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疱疹病毒 EB 病毒去泛素化酶 BPLF1 在生产性感染期间调节拓扑异构酶 II 的活性。

The Epstein-Barr virus deubiquitinating enzyme BPLF1 regulates the activity of topoisomerase II during productive infection.

机构信息

Department of Cell and Molecular Biology, Karolinska Institutet, Stockholm, Sweden.

Department of Molecular Biology, Umeå Center for Microbial Research, Umeå University, Umeå, Sweden.

出版信息

PLoS Pathog. 2021 Sep 20;17(9):e1009954. doi: 10.1371/journal.ppat.1009954. eCollection 2021 Sep.

DOI:10.1371/journal.ppat.1009954
PMID:34543352
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8483405/
Abstract

Topoisomerases are essential for the replication of herpesviruses but the mechanisms by which the viruses hijack the cellular enzymes are largely unknown. We found that topoisomerase-II (TOP2) is a substrate of the Epstein-Barr virus (EBV) ubiquitin deconjugase BPLF1. BPLF1 co-immunoprecipitated and deubiquitinated TOP2, and stabilized SUMOylated TOP2 trapped in cleavage complexes (TOP2ccs), which halted the DNA damage response to TOP2-induced double strand DNA breaks and promoted cell survival. Induction of the productive virus cycle in epithelial and lymphoid cell lines carrying recombinant EBV encoding the active enzyme was accompanied by TOP2 deubiquitination, accumulation of TOP2ccs and resistance to Etoposide toxicity. The protective effect of BPLF1 was dependent on the expression of tyrosyl-DNA phosphodiesterase 2 (TDP2) that releases DNA-trapped TOP2 and promotes error-free DNA repair. These findings highlight a previously unrecognized function of BPLF1 in supporting a non-proteolytic pathway for TOP2ccs debulking that favors cell survival and virus production.

摘要

拓扑异构酶对于疱疹病毒的复制至关重要，但病毒劫持细胞酶的机制在很大程度上尚不清楚。我们发现拓扑异构酶 II（TOP2）是 Epstein-Barr 病毒（EBV）泛素去连接酶 BPLF1 的底物。BPLF1 与 TOP2 共免疫沉淀并去泛素化，稳定了 SUMO 化的 TOP2 被困在切割复合物（TOP2ccs）中，这阻止了 DNA 损伤反应对 TOP2 诱导的双链 DNA 断裂，并促进了细胞存活。在携带编码活性酶的重组 EBV 的上皮细胞系和淋巴样细胞系中诱导有性病毒周期伴随着 TOP2 去泛素化、TOP2ccs 的积累以及对依托泊苷毒性的抗性。BPLF1 的保护作用依赖于酪氨酸-DNA 磷酸二酯酶 2（TDP2）的表达，该酶释放 DNA 捕获的 TOP2 并促进无差错的 DNA 修复。这些发现强调了 BPLF1 在支持 TOP2ccs 去瘤的非蛋白水解途径中的先前未被认识的功能，该途径有利于细胞存活和病毒产生。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c08b/8483405/b8d74adc5584/ppat.1009954.g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c08b/8483405/2c224222c862/ppat.1009954.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c08b/8483405/f8622a68dba1/ppat.1009954.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c08b/8483405/39828b652886/ppat.1009954.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c08b/8483405/a9aa8d3519d0/ppat.1009954.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c08b/8483405/7092b495fe21/ppat.1009954.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c08b/8483405/7ccc018447da/ppat.1009954.g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c08b/8483405/b8d74adc5584/ppat.1009954.g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c08b/8483405/2c224222c862/ppat.1009954.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c08b/8483405/f8622a68dba1/ppat.1009954.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c08b/8483405/39828b652886/ppat.1009954.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c08b/8483405/a9aa8d3519d0/ppat.1009954.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c08b/8483405/7092b495fe21/ppat.1009954.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c08b/8483405/7ccc018447da/ppat.1009954.g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c08b/8483405/b8d74adc5584/ppat.1009954.g007.jpg

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2
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Sci Adv. 2020 Nov 13;6(46). doi: 10.1126/sciadv.aba6290. Print 2020 Nov.
3
Viral Ubiquitin and Ubiquitin-Like Deconjugases-Swiss Army Knives for Infection.
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Front Microbiol. 2024 Dec 5;15:1505191. doi: 10.3389/fmicb.2024.1505191. eCollection 2024.
4
Ubiquitin-Mediated Effects on Oncogenesis during EBV and KSHV Infection.泛素化对 EBV 和 KSHV 感染期间致癌作用的影响。
Viruses. 2024 Sep 26;16(10):1523. doi: 10.3390/v16101523.
5
Remodeling of the ribosomal quality control and integrated stress response by viral ubiquitin deconjugases.病毒泛素去连接酶对核糖体质量控制和综合应激反应的重塑作用。
Nat Commun. 2023 Dec 14;14(1):8315. doi: 10.1038/s41467-023-43946-0.
6
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7
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