Human Biology Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA, USA.
FEBS Lett. 2019 Dec;593(24):3551-3570. doi: 10.1002/1873-3468.13697. Epub 2019 Dec 15.
The DNA genome of eukaryotic cells is compacted by histone proteins within the nucleus to form chromatin. Nuclear-replicating viruses such as adenovirus have evolved mechanisms of chromatin manipulation to promote infection and subvert host defenses. Epigenetic factors may also regulate persistent adenovirus infection and reactivation in lymphoid tissues. In this review, we discuss the viral proteins E1A and protein VII that interact with and alter host chromatin, as well as E4orf3, which separates host chromatin from sites of viral replication. We also highlight recent advances in chromatin technologies that offer new insights into virus-directed chromatin manipulation. Beyond the role of chromatin in the viral replication cycle, we discuss the nature of persistent viral genomes in lymphoid tissue and cell lines, and the potential contribution of epigenetic signals in maintaining adenovirus in a quiescent state. By understanding the mechanisms through which adenovirus manipulates host chromatin, we will understand new aspects of this ubiquitous virus and shed light on previously unknown aspects of chromatin biology.
真核细胞的 DNA 基因组在细胞核内被组蛋白压缩形成染色质。核复制病毒,如腺病毒,已经进化出染色质操作的机制,以促进感染并颠覆宿主防御。表观遗传因素也可能调节淋巴组织中持续性腺病毒感染和再激活。在这篇综述中,我们讨论了与宿主染色质相互作用并改变宿主染色质的病毒蛋白 E1A 和蛋白 VII,以及将宿主染色质与病毒复制位点分离的 E4orf3。我们还强调了染色质技术的最新进展,这些进展为病毒指导的染色质操作提供了新的见解。除了染色质在病毒复制周期中的作用外,我们还讨论了淋巴组织和细胞系中持续性病毒基因组的性质,以及表观遗传信号在维持腺病毒静止状态中的潜在作用。通过了解腺病毒如何操纵宿主染色质的机制,我们将了解这种普遍存在的病毒的新方面,并揭示染色质生物学的未知方面。