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整合酶复合物亚基3敲低对成纤维细胞中1型单纯疱疹病毒的裂解感染影响极小。

Integrator Complex Subunit 3 Knockdown Has Minimal Effect on Lytic Herpes Simplex Virus Type-1 Infection in Fibroblast Cells.

作者信息

Heath Joseph R, Fromuth Daniel P, Dembowski Jill A

机构信息

Department of Biological Sciences, Duquesne University, Pittsburgh, Pennsylvania, United States.

出版信息

MicroPubl Biol. 2024 May 15;2024. doi: 10.17912/micropub.biology.001171. eCollection 2024.

DOI:10.17912/micropub.biology.001171
PMID:38817634
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11137619/
Abstract

Proteomic analysis of viral and cellular proteins that copurify with the herpes simplex virus type-1 (HSV-1) genome revealed that the cellular Integrator complex associates with viral DNA throughout infection. The Integrator complex plays a key role in the regulation of transcription of cellular coding and non-coding RNAs. We therefore predicted that it may regulate transcription of viral genes. Here, we demonstrate that knockdown of the Integrator complex subunit, Ints3, has minimal effect on HSV-1 infection. Despite reducing viral yield during low multiplicity infection, Ints3 knockdown had no effect on viral DNA replication, mRNA expression, or yield during high multiplicity infection.

摘要

对与1型单纯疱疹病毒(HSV-1)基因组共纯化的病毒和细胞蛋白进行蛋白质组学分析发现,在整个感染过程中,细胞整合酶复合物与病毒DNA相关联。整合酶复合物在细胞编码和非编码RNA转录调控中起关键作用。因此,我们推测它可能调控病毒基因的转录。在此,我们证明敲低整合酶复合物亚基Ints3对HSV-1感染影响极小。尽管在低 multiplicity 感染期间降低了病毒产量,但Ints3敲低对高 multiplicity 感染期间的病毒DNA复制、mRNA表达或产量没有影响。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6e5c/11137619/d342db3404eb/25789430-2024-micropub.biology.001171.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6e5c/11137619/d342db3404eb/25789430-2024-micropub.biology.001171.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6e5c/11137619/d342db3404eb/25789430-2024-micropub.biology.001171.jpg

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本文引用的文献

1
Proliferating cell nuclear antigen inhibitors block distinct stages of herpes simplex virus infection.增殖细胞核抗原抑制剂阻断单纯疱疹病毒感染的不同阶段。
PLoS Pathog. 2023 Jul 24;19(7):e1011539. doi: 10.1371/journal.ppat.1011539. eCollection 2023 Jul.
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A combinatorial approach to uncover an additional Integrator subunit.一种揭示额外 Integrator 亚基的组合方法。
Cell Rep. 2023 Mar 28;42(3):112244. doi: 10.1016/j.celrep.2023.112244. Epub 2023 Mar 14.
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Genomic regulation of transcription and RNA processing by the multitasking Integrator complex.
多任务整合复合物对转录和 RNA 加工的基因组调控。
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Structural basis of Integrator-mediated transcription regulation.整合子介导的转录调控的结构基础。
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Crystal structure of the INTS3/INTS6 complex reveals the functional importance of INTS3 dimerization in DSB repair.INTS3/INTS6复合物的晶体结构揭示了INTS3二聚化在DNA双链断裂修复中的功能重要性。
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Comparative proteomics identifies Schlafen 5 (SLFN5) as a herpes simplex virus restriction factor that suppresses viral transcription.比较蛋白质组学鉴定出 Schlafen 5(SLFN5)是一种单纯疱疹病毒限制因子,可抑制病毒转录。
Nat Microbiol. 2021 Feb;6(2):234-245. doi: 10.1038/s41564-020-00826-3. Epub 2021 Jan 11.
8
The Human Integrator Complex Facilitates Transcriptional Elongation by Endonucleolytic Cleavage of Nascent Transcripts.人类整合因子复合物通过内切核酸酶切割新生转录本促进转录延伸。
Cell Rep. 2020 Jul 21;32(3):107917. doi: 10.1016/j.celrep.2020.107917.
9
The Integrator Complex Attenuates Promoter-Proximal Transcription at Protein-Coding Genes.整合复合物可减弱蛋白质编码基因的启动子近端转录。
Mol Cell. 2019 Dec 5;76(5):738-752.e7. doi: 10.1016/j.molcel.2019.10.034.
10
Herpes simplex viral nucleoprotein creates a competitive transcriptional environment facilitating robust viral transcription and host shut off.单纯疱疹病毒核蛋白创造了一个竞争的转录环境,有利于病毒的高效转录和宿主关闭。
Elife. 2019 Oct 22;8:e51109. doi: 10.7554/eLife.51109.