McArdle Laboratory for Cancer Research, University of Wisconsin-Madison, Madison, Wisconsin, USA.
Department of Medicine, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, Wisconsin, USA.
J Virol. 2019 Apr 3;93(8). doi: 10.1128/JVI.02247-18. Print 2019 Apr 15.
The Epstein-Barr virus (EBV) lytic phase, like those of all herpesviruses, proceeds via an orderly cascade that integrates DNA replication and gene expression. EBV early genes are expressed independently of viral DNA amplification, and several early gene products facilitate DNA amplification. On the other hand, EBV late genes are defined by their dependence on viral DNA replication for expression. Recently, a set of orthologous genes found in beta- and gammaherpesviruses have been determined to encode a viral preinitiation complex (vPIC) that mediates late gene expression. The EBV vPIC requires an origin of lytic replication in , implying that the vPIC mediates transcription from newly replicated DNA. In agreement with this implication, EBV late gene mRNAs localize to replication factories. Notably, these factories exclude canonical histones. In this review, we compare and contrast the mechanisms and epigenetics of EBV early and late gene expression. We summarize recent findings, propose a model explaining the dependence of EBV late gene expression on lytic DNA amplification, and suggest some directions for future study.
EBV 病毒（EBV）裂解期，与所有疱疹病毒一样，通过一个有序的级联进行，整合 DNA 复制和基因表达。EBV 早期基因的表达独立于病毒 DNA 扩增，并且几个早期基因产物促进 DNA 扩增。另一方面，EBV 晚期基因的定义是它们依赖于病毒 DNA 复制进行表达。最近，已经确定在β和γ疱疹病毒中发现的一组同源基因编码一种病毒起始复合物（vPIC），该复合物介导晚期基因表达。EBV vPIC 需要在 中裂解复制的起点，这意味着 vPIC 介导从新复制的 DNA 转录。这一含义与 EBV 晚期基因 mRNAs 定位于复制工厂的事实一致。值得注意的是，这些工厂排除了典型的组蛋白。在这篇综述中，我们比较和对比了 EBV 早期和晚期基因表达的机制和表观遗传学。我们总结了最近的发现，提出了一个解释 EBV 晚期基因表达依赖于裂解 DNA 扩增的模型，并提出了一些未来研究的方向。
