ISG15：在 SARS-CoV-2 及其他病毒感染中的作用。
ISG15: its roles in SARS-CoV-2 and other viral infections.
机构信息
Cleveland Clinic Florida Research and Innovation Center, Port St. Lucie, FL, USA.
Cleveland Clinic Florida Research and Innovation Center, Port St. Lucie, FL, USA.
出版信息
Trends Microbiol. 2023 Dec;31(12):1262-1275. doi: 10.1016/j.tim.2023.07.006. Epub 2023 Aug 10.
Abstract
Interferon (IFN)-stimulated gene 15 (ISG15), a ubiquitin-like pleiotropic protein and one of the most abundant ISGs, has been studied extensively; however, its roles in SARS-CoV-2 and other viral infections have just begun to be elucidated. Emerging evidence suggests that ISG15 - either in its conjugated or unconjugated 'free' form - acts both intracellularly and extracellularly, and exerts anti- or pro-viral effects. To counteract ISG15's antiviral roles, viruses have evolved sophisticated tactics. Here, we discuss recent advances in ISG15's physiological functions as a post-translational modifier or 'cytokine-like' molecule during SARS-CoV-2 and other viral infections. Furthermore, we highlight the detailed mechanisms viruses use to block ISG15-dependent antiviral defenses. A comprehensive understanding of ISG15 biology in the context of virus infection may spur new therapeutic approaches for a range of viral infectious diseases.
摘要
干扰素（IFN）刺激基因 15（ISG15）是一种泛素样多功能蛋白，也是最丰富的 ISG 之一，已经得到了广泛的研究；然而，它在 SARS-CoV-2 和其他病毒感染中的作用才刚刚开始被阐明。新出现的证据表明，ISG15——无论是在其缀合的还是未缀合的“游离”形式下——都在细胞内和细胞外发挥作用，并产生抗病毒或促病毒作用。为了抵消 ISG15 的抗病毒作用，病毒已经进化出了复杂的策略。在这里，我们讨论了 ISG15 在 SARS-CoV-2 和其他病毒感染期间作为翻译后修饰物或“细胞因子样”分子的生理功能的最新进展。此外，我们强调了病毒用来阻断 ISG15 依赖性抗病毒防御的详细机制。全面了解病毒感染背景下的 ISG15 生物学可能会为一系列病毒性传染病提供新的治疗方法。
相似文献
1
ISG15: its roles in SARS-CoV-2 and other viral infections.ISG15：在 SARS-CoV-2 及其他病毒感染中的作用。
Trends Microbiol. 2023 Dec;31(12):1262-1275. doi: 10.1016/j.tim.2023.07.006. Epub 2023 Aug 10.
2
Coronaviral PLpro proteases and the immunomodulatory roles of conjugated versus free Interferon Stimulated Gene product-15 (ISG15).冠状病毒 PLpro 蛋白酶与结合型和游离型干扰素刺激基因产物 15（ISG15）的免疫调节作用。
Semin Cell Dev Biol. 2022 Dec;132:16-26. doi: 10.1016/j.semcdb.2022.06.005. Epub 2022 Jun 25.
3
Altered ISGylation drives aberrant macrophage-dependent immune responses during SARS-CoV-2 infection.SARS-CoV-2 感染期间，异常的 ISGylation 导致巨噬细胞依赖性免疫反应异常。
Nat Immunol. 2021 Nov;22(11):1416-1427. doi: 10.1038/s41590-021-01035-8. Epub 2021 Oct 18.
4
Free ISG15 and Protein ISGylation Emerging in SARS-CoV-2 Infection.新冠病毒感染中游离的 ISG15 和蛋白质的 ISG 化修饰。
Curr Drug Targets. 2022;23(7):686-691. doi: 10.2174/1389450123666220316094720.
5
ISG15 driven cellular responses to virus infection.ISG15 驱动的细胞对病毒感染的反应。
Biochem Soc Trans. 2022 Dec 16;50(6):1837-1846. doi: 10.1042/BST20220839.
6
SARS-CoV-2 papain-like protease inhibits ISGylation of the viral nucleocapsid protein to evade host anti-viral immunity.SARS-CoV-2 木瓜蛋白酶样蛋白酶抑制病毒核衣壳蛋白的 ISG 化，从而逃避宿主抗病毒免疫。
J Virol. 2024 Sep 17;98(9):e0085524. doi: 10.1128/jvi.00855-24. Epub 2024 Aug 9.
7
ISGylation of the SARS-CoV-2 N protein by HERC5 impedes N oligomerization and thereby viral RNA synthesis.HERC5 对 SARS-CoV-2 N 蛋白的 ISGylation 抑制了 N 蛋白寡聚化，从而抑制了病毒 RNA 的合成。
J Virol. 2024 Sep 17;98(9):e0086924. doi: 10.1128/jvi.00869-24. Epub 2024 Aug 28.
8
Viral Evasion of RIG-I-Like Receptor-Mediated Immunity through Dysregulation of Ubiquitination and ISGylation.病毒通过泛素化和 ISG 化失调逃避 RIG-I 样受体介导的免疫。
Viruses. 2021 Jan 26;13(2):182. doi: 10.3390/v13020182.
9
ISG15 Arg151 and the ISG15-conjugating enzyme UbE1L are important for innate immune control of Sindbis virus.ISG15的第151位精氨酸以及ISG15缀合酶UbE1L对辛德毕斯病毒的天然免疫控制很重要。
J Virol. 2009 Feb;83(4):1602-10. doi: 10.1128/JVI.01590-08. Epub 2008 Dec 10.
10
How ISG15 combats viral infection.ISG15 如何对抗病毒感染。
Virus Res. 2020 Sep;286:198036. doi: 10.1016/j.virusres.2020.198036. Epub 2020 May 31.
引用本文的文献
1
Peripheral transcriptional responses to experimental SARS-CoV-2 inoculation in North American elk cows and calves.北美麋鹿母牛和幼崽对实验性接种严重急性呼吸综合征冠状病毒2的外周转录反应。
BMC Genomics. 2025 Aug 28;26(1):781. doi: 10.1186/s12864-025-11956-5.
2
ISG-15, beyond its functions in the cell: a mini review.ISG-15在细胞外的功能：一篇综述
Cell Mol Life Sci. 2025 Jul 28;82(1):289. doi: 10.1007/s00018-025-05705-w.
3
Linking TLR-7 Signaling to Downregulation of Placental P-Glycoprotein: Implications for Fetal Drug Exposure.将Toll样受体7（TLR-7）信号传导与胎盘P-糖蛋白的下调联系起来：对胎儿药物暴露的影响。
Pharmaceutics. 2025 Jun 5;17(6):741. doi: 10.3390/pharmaceutics17060741.
4
PLpro Inhibitors as a Potential Treatment for COVID-19.PLpro抑制剂作为治疗新冠肺炎的潜在疗法
Biomedicines. 2025 Jun 10;13(6):1417. doi: 10.3390/biomedicines13061417.
5
Elevation of ISG15 promotes diabetic kidney disease by modulating renal tubular epithelial cell pyroptosis.ISG15的升高通过调节肾小管上皮细胞焦亡促进糖尿病肾病。
Clin Transl Med. 2025 Jun;15(6):e70337. doi: 10.1002/ctm2.70337.
6
Fucoidan Alleviates Porcine Epidemic Diarrhea Virus-Induced Intestinal Damage in Piglets by Enhancing Antioxidant Capacity and Modulating Arginine Metabolism.岩藻依聚糖通过增强抗氧化能力和调节精氨酸代谢减轻猪流行性腹泻病毒诱导的仔猪肠道损伤。
Animals (Basel). 2025 Mar 30;15(7):1001. doi: 10.3390/ani15071001.
7
MDA5 ISGylation is crucial for immune signaling to control viral replication and pathogenesis.黑色素瘤分化相关基因5（MDA5）的异戊二烯化修饰对于免疫信号传导以控制病毒复制和发病机制至关重要。
Proc Natl Acad Sci U S A. 2025 Apr 8;122(14):e2420190122. doi: 10.1073/pnas.2420190122. Epub 2025 Apr 4.
8
Design of quinoline SARS-CoV-2 papain-like protease inhibitors as oral antiviral drug candidates.喹啉类新型冠状病毒木瓜样蛋白酶抑制剂作为口服抗病毒候选药物的设计
Nat Commun. 2025 Feb 13;16(1):1604. doi: 10.1038/s41467-025-56902-x.
9
Multiorgan proteomic analysis of infected animal models predict potential host factors for chikungunya virus.感染动物模型的多器官蛋白质组学分析预测基孔肯雅病毒的潜在宿主因素。
MedComm (2020). 2025 Jan 3;6(1):e70013. doi: 10.1002/mco2.70013. eCollection 2025 Jan.
10
Beclin 1 prevents ISG15-mediated cytokine storms to secure fetal hematopoiesis and survival.Beclin 1可预防ISG15介导的细胞因子风暴，以确保胎儿造血及存活。
J Clin Invest. 2025 Feb 3;135(3):e177375. doi: 10.1172/JCI177375.
本文引用的文献
1
The diverse repertoire of ISG15: more intricate than initially thought.ISG15 的多样化功能：比最初想象的更为复杂。
Exp Mol Med. 2022 Nov;54(11):1779-1792. doi: 10.1038/s12276-022-00872-3. Epub 2022 Nov 1.
2
Free ISG15 inhibits Pseudorabies virus infection by positively regulating type I IFN signaling.游离的泛素样蛋白 ISG15 通过正向调控 I 型干扰素信号通路来抑制伪狂犬病毒感染。
PLoS Pathog. 2022 Oct 31;18(10):e1010921. doi: 10.1371/journal.ppat.1010921. eCollection 2022 Oct.
3
The E3 ubiquitin ligase ARIH1 promotes antiviral immunity and autoimmunity by inducing mono-ISGylation and oligomerization of cGAS.E3 泛素连接酶 ARIH1 通过诱导 cGAS 的单 ISG 化和寡聚化来促进抗病毒免疫和自身免疫。
Nat Commun. 2022 Oct 10;13(1):5973. doi: 10.1038/s41467-022-33671-5.
4
Early stimulated immune responses predict clinical disease severity in hospitalized COVID-19 patients.早期激发的免疫反应可预测住院COVID-19患者的临床疾病严重程度。
Commun Med (Lond). 2022 Sep 12;2:114. doi: 10.1038/s43856-022-00178-5. eCollection 2022.
5
Free ISG15 Inhibits the Replication of Peste des Petits Ruminants Virus by Breaking the Interaction of Nucleoprotein and Phosphoprotein.游离的泛素样修饰蛋白 15 通过打破核蛋白和磷蛋白的相互作用抑制小反刍兽疫病毒的复制。
Microbiol Spectr. 2022 Oct 26;10(5):e0103122. doi: 10.1128/spectrum.01031-22. Epub 2022 Aug 29.
6
ISG15 deficiency restricts HIV-1 infection.ISG15缺陷限制HIV-1感染。
PLoS Pathog. 2022 Mar 25;18(3):e1010405. doi: 10.1371/journal.ppat.1010405. eCollection 2022 Mar.
7
The immunology and immunopathology of COVID-19.新型冠状病毒肺炎的免疫学和免疫病理学。
Science. 2022 Mar 11;375(6585):1122-1127. doi: 10.1126/science.abm8108. Epub 2022 Mar 10.
8
The ubiquitin E3 ligase ARIH1 regulates hnRNP E1 protein stability, EMT and breast cancer progression.泛素E3连接酶ARIH1调节hnRNP E1蛋白稳定性、上皮-间质转化及乳腺癌进展。
Oncogene. 2022 Mar;41(12):1679-1690. doi: 10.1038/s41388-022-02199-9. Epub 2022 Jan 31.
9
Altered ISGylation drives aberrant macrophage-dependent immune responses during SARS-CoV-2 infection.SARS-CoV-2 感染期间，异常的 ISGylation 导致巨噬细胞依赖性免疫反应异常。
Nat Immunol. 2021 Nov;22(11):1416-1427. doi: 10.1038/s41590-021-01035-8. Epub 2021 Oct 18.
10
Possible future waves of SARS-CoV-2 infection generated by variants of concern with a range of characteristics.可能由具有不同特征的关注变体引发的 SARS-CoV-2 感染的未来波次。
Nat Commun. 2021 Sep 30;12(1):5730. doi: 10.1038/s41467-021-25915-7.
Zotero 插件