HIV 潜伏期。特定的 HIV 整合位点与受感染细胞的克隆扩增和持续存在有关。
HIV latency. Specific HIV integration sites are linked to clonal expansion and persistence of infected cells.
机构信息
HIV Drug Resistance Program, National Cancer Institute, Frederick, MD 21702, USA.
Leidos Biomedical Research, Frederick, MD 21702, USA.
出版信息
Science. 2014 Jul 11;345(6193):179-83. doi: 10.1126/science.1254194. Epub 2014 Jun 26.
Abstract
The persistence of HIV-infected cells in individuals on suppressive combination antiretroviral therapy (cART) presents a major barrier for curing HIV infections. HIV integrates its DNA into many sites in the host genome; we identified 2410 integration sites in peripheral blood lymphocytes of five infected individuals on cART. About 40% of the integrations were in clonally expanded cells. Approximately 50% of the infected cells in one patient were from a single clone, and some clones persisted for many years. There were multiple independent integrations in several genes, including MKL2 and BACH2; many of these integrations were in clonally expanded cells. Our findings show that HIV integration sites can play a critical role in expansion and persistence of HIV-infected cells.
摘要
在接受抑制性联合抗逆转录病毒疗法 (cART) 的个体中，HIV 感染细胞的持续存在是治愈 HIV 感染的主要障碍。HIV 将其 DNA 整合到宿主基因组的许多位点中；我们在五名接受 cART 的感染个体的外周血淋巴细胞中鉴定出 2410 个整合位点。大约 40%的整合发生在克隆扩增的细胞中。大约 50%的一个患者的感染细胞来自一个单一的克隆，一些克隆持续了很多年。在包括 MKL2 和 BACH2 在内的几个基因中存在多个独立的整合，其中许多整合发生在克隆扩增的细胞中。我们的研究结果表明，HIV 整合位点可能在 HIV 感染细胞的扩增和持续存在中发挥关键作用。
相似文献
1
HIV latency. Specific HIV integration sites are linked to clonal expansion and persistence of infected cells.HIV 潜伏期。特定的 HIV 整合位点与受感染细胞的克隆扩增和持续存在有关。
Science. 2014 Jul 11;345(6193):179-83. doi: 10.1126/science.1254194. Epub 2014 Jun 26.
2
HIV/AIDS. Persistence by proliferation?艾滋病毒/艾滋病。通过增殖实现持续存在？
Science. 2014 Jul 11;345(6193):143-4. doi: 10.1126/science.1257426.
3
Recurrent HIV-1 integration at the BACH2 locus in resting CD4+ T cell populations during effective highly active antiretroviral therapy.在有效的高效抗逆转录病毒治疗期间，静止CD4 + T细胞群体中HIV-1在BACH2基因座处的反复整合。
J Infect Dis. 2007 Mar 1;195(5):716-25. doi: 10.1086/510915. Epub 2007 Jan 18.
4
The role of integration and clonal expansion in HIV infection: live long and prosper.整合与克隆性扩张在 HIV 感染中的作用：生生不息。
Retrovirology. 2018 Oct 23;15(1):71. doi: 10.1186/s12977-018-0448-8.
5
Dynamics and mechanisms of clonal expansion of HIV-1-infected cells in a humanized mouse model.在人源化小鼠模型中 HIV-1 感染细胞的克隆扩增的动力学和机制。
Sci Rep. 2017 Jul 31;7(1):6913. doi: 10.1038/s41598-017-07307-4.
6
Early Emergence and Long-Term Persistence of HIV-Infected T-Cell Clones in Children.儿童体内受 HIV 感染的 T 细胞克隆的早期出现和长期持续存在。
mBio. 2021 Apr 8;12(2):e00568-21. doi: 10.1128/mBio.00568-21.
7
Clonal Expansion of Human Immunodeficiency Virus-Infected Cells and Human Immunodeficiency Virus Persistence During Antiretroviral Therapy.抗逆转录病毒治疗期间人类免疫缺陷病毒感染细胞的克隆扩增及人类免疫缺陷病毒持续存在
J Infect Dis. 2017 Mar 15;215(suppl_3):S119-S127. doi: 10.1093/infdis/jiw636.
8
HIV Integration Site Analysis of Cellular Models of HIV Latency with a Probe-Enriched Next-Generation Sequencing Assay.使用探针富集下一代测序分析法对HIV潜伏细胞模型进行HIV整合位点分析。
J Virol. 2016 Apr 14;90(9):4511-4519. doi: 10.1128/JVI.01617-15. Print 2016 May.
9
The Clonal Expansion Dynamics of the HIV-1 Reservoir: Mechanisms of Integration Site-Dependent Proliferation and HIV-1 Persistence.HIV-1 储库的克隆扩增动力学：整合位点依赖性增殖和 HIV-1 持续存在的机制。
Viruses. 2021 Sep 17;13(9):1858. doi: 10.3390/v13091858.
10
Clonal expansion of SIV-infected cells in macaques on antiretroviral therapy is similar to that of HIV-infected cells in humans.在抗逆转录病毒治疗的猕猴中，受 SIV 感染的细胞的克隆扩增与受 HIV 感染的人类细胞的克隆扩增相似。
PLoS Pathog. 2019 Jul 10;15(7):e1007869. doi: 10.1371/journal.ppat.1007869. eCollection 2019 Jul.
引用本文的文献
1
HIV-1 RNA in Large and Small Plasma Extracellular Vesicles: A Novel Parameter for Monitoring Immune Activation and Virological Failure.大小血浆细胞外囊泡中的HIV-1 RNA：监测免疫激活和病毒学失败的新参数。
J Med Virol. 2025 Sep;97(9):e70574. doi: 10.1002/jmv.70574.
2
Impacts of immune checkpoint inhibitors use on the HIV reservoir are linked to provirus sequences but not integration sites.免疫检查点抑制剂的使用对HIV储存库的影响与前病毒序列有关，而与整合位点无关。
Sci Rep. 2025 Aug 28;15(1):31726. doi: 10.1038/s41598-025-15349-2.
3
Transcription factor BACH2 shapes tissue-resident memory T cell programs to promote HIV-1 persistence.转录因子BACH2塑造组织驻留记忆T细胞程序以促进HIV-1持续存在。
Immunity. 2025 Aug 16. doi: 10.1016/j.immuni.2025.07.022.
4
Aquarius helicase facilitates HIV-1 integration into R-loop enriched genomic regions.水瓶座解旋酶促进HIV-1整合到富含R环的基因组区域。
Nat Microbiol. 2025 Aug 20. doi: 10.1038/s41564-025-02089-2.
5
From network biology to immunity: potential longitudinal biomarkers for targeting the network topology of the HIV reservoir.从网络生物学到免疫：用于靶向HIV储存库网络拓扑结构的潜在纵向生物标志物。
J Transl Med. 2025 Aug 13;23(1):906. doi: 10.1186/s12967-025-06919-z.
6
Proviruses in CD4 T cells reactive to autologous antigens contribute to nonsuppressible HIV-1 viremia.对自身抗原产生反应的CD4 T细胞中的前病毒会导致无法抑制的HIV-1病毒血症。
Sci Transl Med. 2025 Aug 13;17(811):eadu4643. doi: 10.1126/scitranslmed.adu4643.
7
HIV Integration into the PTEN Gene and Its Tumor Microenvironment Implications for Lung Cancer.HIV整合入PTEN基因及其对肺癌肿瘤微环境的影响
Curr Oncol. 2025 Jul 4;32(7):389. doi: 10.3390/curroncol32070389.
8
Biosafety considerations triggered by genome-editing technologies.基因组编辑技术引发的生物安全考量。
Biosaf Health. 2025 May 13;7(3):141-151. doi: 10.1016/j.bsheal.2025.05.003. eCollection 2025 Jun.
9
Identification of initial sites of SIV rebound after treatment cessation.确定治疗停止后SIV反弹的初始位点。
Res Sq. 2025 Jul 11:rs.3.rs-6814218. doi: 10.21203/rs.3.rs-6814218/v1.
10
Development and validation of HIV SMRTcap for the characterization of HIV-1 reservoirs across tissues and subtypes.用于表征跨组织和亚型的HIV-1储存库的HIV SMRTcap的开发与验证。
bioRxiv. 2025 May 5:2025.05.01.651657. doi: 10.1101/2025.05.01.651657.
本文引用的文献
1
Lack of detectable HIV-1 molecular evolution during suppressive antiretroviral therapy.在抗逆转录病毒疗法抑制病毒期间未检测到HIV-1分子进化。
PLoS Pathog. 2014 Mar 20;10(3):e1004010. doi: 10.1371/journal.ppat.1004010. eCollection 2014 Mar.
2
Enhancers are major targets for murine leukemia virus vector integration.增强子是鼠白血病病毒载体整合的主要靶点。
J Virol. 2014 Apr;88(8):4504-13. doi: 10.1128/JVI.00011-14. Epub 2014 Feb 5.
3
Lifespan of effector memory CD4+ T cells determined by replication-incompetent integrated HIV-1 provirus.由无复制能力的整合型HIV-1前病毒决定的效应记忆CD4+ T细胞的寿命。
AIDS. 2014 May 15;28(8):1091-9. doi: 10.1097/QAD.0000000000000223.
4
A genome-wide regulatory network identifies key transcription factors for memory CD8⁺ T-cell development.全基因组调控网络鉴定记忆性 CD8+T 细胞发育的关键转录因子。
Nat Commun. 2013;4:2830. doi: 10.1038/ncomms3830.
5
The HIV-1 reservoir in eight patients on long-term suppressive antiretroviral therapy is stable with few genetic changes over time.长期接受抑制性抗逆转录病毒疗法的 8 名患者的 HIV-1 储存库随时间推移基本稳定，遗传变化较少。
Proc Natl Acad Sci U S A. 2013 Dec 17;110(51):E4987-96. doi: 10.1073/pnas.1308313110. Epub 2013 Nov 25.
6
Replication-competent noninduced proviruses in the latent reservoir increase barrier to HIV-1 cure.潜伏库中具有复制能力的非诱导前病毒增加了 HIV-1 治愈的障碍。
Cell. 2013 Oct 24;155(3):540-51. doi: 10.1016/j.cell.2013.09.020.
7
Single cell analysis of lymph node tissue from HIV-1 infected patients reveals that the majority of CD4+ T-cells contain one HIV-1 DNA molecule.对感染 HIV-1 的患者的淋巴结组织进行单细胞分析显示，大多数 CD4+T 细胞中含有一个 HIV-1 DNA 分子。
PLoS Pathog. 2013;9(6):e1003432. doi: 10.1371/journal.ppat.1003432. Epub 2013 Jun 20.
8
Presence of C11orf95-MKL2 fusion is a consistent finding in chondroid lipomas: a study of eight cases.C11orf95-MKL2 融合的存在是软骨样脂肪瘤的一个一致发现：八项研究案例。
Histopathology. 2013 May;62(6):925-30. doi: 10.1111/his.12100. Epub 2013 Apr 12.
9
HIV pathogenesis: dynamics and genetics of viral populations and infected cells.HIV 发病机制：病毒群体和感染细胞的动力学和遗传学。
Cold Spring Harb Perspect Med. 2013 Jan 1;3(1):a012526. doi: 10.1101/cshperspect.a012526.
10
Towards an HIV cure: a global scientific strategy.迈向艾滋病治愈：全球科学策略。
Nat Rev Immunol. 2012 Jul 20;12(8):607-14. doi: 10.1038/nri3262.
Zotero 插件