KSHV RTA 通过利用宿主 E3 泛素连接酶复合物 RNF20/40 来驱动裂解性再激活。
KSHV RTA utilizes the host E3 ubiquitin ligase complex RNF20/40 to drive lytic reactivation.
机构信息
Department of Oral Biology, University of Florida College of Dentistry , Gainesville, Florida, USA.
UF Genetics Institute , Gainesville, Florida, USA.
出版信息
J Virol. 2023 Nov 30;97(11):e0138923. doi: 10.1128/jvi.01389-23. Epub 2023 Oct 27.
Abstract
Kaposi's sarcoma-associated herpesvirus (KSHV) is a cancer-causing human herpesvirus that establishes a persistent infection in humans. The lytic viral cycle plays a crucial part in lifelong infection as it is involved in the viral dissemination. The master regulator of the KSHV lytic replication cycle is the viral replication and transcription activator (RTA) protein, which is necessary and sufficient to push the virus from latency into the lytic phase. Thus, the identification of host factors utilized by RTA for controlling the lytic cycle can help to find novel targets that could be used for the development of antiviral therapies against KSHV. Using a proteomics approach, we have identified a novel interaction between RTA and the cellular E3 ubiquitin ligase complex RNF20/40, which we have shown to be necessary for promoting RTA-induced KSHV lytic cycle.
摘要
卡波西肉瘤相关疱疹病毒（KSHV）是一种致癌的人类疱疹病毒，可在人类中引发持续性感染。裂解病毒周期在终身感染中起着至关重要的作用，因为它涉及病毒的传播。KSHV 裂解复制周期的主要调节因子是病毒复制和转录激活剂（RTA）蛋白，它是将病毒从潜伏状态推向裂解阶段所必需且充分的。因此，鉴定 RTA 用于控制裂解周期的宿主因子有助于寻找可用于开发针对 KSHV 的抗病毒疗法的新靶标。我们使用蛋白质组学方法鉴定了 RTA 与细胞 E3 泛素连接酶复合物 RNF20/40 之间的新相互作用，我们已经表明该相互作用对于促进 RTA 诱导的 KSHV 裂解周期是必需的。
相似文献
1
KSHV RTA utilizes the host E3 ubiquitin ligase complex RNF20/40 to drive lytic reactivation.
J Virol. 2023 Nov 30;97(11):e0138923. doi: 10.1128/jvi.01389-23. Epub 2023 Oct 27.
2
KSHV RTA Induces Degradation of the Host Transcription Repressor ID2 To Promote the Viral Lytic Cycle.
J Virol. 2022 Jun 22;96(12):e0010122. doi: 10.1128/jvi.00101-22. Epub 2022 May 23.
3
Activation of Kaposi's sarcoma-associated herpesvirus (KSHV) by inhibitors of class III histone deacetylases: identification of sirtuin 1 as a regulator of the KSHV life cycle.
J Virol. 2014 Jun;88(11):6355-67. doi: 10.1128/JVI.00219-14. Epub 2014 Mar 26.
4
Analysis of the ubiquitin-modified proteome identifies novel host factors in Kaposi's sarcoma herpesvirus lytic reactivation.
J Virol. 2025 Jan 31;99(1):e0122424. doi: 10.1128/jvi.01224-24. Epub 2024 Dec 5.
5
ARID3B: a Novel Regulator of the Kaposi's Sarcoma-Associated Herpesvirus Lytic Cycle.
J Virol. 2016 Sep 29;90(20):9543-55. doi: 10.1128/JVI.03262-15. Print 2016 Oct 15.
6
Degradation of TRIM32 is induced by RTA for Kaposi's sarcoma-associated herpesvirus lytic replication.
J Virol. 2024 Jun 13;98(6):e0000524. doi: 10.1128/jvi.00005-24. Epub 2024 May 8.
7
NCOA2 promotes lytic reactivation of Kaposi's sarcoma-associated herpesvirus by enhancing the expression of the master switch protein RTA.
PLoS Pathog. 2019 Nov 21;15(11):e1008160. doi: 10.1371/journal.ppat.1008160. eCollection 2019 Nov.
8
Genome-Wide Identification of Direct RTA Targets Reveals Key Host Factors for Kaposi's Sarcoma-Associated Herpesvirus Lytic Reactivation.
J Virol. 2019 Feb 19;93(5). doi: 10.1128/JVI.01978-18. Print 2019 Mar 1.
9
Kaposi's sarcoma-associated herpesvirus K-Rta exhibits SUMO-targeting ubiquitin ligase (STUbL) like activity and is essential for viral reactivation.
PLoS Pathog. 2013;9(8):e1003506. doi: 10.1371/journal.ppat.1003506. Epub 2013 Aug 22.
10
IFI16 recruits HDAC1 and HDAC2 to deacetylate the Kaposi's sarcoma-associated herpesvirus (KSHV) latency-associated nuclear antigen (LANA), facilitating latency.
J Virol. 2025 Mar 18;99(3):e0154924. doi: 10.1128/jvi.01549-24. Epub 2025 Feb 10.
引用本文的文献
1
Viral pseudo-enzyme facilitates KSHV lytic replication via suppressing PFAS-mediated RTA deamidation.
Virol Sin. 2025 Jun;40(3):340-348. doi: 10.1016/j.virs.2025.04.005. Epub 2025 Apr 12.
2
Long-read transcriptomics of caviid gammaherpesvirus 1: compiling a comprehensive RNA atlas.
mSystems. 2025 Mar 18;10(3):e0167824. doi: 10.1128/msystems.01678-24. Epub 2025 Feb 27.
3
Long-read Transcriptomics of Caviid Gammaherpesvirus 1: Compiling a Comprehensive RNA Atlas.
bioRxiv. 2024 Dec 13:2024.12.11.627975. doi: 10.1101/2024.12.11.627975.
4
Hypoxic reactivation of Kaposi's sarcoma associated herpesvirus.
Cell Insight. 2024 Sep 7;3(6):100200. doi: 10.1016/j.cellin.2024.100200. eCollection 2024 Dec.
5
Conserved linear motif within the immediate early protein ORF45 promotes its engagement with KSHV lytic cycle-promoting forkhead transcription factors, FOXK1 and FOXK2.
J Virol. 2024 Oct 22;98(10):e0088624. doi: 10.1128/jvi.00886-24. Epub 2024 Sep 17.
6
ORF48 is required for optimal lytic replication of Kaposi's sarcoma-associated herpesvirus.
PLoS Pathog. 2024 Aug 26;20(8):e1012081. doi: 10.1371/journal.ppat.1012081. eCollection 2024 Aug.
7
Genome-Wide Transcriptional Roles of KSHV Viral Interferon Regulatory Factors in Oral Epithelial Cells.
Viruses. 2024 May 25;16(6):846. doi: 10.3390/v16060846.
8
Degradation of TRIM32 is induced by RTA for Kaposi's sarcoma-associated herpesvirus lytic replication.
J Virol. 2024 Jun 13;98(6):e0000524. doi: 10.1128/jvi.00005-24. Epub 2024 May 8.
本文引用的文献
1
KSHV transactivator-derived small peptide traps coactivators to attenuate MYC and inhibits leukemia and lymphoma cell growth.
Commun Biol. 2021 Dec 2;4(1):1330. doi: 10.1038/s42003-021-02853-0.
2
Epigenetic factor siRNA screen during primary KSHV infection identifies novel host restriction factors for the lytic cycle of KSHV.
PLoS Pathog. 2020 Jan 10;16(1):e1008268. doi: 10.1371/journal.ppat.1008268. eCollection 2020 Jan.
3
NCOA2 promotes lytic reactivation of Kaposi's sarcoma-associated herpesvirus by enhancing the expression of the master switch protein RTA.
PLoS Pathog. 2019 Nov 21;15(11):e1008160. doi: 10.1371/journal.ppat.1008160. eCollection 2019 Nov.
4
A herpesvirus transactivator and cellular POU proteins extensively regulate DNA binding of the host Notch signaling protein RBP-Jκ to the virus genome.
J Biol Chem. 2019 Aug 30;294(35):13073-13092. doi: 10.1074/jbc.RA118.007331. Epub 2019 Jul 15.
5
KSHV lytic proteins K-RTA and K8 bind to cellular and viral chromatin to modulate gene expression.
PLoS One. 2019 Apr 18;14(4):e0215394. doi: 10.1371/journal.pone.0215394. eCollection 2019.
6
Metascape provides a biologist-oriented resource for the analysis of systems-level datasets.
Nat Commun. 2019 Apr 3;10(1):1523. doi: 10.1038/s41467-019-09234-6.
7
RNF20/40-mediated eEF1BδL monoubiquitylation stimulates transcription of heat shock-responsive genes.
Nucleic Acids Res. 2019 Apr 8;47(6):2840-2855. doi: 10.1093/nar/gkz006.
8
Genome-Wide Identification of Direct RTA Targets Reveals Key Host Factors for Kaposi's Sarcoma-Associated Herpesvirus Lytic Reactivation.
J Virol. 2019 Feb 19;93(5). doi: 10.1128/JVI.01978-18. Print 2019 Mar 1.
9
Inhibition of the lytic cycle of Kaposi's sarcoma-associated herpesvirus by cohesin factors following de novo infection.
Virology. 2017 Dec;512:25-33. doi: 10.1016/j.virol.2017.09.001.
10
Kaposi's Sarcoma-Associated Herpesvirus Hijacks RNA Polymerase II To Create a Viral Transcriptional Factory.
J Virol. 2017 May 12;91(11). doi: 10.1128/JVI.02491-16. Print 2017 Jun 1.
Zotero 插件