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病毒诱导的 FoxO 因子促进人巨细胞病毒的复制。

Virus-induced FoxO factor facilitates replication of human cytomegalovirus.

机构信息

College of Veterinary Medicine, University of Sulaimani, Sulaymaniyah, Iraq.

Medical Laboratory Science, Komar University of Technology and Sciences, Sulaymaniyah, Iraq.

出版信息

Arch Virol. 2022 Jan;167(1):109-121. doi: 10.1007/s00705-021-05279-5. Epub 2021 Nov 9.

DOI:10.1007/s00705-021-05279-5
PMID:34751815
Abstract

Recently, it was reported that the forkhead box O (FoxO) transcription factor promotes human cytomegalovirus (HCMV) replication via direct binding to the promoters of the major immediate-early (MIE) genes, but how the FoxO factor impacts HCMV replication remains unknown. Here, it is reported that FoxO1 expression is strongly induced by HCMV infection in cells of fibroblast origin. Suppression of the FoxO1 gene by specific RNA interference significantly inhibited HCMV growth and replication, but viral DNA synthesis was not affected considerably. Interestingly, depletion or overexpression of FoxO1 had a significant effect on the expression of viral early/late transcripts. FoxO1 was found to colocalize with the pUL44 protein subunit of viral replication compartments without direct association with DNA. This study highlights how FoxO enhances HCMV gene transcription and viral replication to promote infection.

摘要

最近有报道称,叉头框 O(FoxO)转录因子通过直接结合主要即刻早期(MIE)基因的启动子促进人巨细胞病毒(HCMV)的复制,但 FoxO 因子如何影响 HCMV 的复制尚不清楚。本研究报道 FoxO1 的表达在成纤维细胞来源的细胞中受到 HCMV 感染的强烈诱导。通过特异性 RNA 干扰抑制 FoxO1 基因显著抑制 HCMV 的生长和复制,但病毒 DNA 合成没有受到显著影响。有趣的是,FoxO1 的耗尽或过表达对病毒早期/晚期转录物的表达有显著影响。FoxO1 被发现与病毒复制隔间的 pUL44 蛋白亚基共定位,而与 DNA 没有直接关联。本研究强调了 FoxO 如何增强 HCMV 基因转录和病毒复制以促进感染。

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本文引用的文献

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Proc Natl Acad Sci U S A. 2020 Aug 4;117(31):18764-18770. doi: 10.1073/pnas.2002651117. Epub 2020 Jul 21.
2
FoxO1 and FoxA1/2 form a complex on DNA and cooperate to open chromatin at insulin-regulated genes.FoxO1与FoxA1/2在DNA上形成复合物,并协同作用以打开胰岛素调节基因处的染色质。
Biochem Cell Biol. 2019 Apr;97(2):118-129. doi: 10.1139/bcb-2018-0104. Epub 2018 Aug 24.
3
Characterization of the direct targets of FOXO transcription factors throughout evolution.
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bioRxiv. 2023 Apr 17:2023.04.17.537203. doi: 10.1101/2023.04.17.537203.
FOXO转录因子在整个进化过程中的直接靶标的表征。
Aging Cell. 2016 Aug;15(4):673-85. doi: 10.1111/acel.12479. Epub 2016 Apr 8.
4
Loss of Interdependent Binding by the FoxO1 and FoxA1/A2 Forkhead Transcription Factors Culminates in Perturbation of Active Chromatin Marks and Binding of Transcriptional Regulators at Insulin-sensitive Genes.FoxO1和FoxA1/A2叉头转录因子相互依赖结合的丧失最终导致活性染色质标记的紊乱以及转录调节因子在胰岛素敏感基因上的结合。
J Biol Chem. 2016 Apr 15;291(16):8848-61. doi: 10.1074/jbc.M115.677583. Epub 2016 Feb 29.
5
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