• 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

逆转录病毒DNA整合：禽成髓细胞瘤病毒（ASLV）、人类免疫缺陷病毒（HIV）和小鼠白血病病毒（MLV）表现出不同的靶位点偏好。

Retroviral DNA integration: ASLV, HIV, and MLV show distinct target site preferences.

作者信息

Mitchell Rick S, Beitzel Brett F, Schroder Astrid R W, Shinn Paul, Chen Huaming, Berry Charles C, Ecker Joseph R, Bushman Frederic D

机构信息

Department of Microbiology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA.

出版信息

PLoS Biol. 2004 Aug;2(8):E234. doi: 10.1371/journal.pbio.0020234. Epub 2004 Aug 17.

DOI:10.1371/journal.pbio.0020234
PMID:15314653
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC509299/
Abstract

The completion of the human genome sequence has made possible genome-wide studies of retroviral DNA integration. Here we report an analysis of 3,127 integration site sequences from human cells. We compared retroviral vectors derived from human immunodeficiency virus (HIV), avian sarcoma-leukosis virus (ASLV), and murine leukemia virus (MLV). Effects of gene activity on integration targeting were assessed by transcriptional profiling of infected cells. Integration by HIV vectors, analyzed in two primary cell types and several cell lines, strongly favored active genes. An analysis of the effects of tissue-specific transcription showed that it resulted in tissue-specific integration targeting by HIV, though the effect was quantitatively modest. Chromosomal regions rich in expressed genes were favored for HIV integration, but these regions were found to be interleaved with unfavorable regions at CpG islands. MLV vectors showed a strong bias in favor of integration near transcription start sites, as reported previously. ASLV vectors showed only a weak preference for active genes and no preference for transcription start regions. Thus, each of the three retroviruses studied showed unique integration site preferences, suggesting that virus-specific binding of integration complexes to chromatin features likely guides site selection.

摘要

人类基因组序列的完成使得对逆转录病毒DNA整合进行全基因组研究成为可能。在此，我们报告了对来自人类细胞的3127个整合位点序列的分析。我们比较了源自人类免疫缺陷病毒（HIV）、禽肉瘤白血病病毒（ASLV）和鼠白血病病毒（MLV）的逆转录病毒载体。通过对感染细胞进行转录谱分析来评估基因活性对整合靶向的影响。在两种原代细胞类型和几种细胞系中分析的HIV载体整合，强烈倾向于活跃基因。对组织特异性转录作用的分析表明，这导致了HIV的组织特异性整合靶向，尽管这种作用在数量上较小。富含表达基因的染色体区域有利于HIV整合，但发现这些区域与CpG岛处的不利区域交错。如先前报道的那样，MLV载体表现出强烈偏向于在转录起始位点附近整合的倾向。ASLV载体仅对活跃基因表现出较弱的偏好，对转录起始区域没有偏好。因此，所研究的三种逆转录病毒中的每一种都表现出独特的整合位点偏好，这表明整合复合物与染色质特征的病毒特异性结合可能指导位点选择。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3bdc/509299/d92f43d3f7fc/pbio.0020234.g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3bdc/509299/99edea956f81/pbio.0020234.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3bdc/509299/c3c246744473/pbio.0020234.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3bdc/509299/354ba61e3304/pbio.0020234.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3bdc/509299/38ea8fe6f372/pbio.0020234.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3bdc/509299/45213c004e7a/pbio.0020234.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3bdc/509299/dd54487c27c1/pbio.0020234.g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3bdc/509299/d92f43d3f7fc/pbio.0020234.g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3bdc/509299/99edea956f81/pbio.0020234.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3bdc/509299/c3c246744473/pbio.0020234.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3bdc/509299/354ba61e3304/pbio.0020234.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3bdc/509299/38ea8fe6f372/pbio.0020234.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3bdc/509299/45213c004e7a/pbio.0020234.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3bdc/509299/dd54487c27c1/pbio.0020234.g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3bdc/509299/d92f43d3f7fc/pbio.0020234.g007.jpg

相似文献

1
Retroviral DNA integration: ASLV, HIV, and MLV show distinct target site preferences.逆转录病毒DNA整合：禽成髓细胞瘤病毒（ASLV）、人类免疫缺陷病毒（HIV）和小鼠白血病病毒（MLV）表现出不同的靶位点偏好。
PLoS Biol. 2004 Aug;2(8):E234. doi: 10.1371/journal.pbio.0020234. Epub 2004 Aug 17.
2
Human T-cell leukemia virus type 1 integration target sites in the human genome: comparison with those of other retroviruses.人类基因组中1型人类T细胞白血病病毒整合靶点：与其他逆转录病毒的比较。
J Virol. 2007 Jun;81(12):6731-41. doi: 10.1128/JVI.02752-06. Epub 2007 Apr 4.
3
Retroviral DNA integration: viral and cellular determinants of target-site selection.逆转录病毒DNA整合：靶位点选择的病毒和细胞决定因素
PLoS Pathog. 2006 Jun;2(6):e60. doi: 10.1371/journal.ppat.0020060. Epub 2006 Jun 23.
4
Proviruses with Long-Term Stable Expression Accumulate in Transcriptionally Active Chromatin Close to the Gene Regulatory Elements: Comparison of ASLV-, HIV- and MLV-Derived Vectors.具有长期稳定表达的前病毒在接近基因调控元件的转录活跃染色质中积累：ASLV、HIV 和 MLV 衍生载体的比较。
Viruses. 2018 Mar 8;10(3):116. doi: 10.3390/v10030116.
5
Transcription start regions in the human genome are favored targets for MLV integration.人类基因组中的转录起始区域是莫洛尼氏鼠白血病病毒（MLV）整合的有利靶点。
Science. 2003 Jun 13;300(5626):1749-51. doi: 10.1126/science.1083413.
6
Genome-wide analyses of avian sarcoma virus integration sites.禽肉瘤病毒整合位点的全基因组分析。
J Virol. 2004 Nov;78(21):11656-63. doi: 10.1128/JVI.78.21.11656-11663.2004.
7
Reduced genotoxicity of avian sarcoma leukosis virus vectors in rhesus long-term repopulating cells compared to standard murine retrovirus vectors.与标准鼠逆转录病毒载体相比，禽肉瘤白血病病毒载体在恒河猴长期重建造血细胞中的遗传毒性降低。
Mol Ther. 2008 Sep;16(9):1617-23. doi: 10.1038/mt.2008.135. Epub 2008 Jun 24.
8
Integration targeting by avian sarcoma-leukosis virus and human immunodeficiency virus in the chicken genome.禽肉瘤-白血病病毒和人类免疫缺陷病毒在鸡基因组中的整合靶向作用。
J Virol. 2005 Sep;79(18):12035-44. doi: 10.1128/JVI.79.18.12035-12044.2005.
9
Comparison of HIV-derived lentiviral and MLV-based gammaretroviral vector integration sites in primate repopulating cells.灵长类动物再增殖细胞中源自HIV的慢病毒载体和基于MLV的γ-逆转录病毒载体整合位点的比较。
Mol Ther. 2007 Jul;15(7):1356-65. doi: 10.1038/sj.mt.6300159. Epub 2007 Apr 17.
10
Genome-wide analysis of retroviral DNA integration.逆转录病毒DNA整合的全基因组分析。
Nat Rev Microbiol. 2005 Nov;3(11):848-58. doi: 10.1038/nrmicro1263.

引用本文的文献

1
Random Insertion Reporter Gimmicks Powered by Cut-and-Paste DNA Transposons.由剪切粘贴型DNA转座子驱动的随机插入报告基因技术
Biomedicines. 2025 Jul 9;13(7):1682. doi: 10.3390/biomedicines13071682.
2
The role of chromatin in retroviral preintegration complex function.染色质在逆转录病毒整合前复合体功能中的作用。
J Biol Chem. 2025 Jul 3;301(8):110440. doi: 10.1016/j.jbc.2025.110440.
3
Next-generation immunotherapeutic approaches for blood cancers: Exploring the efficacy of CAR-T and cancer vaccines.血液癌症的新一代免疫治疗方法：探索嵌合抗原受体T细胞（CAR-T）和癌症疫苗的疗效。

本文引用的文献

1
Unbiased mapping of transcription factor binding sites along human chromosomes 21 and 22 points to widespread regulation of noncoding RNAs.沿着人类21号和22号染色体对转录因子结合位点进行的无偏差定位表明非编码RNA受到广泛调控。
Cell. 2004 Feb 20;116(4):499-509. doi: 10.1016/s0092-8674(04)00127-8.
2
A BAC-based physical map of the chicken genome.基于细菌人工染色体的鸡基因组物理图谱。
Genome Res. 2003 Dec;13(12):2754-8. doi: 10.1101/gr.1499303.
3
The DNA sequence and analysis of human chromosome 6.人类6号染色体的DNA序列及分析
Exp Hematol Oncol. 2025 May 17;14(1):75. doi: 10.1186/s40164-025-00662-3.
4
Evolution of KoRV-A transcriptional silencing in wild koalas.野生考拉中考拉逆转录病毒A转录沉默的进化
Cell. 2025 Apr 17;188(8):2081-2093.e16. doi: 10.1016/j.cell.2025.02.006. Epub 2025 Mar 7.
5
Divergent populations of HIV-infected naive and memory CD4+ T cell clones in children on antiretroviral therapy.接受抗逆转录病毒治疗的儿童中，HIV感染的初始和记忆CD4 + T细胞克隆的不同群体。
J Clin Invest. 2025 Mar 6;135(9). doi: 10.1172/JCI188533. eCollection 2025 May 1.
6
Gene therapy then and now: A look back at changes in the field over the past 25 years.彼时与此时的基因疗法：回顾过去25年该领域的变化。
Mol Ther. 2025 May 7;33(5):1889-1902. doi: 10.1016/j.ymthe.2025.02.040. Epub 2025 Feb 28.
7
Characterization, Enrichment, and Computational Modeling of Cross-Linked Actin Networks in Transformed Trabecular Meshwork Cells.转化小梁网细胞中交联肌动蛋白网络的表征、富集及计算建模
Invest Ophthalmol Vis Sci. 2025 Feb 3;66(2):65. doi: 10.1167/iovs.66.2.65.
8
Analysis of Hepatic Lentiviral Vector Transduction: Implications for Preclinical Studies and Clinical Gene Therapy Protocols.肝内慢病毒载体转导分析：对临床前研究和临床基因治疗方案的启示。
Viruses. 2025 Feb 17;17(2):276. doi: 10.3390/v17020276.
9
Mechanisms of antigen-dependent resistance to chimeric antigen receptor (CAR)-T cell therapies.嵌合抗原受体（CAR）-T细胞疗法抗原依赖性耐药机制。
Cancer Cell Int. 2025 Feb 24;25(1):64. doi: 10.1186/s12935-025-03697-y.
10
Leveraging Vector-Based Gene Disruptions to Enhance CAR T-Cell Effectiveness.利用基于载体的基因破坏来增强嵌合抗原受体T细胞的有效性。
Cancers (Basel). 2025 Jan 24;17(3):383. doi: 10.3390/cancers17030383.
Nature. 2003 Oct 23;425(6960):805-11. doi: 10.1038/nature02055.
4
Targeting survival: integration site selection by retroviruses and LTR-retrotransposons.靶向生存：逆转录病毒和LTR逆转座子的整合位点选择
Cell. 2003 Oct 17;115(2):135-8. doi: 10.1016/s0092-8674(03)00760-8.
5
Global analysis of cellular transcription following infection with an HIV-based vector.基于HIV的载体感染后细胞转录的全局分析。
Mol Ther. 2003 Oct;8(4):674-87. doi: 10.1016/s1525-0016(03)00215-6.
6
The human transcriptome map reveals extremes in gene density, intron length, GC content, and repeat pattern for domains of highly and weakly expressed genes.人类转录组图谱揭示了高表达和低表达基因区域在基因密度、内含子长度、GC含量及重复模式方面的极端情况。
Genome Res. 2003 Sep;13(9):1998-2004. doi: 10.1101/gr.1649303. Epub 2003 Aug 12.
7
Transcription start regions in the human genome are favored targets for MLV integration.人类基因组中的转录起始区域是莫洛尼氏鼠白血病病毒（MLV）整合的有利靶点。
Science. 2003 Jun 13;300(5626):1749-51. doi: 10.1126/science.1083413.
8
Integration by design.设计集成
Proc Natl Acad Sci U S A. 2003 May 13;100(10):5586-8. doi: 10.1073/pnas.1031802100. Epub 2003 May 5.
9
Controlling integration specificity of a yeast retrotransposon.控制酵母逆转录转座子的整合特异性。
Proc Natl Acad Sci U S A. 2003 May 13;100(10):5891-5. doi: 10.1073/pnas.1036705100. Epub 2003 May 1.
10
Considering nuclear compartmentalization in the light of nuclear dynamics.从核动力学角度考虑核区室化。
Cell. 2003 Feb 21;112(4):403-6. doi: 10.1016/s0092-8674(03)00078-3.