 26;116(9):3734-3739. doi: 10.1073/pnas.1818463116. Epub 2019 Feb 11.
In herpes simplex virus type 1 (HSV-1) infection, the coupling of genome replication and transcription regulation has been known for many years; however, the underlying mechanism has not been elucidated. We performed a comprehensive transcriptomic assessment and factor-binding analysis for Pol II, TBP, TAF1, and Sp1 to assess the effect genome replication has on viral transcription initiation and elongation. The onset of genome replication resulted in the binding of TBP, TAF1, and Pol II to previously silent late promoters. The viral transcription factor, ICP4, was continuously needed in addition to DNA replication for activation of late gene transcription initiation. Furthermore, late promoters contain a motif that closely matches the consensus initiator element (Inr), which robustly bound TAF1 postreplication. Continued DNA replication resulted in reduced binding of Sp1, TBP, and Pol II to early promoters. Therefore, the initiation of early gene transcription is attenuated following DNA replication. Herein, we propose a model for how viral DNA replication results in the differential utilization of cellular factors that function in transcription initiation, leading to the delineation of kinetic class in HSV-productive infection.
在单纯疱疹病毒 1 型（HSV-1）感染中，基因组复制和转录调控的偶联已经为人所知多年；然而，其潜在的机制尚未阐明。我们进行了全面的转录组评估和 Pol II、TBP、TAF1 和 Sp1 的因子结合分析，以评估基因组复制对病毒转录起始和延伸的影响。基因组复制的开始导致 TBP、TAF1 和 Pol II 结合到先前沉默的晚期启动子上。除了 DNA 复制之外，病毒转录因子 ICP4 也持续需要激活晚期基因转录起始。此外，晚期启动子包含一个与共识起始元件 (Inr) 非常匹配的模体，该模体在复制后能强烈结合 TAF1。持续的 DNA 复制导致 Sp1、TBP 和 Pol II 与早期启动子的结合减少。因此，早期基因转录的起始在 DNA 复制后受到抑制。在此，我们提出了一个模型，说明病毒 DNA 复制如何导致细胞因子在转录起始中的差异利用，从而导致 HSV 复制感染中动力学类别的划分。
