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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Human cytomegalovirus immediate-early 1 protein facilitates viral replication by antagonizing histone deacetylation.
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Human cytomegalovirus immediate-early 1 protein facilitates viral replication by antagonizing histone deacetylation.

机译：人类巨细胞病毒即早1蛋白通过拮抗组蛋白去乙酰化促进病毒复制。

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摘要

The human cytomegalovirus 72-kDa immediate-early (IE)1 and 86-kDa IE2 proteins are expressed at the start of infection, and they are believed to exert much of their function through promiscuous transcriptional activation of viral and cellular gene expression. Here, we show that the impaired growth of an IE1-deficient mutant virus in human fibroblasts is efficiently rescued by histone deacetylase (HDAC) inhibitors of three distinct chemical classes. In the absence of IE1 expression, the viral major IE and UL44 early promoters exhibited decreased de novo acetylation of histone H4 during the early phase of infection, and the hypoacetylation correlated with reduced transcription and accumulation of the respective gene products. Consistent with these findings, IE1 interacts specifically with HDAC3 within infected cells. We also demonstrate an interaction between IE2 and HDAC3. We propose that the ability to modify chromatin is fundamental to transcriptional activation by IE1 and, likely, IE2 as well.
机译：人类巨细胞病毒72 kDa立即（IE）1和86 kDa IE2蛋白在感染开始时就表达了，据信它们通过病毒和细胞基因表达的混杂转录激活发挥其大部分功能。在这里，我们显示人类成纤维细胞中IE1缺陷型突变病毒的受损生长可以通过三种不同化学类别的组蛋白脱乙酰基酶（HDAC）抑制剂有效地挽救。在没有IE1表达的情况下，病毒的主要IE和UL44早期启动子在感染的早期阶段表现出组蛋白H4的从头乙酰化降低，而乙酰化过低与相应基因产物的转录和积累减少相关。与这些发现一致，IE1在感染的细胞内与HDAC3特异性相互作用。我们还演示了IE2和HDAC3之间的交互。我们提出，修饰染色质的能力是IE1以及（也可能是IE2）转录激活的基础。

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