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Epigenetic and epitranscriptomic regulation of viral replication.
Nature Reviews Microbiology ( IF 88.1 ) Pub Date : 2020-06-12 , DOI: 10.1038/s41579-020-0382-3
Kevin Tsai 1 , Bryan R Cullen 1
Affiliation  

Eukaryotic gene expression is regulated not only by genomic enhancers and promoters, but also by covalent modifications added to both chromatin and RNAs. Whereas cellular gene expression may be either enhanced or inhibited by specific epigenetic modifications deposited on histones (in particular, histone H3), these epigenetic modifications can also repress viral gene expression, potentially functioning as a potent antiviral innate immune response in DNA virus-infected cells. However, viruses have evolved countermeasures that prevent the epigenetic silencing of their genes during lytic replication, and they can also take advantage of epigenetic silencing to establish latent infections. By contrast, the various covalent modifications added to RNAs, termed epitranscriptomic modifications, can positively regulate mRNA translation and/or stability, and both DNA and RNA viruses have evolved to utilize epitranscriptomic modifications as a means to maximize viral gene expression. As a consequence, both chromatin and RNA modifications could serve as novel targets for the development of antivirals. In this Review, we discuss how host epigenetic and epitranscriptomic processes regulate viral gene expression at the levels of chromatin and RNA function, respectively, and explore how viruses modify, avoid or utilize these processes in order to regulate viral gene expression.



中文翻译:

病毒复制的表观遗传和表观转录组调控。

真核基因表达不仅受基因组增强子和启动子的调节,还受到染色质和 RNA 中添加的共价修饰的调节。尽管细胞基因表达可能通过沉积在组蛋白(特别是组蛋白 H3)上的特定表观遗传修饰而增强或抑制,但这些表观遗传修饰也可以抑制病毒基因表达,可能在 DNA 病毒感染的细胞中发挥有效的抗病毒先天免疫反应的作用. 然而,病毒已经进化出防止其基因在裂解复制过程中的表观遗传沉默的对策,并且它们还可以利用表观遗传沉默来建立潜伏感染。相比之下,添加到 RNA 中的各种共价修饰,称为表观转录组修饰,可以正向调节 mRNA 翻译和/或稳定性,DNA 和 RNA 病毒都已经进化到利用表观转录组修饰作为最大化病毒基因表达的手段。因此,染色质和 RNA 修饰都可以作为开发抗病毒药物的新靶点。在这篇综述中,我们讨论了宿主表观遗传和表观转录组过程如何分别在染色质和 RNA 功能水平调节病毒基因表达,并探讨病毒如何修改、避免或利用这些过程来调节病毒基因表达。

更新日期:2020-06-12
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