• 文献检索
  • 文档翻译
  • 深度研究
  • 学术资讯
  • Suppr Zotero 插件Zotero 插件
  • 邀请有礼
  • 套餐&价格
  • 历史记录
应用&插件
Suppr Zotero 插件Zotero 插件浏览器插件Mac 客户端Windows 客户端微信小程序
定价
高级版会员购买积分包购买API积分包
服务
文献检索文档翻译深度研究API 文档MCP 服务
关于我们
关于 Suppr公司介绍联系我们用户协议隐私条款
关注我们

Suppr 超能文献

核心技术专利：CN118964589B侵权必究
粤ICP备2023148730 号-1Suppr @ 2026

文献检索

告别复杂PubMed语法，用中文像聊天一样搜索，搜遍4000万医学文献。AI智能推荐，让科研检索更轻松。

立即免费搜索

文件翻译

保留排版，准确专业，支持PDF/Word/PPT等文件格式，支持 12+语言互译。

免费翻译文档

深度研究

AI帮你快速写综述，25分钟生成高质量综述，智能提取关键信息，辅助科研写作。

立即免费体验

HCMV miR-US22 下调 EGR-1 调节 CD34+造血祖细胞增殖和病毒激活。

HCMV miR-US22 down-regulation of EGR-1 regulates CD34+ hematopoietic progenitor cell proliferation and viral reactivation.

机构信息

Vaccine and Gene Therapy Institute, Oregon Health & Science University, Beaverton, Oregon, United States of America.

Department of Immunobiology, BIO5 Institute, University of Arizona, Tucson, Arizona, United States of America.

出版信息

PLoS Pathog. 2019 Nov 14;15(11):e1007854. doi: 10.1371/journal.ppat.1007854. eCollection 2019 Nov.

DOI:10.1371/journal.ppat.1007854
PMID:31725809
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6855405/
Abstract

Reactivation of latent Human Cytomegalovirus (HCMV) in CD34+ hematopoietic progenitor cells (HPCs) is closely linked to hematopoiesis. Viral latency requires maintenance of the progenitor cell quiescence, while reactivation initiates following mobilization of HPCs to the periphery and differentiation into CD14+ macrophages. Early growth response gene 1 (EGR-1) is a transcription factor activated by Epidermal growth factor receptor (EGFR) signaling that is essential for the maintenance of CD34+ HPC self-renewal in the bone marrow niche. Down-regulation of EGR-1 results in mobilization and differentiation of CD34+ HPC from the bone marrow to the periphery. In the current study we demonstrate that the transcription factor EGR-1 is directly targeted for down-regulation by HCMV miR-US22 that results in decreased proliferation of CD34+ HPCs and a decrease in total hematopoietic colony formation. We also show that an HCMV miR-US22 mutant fails to reactivate in CD34+ HPCs, indicating that expression of EGR-1 inhibits viral reactivation. Since EGR-1 promotes CD34+ HPC self-renewal in the bone marrow niche, HCMV miR-US22 down-regulation of EGR-1 is a necessary step to block HPC self-renewal and proliferation to induce a cellular differentiation pathway necessary to promote reactivation of virus.

摘要

潜伏的人类巨细胞病毒 (HCMV) 在 CD34+造血祖细胞 (HPC) 中的重新激活与造血密切相关。病毒潜伏期需要维持祖细胞静止，而在 HPC 动员到外周并分化为 CD14+巨噬细胞后，重新激活就会开始。早期生长反应基因 1 (EGR-1) 是一种转录因子，受表皮生长因子受体 (EGFR) 信号激活，对于维持骨髓龛中 CD34+HPC 的自我更新至关重要。EGR-1 的下调会导致 CD34+HPC 从骨髓动员到外周。在本研究中，我们证明转录因子 EGR-1 是由 HCMV miR-US22 直接下调的靶标，导致 CD34+HPC 的增殖减少和总造血集落形成减少。我们还表明，HCMV miR-US22 突变体不能在 CD34+HPC 中重新激活，表明 EGR-1 的表达抑制病毒重新激活。由于 EGR-1 促进骨髓龛中 CD34+HPC 的自我更新，因此 HCMV miR-US22 下调 EGR-1 是阻止 HPC 自我更新和增殖以诱导促进病毒重新激活所需的细胞分化途径的必要步骤。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e792/6855405/9ba87a1ffae5/ppat.1007854.g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e792/6855405/d286e504f3f7/ppat.1007854.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e792/6855405/a49133e7e9e0/ppat.1007854.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e792/6855405/b3b630917a6e/ppat.1007854.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e792/6855405/430e3450cc6d/ppat.1007854.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e792/6855405/f0bbcbbd252f/ppat.1007854.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e792/6855405/31341a75d294/ppat.1007854.g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e792/6855405/f07d17775f22/ppat.1007854.g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e792/6855405/9ba87a1ffae5/ppat.1007854.g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e792/6855405/d286e504f3f7/ppat.1007854.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e792/6855405/a49133e7e9e0/ppat.1007854.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e792/6855405/b3b630917a6e/ppat.1007854.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e792/6855405/430e3450cc6d/ppat.1007854.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e792/6855405/f0bbcbbd252f/ppat.1007854.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e792/6855405/31341a75d294/ppat.1007854.g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e792/6855405/f07d17775f22/ppat.1007854.g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e792/6855405/9ba87a1ffae5/ppat.1007854.g008.jpg

相似文献

1
HCMV miR-US22 down-regulation of EGR-1 regulates CD34+ hematopoietic progenitor cell proliferation and viral reactivation.HCMV miR-US22 下调 EGR-1 调节 CD34+造血祖细胞增殖和病毒激活。
PLoS Pathog. 2019 Nov 14;15(11):e1007854. doi: 10.1371/journal.ppat.1007854. eCollection 2019 Nov.
2
Human Cytomegalovirus US28 Ligand Binding Activity Is Required for Latency in CD34 Hematopoietic Progenitor Cells and Humanized NSG Mice.人巨细胞病毒 US28 配体结合活性是潜伏在 CD34 造血祖细胞和人源化 NSG 小鼠中所必需的。
mBio. 2019 Aug 20;10(4):e01889-19. doi: 10.1128/mBio.01889-19.
3
Human Cytomegalovirus miR-US25-1 Targets the GTPase RhoA To Inhibit CD34 Hematopoietic Progenitor Cell Proliferation To Maintain the Latent Viral Genome.人类巨细胞病毒 miR-US25-1 靶向 GTPase RhoA 以抑制 CD34 造血祖细胞增殖，从而维持潜伏病毒基因组。
mBio. 2021 Apr 6;12(2):e00621-21. doi: 10.1128/mBio.00621-21.
4
Human Cytomegalovirus Requires Epidermal Growth Factor Receptor Signaling To Enter and Initiate the Early Steps in the Establishment of Latency in CD34 Human Progenitor Cells.人巨细胞病毒需要表皮生长因子受体信号传导才能进入并启动在CD34人祖细胞中建立潜伏感染的早期步骤。
J Virol. 2017 Feb 14;91(5). doi: 10.1128/JVI.01206-16. Print 2017 Mar 1.
5
Human Cytomegalovirus Encodes a Novel FLT3 Receptor Ligand Necessary for Hematopoietic Cell Differentiation and Viral Reactivation.人类巨细胞病毒编码一种新型 FLT3 受体配体，对于造血细胞分化和病毒激活是必需的。
mBio. 2018 Apr 24;9(2):e00682-18. doi: 10.1128/mBio.00682-18.
6
CD34 Hematopoietic Progenitor Cell Subsets Exhibit Differential Ability To Maintain Human Cytomegalovirus Latency and Persistence.CD34 造血祖细胞亚群表现出维持人类巨细胞病毒潜伏和持续感染的不同能力。
J Virol. 2021 Jan 13;95(3). doi: 10.1128/JVI.02105-20.
7
Human Cytomegalovirus miR-US5-2 Downregulation of GAB1 Regulates Cellular Proliferation and Expression through Modulation of Epidermal Growth Factor Receptor Signaling Pathways.人类巨细胞病毒 miR-US5-2 下调 GAB1 通过调节表皮生长因子受体信号通路调节细胞增殖和表达。
mSphere. 2020 Aug 5;5(4):e00582-20. doi: 10.1128/mSphere.00582-20.
8
Human Cytomegalovirus miRNAs Regulate TGF-β to Mediate Myelosuppression while Maintaining Viral Latency in CD34 Hematopoietic Progenitor Cells.人巨细胞病毒 microRNA 通过调节 TGF-β 介导骨髓抑制，同时维持 CD34 造血祖细胞中的病毒潜伏。
Cell Host Microbe. 2020 Jan 8;27(1):104-114.e4. doi: 10.1016/j.chom.2019.11.013. Epub 2019 Dec 19.
9
Host signaling and EGR1 transcriptional control of human cytomegalovirus replication and latency.宿主信号和 EGR1 转录对人巨细胞病毒复制和潜伏的控制。
PLoS Pathog. 2019 Nov 14;15(11):e1008037. doi: 10.1371/journal.ppat.1008037. eCollection 2019 Nov.
10
Human Cytomegalovirus UL7, miR-US5-1, and miR-UL112-3p Inactivation of FOXO3a Protects CD34 Hematopoietic Progenitor Cells from Apoptosis.人类巨细胞病毒 UL7、miR-US5-1 和 miR-UL112-3p 使 FOXO3a 失活，从而保护 CD34 造血祖细胞免于凋亡。
mSphere. 2021 Jan 6;6(1):e00986-20. doi: 10.1128/mSphere.00986-20.

引用本文的文献

1
Cytomegalovirus latency-the sum of subtleties.巨细胞病毒潜伏——细微之处的总和
J Virol. 2025 Aug 19;99(8):e0066425. doi: 10.1128/jvi.00664-25. Epub 2025 Jul 30.
2
Viral microRNA regulation of Akt is necessary for reactivation of Human Cytomegalovirus from latency in CD34+ hematopoietic progenitor cells and humanized mice.病毒微小RNA对Akt的调控对于人巨细胞病毒在CD34 +造血祖细胞和人源化小鼠中从潜伏状态重新激活是必要的。
PLoS Pathog. 2024 Dec 11;20(12):e1012285. doi: 10.1371/journal.ppat.1012285. eCollection 2024 Dec.
3
Human cytomegalovirus microRNAs: strategies for immune evasion and viral latency.

本文引用的文献

1
Host signaling and EGR1 transcriptional control of human cytomegalovirus replication and latency.宿主信号和 EGR1 转录对人巨细胞病毒复制和潜伏的控制。
PLoS Pathog. 2019 Nov 14;15(11):e1008037. doi: 10.1371/journal.ppat.1008037. eCollection 2019 Nov.
2
HCMV latency: what regulates the regulators?巨细胞病毒潜伏：谁来调控调控者？
Med Microbiol Immunol. 2019 Aug;208(3-4):431-438. doi: 10.1007/s00430-019-00581-1. Epub 2019 Feb 14.
3
Epstein-Barr virus microRNAs regulate B cell receptor signal transduction and lytic reactivation.
人巨细胞病毒 microRNAs：免疫逃避和病毒潜伏的策略。
Arch Virol. 2024 Jul 6;169(8):157. doi: 10.1007/s00705-024-06080-w.
4
Hematopoietic stem cells and betaherpesvirus latency.造血干细胞与β疱疹病毒潜伏。
Front Cell Infect Microbiol. 2023 Jun 6;13:1189805. doi: 10.3389/fcimb.2023.1189805. eCollection 2023.
5
Liver X Receptor-Inducible Host E3 Ligase IDOL Targets a Human Cytomegalovirus Reactivation Determinant.肝 X 受体诱导的宿主 E3 连接酶 IDOL 靶向人类巨细胞病毒再激活决定因素。
J Virol. 2023 Jul 27;97(7):e0075823. doi: 10.1128/jvi.00758-23. Epub 2023 Jun 20.
6
Shaping the host cell environment with viral noncoding RNAs.利用病毒非编码 RNA 塑造宿主细胞环境。
Semin Cell Dev Biol. 2023 Sep 15;146:20-30. doi: 10.1016/j.semcdb.2022.12.008. Epub 2022 Dec 28.
7
Viral miRNA regulation of host gene expression.病毒 miRNA 对宿主基因表达的调控。
Semin Cell Dev Biol. 2023 Sep 15;146:2-19. doi: 10.1016/j.semcdb.2022.11.007. Epub 2022 Nov 30.
8
Early Transcriptional Changes of Adipose-Derived Stem Cells (ADSCs) in Cell Culture.脂肪来源干细胞（ADSCs）在细胞培养中的早期转录变化。
Medicina (Kaunas). 2022 Sep 9;58(9):1249. doi: 10.3390/medicina58091249.
9
Human Cytomegalovirus Induced Aberrant Expression of Non-coding RNAs.人巨细胞病毒诱导非编码RNA的异常表达。
Front Microbiol. 2022 Jun 13;13:918213. doi: 10.3389/fmicb.2022.918213. eCollection 2022.
10
MicroRNA Regulation of Human Herpesvirus Latency.微小 RNA 对人类疱疹病毒潜伏的调控。
Viruses. 2022 Jun 2;14(6):1215. doi: 10.3390/v14061215.
EB 病毒 microRNAs 调节 B 细胞受体信号转导和裂解再激活。
PLoS Pathog. 2019 Jan 7;15(1):e1007535. doi: 10.1371/journal.ppat.1007535. eCollection 2019 Jan.
4
HCMV miRNA Targets Reveal Important Cellular Pathways for Viral Replication, Latency, and Reactivation.人巨细胞病毒微小RNA靶标揭示病毒复制、潜伏及再激活的重要细胞途径
Noncoding RNA. 2018 Oct 22;4(4):29. doi: 10.3390/ncrna4040029.
5
Molecular Determinants and the Regulation of Human Cytomegalovirus Latency and Reactivation.人巨细胞病毒潜伏和再激活的分子决定因素与调控。
Viruses. 2018 Aug 20;10(8):444. doi: 10.3390/v10080444.
6
Human Cytomegalovirus UL135 Interacts with Host Adaptor Proteins To Regulate Epidermal Growth Factor Receptor and Reactivation from Latency.人巨细胞病毒 UL135 通过与宿主衔接蛋白相互作用来调节表皮生长因子受体并从潜伏状态中重新激活。
J Virol. 2018 Sep 26;92(20). doi: 10.1128/JVI.00919-18. Print 2018 Oct 15.
7
Human Cytomegalovirus Encodes a Novel FLT3 Receptor Ligand Necessary for Hematopoietic Cell Differentiation and Viral Reactivation.人类巨细胞病毒编码一种新型 FLT3 受体配体，对于造血细胞分化和病毒激活是必需的。
mBio. 2018 Apr 24;9(2):e00682-18. doi: 10.1128/mBio.00682-18.
8
Transcriptome-wide characterization of human cytomegalovirus in natural infection and experimental latency.转录组水平上人类巨细胞病毒在自然感染和实验潜伏中的特征分析。
Proc Natl Acad Sci U S A. 2017 Dec 5;114(49):E10586-E10595. doi: 10.1073/pnas.1710522114. Epub 2017 Nov 20.
9
Human Cytomegalovirus Induces Cellular and Humoral Virus-specific Immune Responses in Humanized BLT Mice.人巨细胞病毒在人源化 BLT 小鼠中诱导细胞和体液病毒特异性免疫应答。
Sci Rep. 2017 Apr 20;7(1):937. doi: 10.1038/s41598-017-01051-5.
10
Human Cytomegalovirus MicroRNAs miR-US5-1 and miR-UL112-3p Block Proinflammatory Cytokine Production in Response to NF-κB-Activating Factors through Direct Downregulation of IKKα and IKKβ.人巨细胞病毒微小RNA miR-US5-1和miR-UL112-3p通过直接下调IKKα和IKKβ来阻断对NF-κB激活因子产生反应的促炎细胞因子的生成。
mBio. 2017 Mar 7;8(2):e00109-17. doi: 10.1128/mBio.00109-17.