SARS-CoV-2 通过组蛋白模仿破坏宿主表观遗传调控。由ORF8编码的新冠病毒蛋白，可作为组蛋白 H3 中 ARKS 基序模拟物来破坏宿主细胞的表观遗传调控，抑制抗病毒反应。本文是新冠病毒感染，表观遗传学关联发病机理的基础医学研究论文。
(Baidu Translation: )
Nature: COVID-19 destroys host epigenetic regulation by mimicking histones
SARS CoV-2 destroys host epigenetic regulation through histone mimicry. The COVID-19 protein encoded by ORF8 can be used as a mimic of the ARKS motif in histone H3 to destroy the epigenetic regulation of host cells and inhibit the antiviral response. This is a basic medical research paper on the pathogenesis of COVID-19 infection associated with epigenetics.
（百度翻訳：）
Nature：新型コロナウイルスはアナログ組タンパク質による宿主の見かけ上の遺伝的制御を破壊する
SARS−CoV−2は、ヒストン模倣により宿主の見かけ上の遺伝的制御を破壊する。ORF 8によって符号化された新規コロナウイルスタンパク質は、グループタンパク質H 3中のARKS基序シミュレーション物として宿主細胞の見かけ上の遺伝制御を破壊し、抗ウイルス反応を抑制することができる。本文は新型コロナウイルス感染、遺伝学関連発病機序を概観する基礎医学研究論文である。
领研网
2022/10/24
论文
论文标题：SARS-CoV-2 disrupts host epigenetic regulation via histone mimicry
作者：John Kee, Samuel Thudium, David M. Renner, Karl Glastad, Katherine Palozola, Zhen Zhang, Yize Li, Yemin Lan, Joseph Cesare, Andrey Poleshko, Anna A. Kiseleva, et al.
期刊：Nature
发表时间：2022/10/05
数字识别码：10.1038/s41586-022-05282-z
摘要：Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged at the end of 2019 and caused the devastating global pandemic of coronavirus disease 2019 (COVID-19), in part because of its ability to effectively suppress host cell responses1,2,3. In rare cases, viral proteins dampen antiviral responses by mimicking critical regions of human histone proteins4,5,6,7,8, particularly those containing post-translational modifications required for transcriptional regulation9,10,11. Recent work has demonstrated that SARS-CoV-2 markedly disrupts host cell epigenetic regulation12,13,14. However, how SARS-CoV-2 controls the host cell epigenome and whether it uses histone mimicry to do so remain unclear. Here we show that the SARS-CoV-2 protein encoded by ORF8 (ORF8) functions as a histone mimic of the ARKS motifs in histone H3 to disrupt host cell epigenetic regulation. ORF8 is associated with chromatin, disrupts regulation of critical histone post-translational modifications and promotes chromatin compaction. Deletion of either the ORF8 gene or the histone mimic site attenuates the ability of SARS-CoV-2 to disrupt host cell chromatin, affects the transcriptional response to infection and attenuates viral genome copy number. These findings demonstrate a new function of ORF8 and a mechanism through which SARS-CoV-2 disrupts host cell epigenetic regulation. Further, this work provides a molecular basis for the finding that SARS-CoV-2 lacking ORF8 is associated with decreased severity of COVID-19.
