Guangzhou National Laboratory, Guangzhou, 510320, China.
Department of Microbiology, University of Helsinki, Helsinki, 00014, Finland.
FEMS Microbiol Rev. 2024 Sep 18;48(5). doi: 10.1093/femsre/fuae023.
Infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes widespread changes in epigenetic modifications and chromatin architecture in the host cell. Recent evidence suggests that SARS-CoV-2 nonstructural protein 1 (nsp1) plays an important role in driving these changes. Previously thought to be primarily involved in host translation shutoff and cellular mRNA degradation, nsp1 has now been shown to be a truly multifunctional protein that affects host gene expression at multiple levels. The functions of nsp1 are surprisingly diverse and include not only the downregulation of cellular mRNA translation and stability, but also the inhibition of mRNA export from the nucleus, the suppression of host immune signaling, and, most recently, the epigenetic regulation of host gene expression. In this review, we first summarize the current knowledge on SARS-CoV-2-induced changes in epigenetic modifications and chromatin structure. We then focus on the role of nsp1 in epigenetic reprogramming, with a particular emphasis on the silencing of immune-related genes. Finally, we discuss potential molecular mechanisms underlying the epigenetic functions of nsp1 based on evidence from SARS-CoV-2 interactome studies.
严重急性呼吸综合征冠状病毒 2（SARS-CoV-2）感染会导致宿主细胞中的表观遗传修饰和染色质结构发生广泛变化。最近的证据表明，SARS-CoV-2 的非结构蛋白 1（nsp1）在驱动这些变化方面起着重要作用。nsp1 以前被认为主要参与宿主翻译关闭和细胞 mRNA 降解，但现在已被证明是一种真正多功能的蛋白质，可在多个层面上影响宿主基因表达。nsp1 的功能令人惊讶地多样化，不仅包括下调细胞 mRNA 翻译和稳定性，还包括抑制 mRNA 从细胞核输出、抑制宿主免疫信号，以及最近对宿主基因表达的表观遗传调控。在这篇综述中，我们首先总结了 SARS-CoV-2 诱导的表观遗传修饰和染色质结构变化的最新知识。然后，我们重点关注 nsp1 在表观遗传重编程中的作用，特别强调对免疫相关基因的沉默。最后，我们根据 SARS-CoV-2 相互作用组研究的证据，讨论了 nsp1 表观遗传功能的潜在分子机制。
