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Free ISG15 and Protein ISGylation Emerging in SARS-CoV-2 Infection

Author(s): Angeles C. Tecalco Cruz*

Volume 23, Issue 7, 2022

Published on: 14 April, 2022

Page: [686 - 691] Pages: 6

DOI: 10.2174/1389450123666220316094720

Open Access Journals Promotions 2
Abstract

Interferon-simulated gene 15 (ISG15) belongs to the family of ubiquitin-like proteins. ISG15 acts as a cytokine and modifies proteins through ISGylation. This posttranslational modification has been associated with antiviral and immune response pathways. In addition, it is known that the genome of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) encodes proteases critical for viral replication. Consequently, these proteases are also central in the progression of coronavirus disease 2019 (COVID-19). Interestingly, the protease SARS-CoV-2-PLpro removes ISG15 from ISGylated proteins such as IRF3 and MDA5, affecting immune and antiviral defense from the host. Here, the implications of ISG15, ISGylation, and generation of SARS-CoV-2-PLpro inhibitors in SARS-CoV-2 infection are discussed.

Keywords: COVID-19, SARS-CoV-2, SCoV-PLpro, ISG15, ISGylation, protease.

« Previous Next »
[1]
Pinto BGG, Oliveira AER, Singh Y, et al. ACE2 expression is increased in the lungs of patients with comorbidities associated with severe COVID-19. J Infect Dis 2020; 222(4): 556-63.
[http://dx.doi.org/10.1093/infdis/jiaa332] [PMID: 32526012]
[2]
Franchini M, Bongiovanni G, Cruciani M. Mortality from COVID-19. Ann Ig 2021; 33(5): 521-3.
[http://dx.doi.org/10.7416/ai.2021.2451] [PMID: 34223866]
[3]
Gupta I, Rizeq B, Elkord E, Vranic S, Al Moustafa AE. SAR-CoV-2 infection and lung cancer: Potential therapeutic modalities. Cancers (Basel) 2020; 12(8): 1-21.
[http://dx.doi.org/10.3390/cancers12082186] [PMID: 32764454]
[4]
Bahranifard B, Mehdizadeh S, Hamidi A, et al. A review of neuroradiological abnormalities in patients with coronavirus disease 2019 (COVID-19). Neuroradiol J 2021; 19714009211029119714009211029177
[http://dx.doi.org/10.1177/19714009211029177] [PMID: 34224248]
[5]
Danics K, Forrest SL, Kapas I, et al. Neurodegenerative proteinopathies associated with neuroinfections. J Neural Transm (Vienna) 2021; 128(10): 1551-66.
[http://dx.doi.org/10.1007/s00702-021-02371-7] [PMID: 34223998]
[6]
Wang Y, Fan Y, Huang Y, et al. TRIM28 regulates SARS-CoV-2 cell entry by targeting ACE2. Cell Signal 2021; 85110064
[http://dx.doi.org/10.1016/j.cellsig.2021.110064] [PMID: 34146659]
[7]
Coperchini F, Ricci G, Croce L, et al. Modulation of ACE-2 mRNA by inflammatory cytokines in human thyroid cells: a pilot study. Endocrine 2021; 74(3): 638-45.
[http://dx.doi.org/10.1007/s12020-021-02807-w] [PMID: 34224085]
[8]
Scagnolari C, Bitossi C, Viscido A, et al. ACE2 expression is related to the interferon response in airway epithelial cells but is that functional for SARS-CoV-2 entry? Cytokine 2021; 140155430
[http://dx.doi.org/10.1016/j.cyto.2021.155430] [PMID: 33508651]
[9]
Ziegler CGK, Allon SJ, Nyquist SK, et al. HCA Lung Biological Network. SARS-CoV-2 receptor ACE2 is an interferon-stimulated gene in human airway epithelial cells and is detected in specific cell subsets across tissues. Cell 2020; 181(5): 1016-1035.e19.
[http://dx.doi.org/10.1016/j.cell.2020.04.035] [PMID: 32413319]
[10]
Lee MC, Chen YK, Tsai-Wu JJ, Hsu YJ, Lin BR. Zinc supplementation augments the suppressive effects of repurposed NF-B inhibitors on ACE2 expression in human lung cell lines. Life Sci 2021; 280119752
[http://dx.doi.org/10.1016/j.lfs.2021.119752] [PMID: 34171382]
[11]
Onabajo OO, Banday AR, Stanifer ML, et al. Interferons and viruses induce a novel truncated ACE2 isoform and not the full-length SARS-CoV-2 receptor. Nat Genet 2020; 52(12): 1283-93.
[http://dx.doi.org/10.1038/s41588-020-00731-9] [PMID: 33077916]
[12]
Samad A, Jafar T, Rafi JH. Identification of angiotensin-converting enzyme 2 (ACE2) protein as the potential biomarker in SARS-CoV-2 infection-related lung cancer using computational analyses. Genomics 2020; 112(6): 4912-23.
[http://dx.doi.org/10.1016/j.ygeno.2020.09.002] [PMID: 32916258]
[13]
Jorgovanovic D, Song M, Wang L, Zhang Y. Roles of IFN-; in tumor progression and regression: a review. Biomark Res 2020; 8: 49.
[http://dx.doi.org/10.1186/s40364-020-00228-x] [PMID: 33005420]
[14]
Castro F, Cardoso AP, Gonçalves RM, Serre K, Oliveira MJ. Interferon-gamma at the crossroads of tumor immune surveillance or evasion. Front Immunol 2018; 9: 847.
[http://dx.doi.org/10.3389/fimmu.2018.00847] [PMID: 29780381]
[15]
Mostafa AA, Codner D, Hirasawa K, et al. Activation of ER signaling differentially modulates IFN- induced HLA-class II expression in breast cancer cells. PLoS One 2014; 9(1)e87377
[http://dx.doi.org/10.1371/journal.pone.0087377] [PMID: 24475282]
[16]
Browne SK, Roesser JR, Zhu SZ, Ginder GD. Differential IFN- stimulation of HLA-A gene expression through CRM-1-dependent nuclear RNA export. J Immunol 2006; 177(12): 8612-9.
[http://dx.doi.org/10.4049/jimmunol.177.12.8612] [PMID: 17142760]
[17]
Cui XF, Imaizumi T, Yoshida H, Borden EC, Satoh K. Retinoic acid-inducible gene-I is induced by interferon- and regulates the expression of interferon- stimulated gene 15 in MCF-7 cells. Biochem Cell Biol 2004; 82(3): 401-5.
[http://dx.doi.org/10.1139/o04-041] [PMID: 15181474]
[18]
Imaizumi T, Yagihashi N, Hatakeyama M, et al. Expression of retinoic acid-inducible gene-I in vascular smooth muscle cells stimulated with interferon-&#947. Life Sci 2004; 75(10): 1171-80.
[http://dx.doi.org/10.1016/j.lfs.2004.01.030] [PMID: 15219805]
[19]
Imaizumi T, Hatakeyama M, Yamashita K, et al. Interferon- induces retinoic acid-inducible gene-I in endothelial cells. Endothelium 2004; 11(3-4): 169-73.
[http://dx.doi.org/10.1080/10623320490512156] [PMID: 15370293]
[20]
Tecalco-Cruz AC. Molecular pathways of interferon-stimulated gene 15: Implications in cancer. Curr Protein Pept Sci 2021; 22(1): 19-28.
[http://dx.doi.org/10.2174/1389203721999201208200747] [PMID: 33292152]
[21]
Fan JB, Zhang DE. ISG15 regulates IFN- immunity in human mycobacterial disease. Cell Res 2013; 23(2): 173-5.
[http://dx.doi.org/10.1038/cr.2012.133] [PMID: 22964713]
[22]
Swaim CD, Scott AF, Canadeo LA, Huibregtse JM. Extracellular ISG15 signals cytokine secretion through the LFA-1 integrin receptor. Mol Cell 2017; 68(3): 581-590.e5.
[http://dx.doi.org/10.1016/j.molcel.2017.10.003] [PMID: 29100055]
[23]
Swaim CD, Canadeo LA, Monte KJ, Khanna S, Lenschow DJ, Huibregtse JM. Modulation of extracellular ISG15 signaling by pathogens and viral effector proteins. Cell Rep 2020; 31(11)107772
[http://dx.doi.org/10.1016/j.celrep.2020.107772] [PMID: 32553163]
[24]
Padovan E, Terracciano L, Certa U, et al. Interferon stimulated gene 15 constitutively produced by melanoma cells induces e-cadherin expression on human dendritic cells. Cancer Res 2002; 62(12): 3453-8.
[PMID: 12067988]
[25]
Feng Q, Sekula D, Guo Y, et al. UBE1L causes lung cancer growth suppression by targeting cyclin D1. Mol Cancer Ther 2008; 7(12): 3780-8.
[http://dx.doi.org/10.1158/1535-7163.MCT-08-0753] [PMID: 19074853]
[26]
Sainz B Jr, Martín B, Tatari M, Heeschen C, Guerra S. ISG15 is a critical microenvironmental factor for pancreatic cancer stem cells. Cancer Res 2014; 74(24): 7309-20.
[http://dx.doi.org/10.1158/0008-5472.CAN-14-1354] [PMID: 25368022]
[27]
Chen RH, Du Y, Han P, et al. ISG15 predicts poor prognosis and promotes cancer stem cell phenotype in nasopharyngeal carcinoma. Oncotarget 2016; 7(13): 16910-22.
[http://dx.doi.org/10.18632/oncotarget.7626] [PMID: 26919245]
[28]
Desai SD, Haas AL, Wood LM, et al. Elevated expression of ISG15 in tumor cells interferes with the ubiquitin/26S proteasome pathway. Cancer Res 2006; 66(2): 921-8.
[http://dx.doi.org/10.1158/0008-5472.CAN-05-1123] [PMID: 16424026]
[29]
Wan XX, Chen HC, Khan MA, et al. ISG15 inhibits IFN--resistant liver cancer cell growth. BioMed Res Int 2013; 2013570909
[http://dx.doi.org/10.1155/2013/570909] [PMID: 24024201]
[30]
Lee JH, Bae JA, Lee JH, et al. Glycoprotein 90K, downregulated in advanced colorectal cancer tissues, interacts with CD9/CD82 and suppresses the Wnt/-catenin signal via ISGylation of -catenin. Gut 2010; 59(7): 907-17.
[http://dx.doi.org/10.1136/gut.2009.194068] [PMID: 20581239]
[31]
Villarroya-Beltri C, Baixauli F, Mittelbrunn M, et al. ISGylation controls exosome secretion by promoting lysosomal degradation of MVB proteins. Nat Commun 2016; 7: 13588.
[http://dx.doi.org/10.1038/ncomms13588] [PMID: 27882925]
[32]
Burks J, Reed RE, Desai SD. ISGylation governs the oncogenic function of Ki-Ras in breast cancer. Oncogene 2014; 33(6): 794-803.
[http://dx.doi.org/10.1038/onc.2012.633] [PMID: 23318454]
[33]
Jeon YJ, Choi JS, Lee JY, et al. ISG15 modification of filamin B negatively regulates the type I interferon-induced JNK signalling pathway. EMBO Rep 2009; 10(4): 374-80.
[http://dx.doi.org/10.1038/embor.2009.23] [PMID: 19270716]
[34]
Yuan H, Zhou W, Yang Y, Xue L, Liu L, Song Y. ISG15 promotes esophageal squamous cell carcinoma tumorigenesis via c-MET/Fyn/-catenin signaling pathway. Exp Cell Res 2018; 367(1): 47-55.
[http://dx.doi.org/10.1016/j.yexcr.2018.03.017] [PMID: 29555370]
[35]
Burks J, Reed RE, Desai SD. Free ISG15 triggers an antitumor immune response against breast cancer: a new perspective. Oncotarget 2015; 6(9): 7221-31.
[http://dx.doi.org/10.18632/oncotarget.3372] [PMID: 25749047]
[36]
Malakhov MP, Kim KI, Malakhova OA, Jacobs BS, Borden EC, Zhang DE. High-throughput immunoblotting. Ubiquitiin-like protein ISG15 modifies key regulators of signal transduction. J Biol Chem 2003; 278(19): 16608-13.
[http://dx.doi.org/10.1074/jbc.M208435200] [PMID: 12582176]
[37]
Basters A, Geurink PP, El Oualid F, et al. Molecular characterization of ubiquitin-specific protease 18 reveals substrate specificity for interferon-stimulated gene 15. FEBS J 2014; 281(7): 1918-28.
[http://dx.doi.org/10.1111/febs.12754] [PMID: 24533902]
[38]
González-Sanz R, Mata M, Bermejo-Martín J, et al. ISG15 is upregulated in respiratory syncytial virus infection and reduces virus growth through protein is gylation. J Virol 2016; 90(7): 3428-38.
[http://dx.doi.org/10.1128/JVI.02695-15] [PMID: 26763998]
[39]
Lenschow DJ, Lai C, Frias-Staheli N, et al. IFN-stimulated gene 15 functions as a critical antiviral molecule against influenza, herpes, and Sindbis viruses. Proc Natl Acad Sci USA 2007; 104(4): 1371-6.
[http://dx.doi.org/10.1073/pnas.0607038104] [PMID: 17227866]
[40]
Speer SD, Li Z, Buta S, et al. ISG15 deficiency and increased viral resistance in humans but not mice. Nat Commun 2016; 7: 11496.
[http://dx.doi.org/10.1038/ncomms11496] [PMID: 27193971]
[41]
Bogunovic D, Byun M, Durfee LA, et al. Mycobacterial disease and impaired IFN- immunity in humans with inherited ISG15 deficiency. Science 2012; 337: 1684-8.
[http://dx.doi.org/10.1126/science.1224026]
[42]
Freitas BT, Durie IA, Murray J, et al. Characterization and noncovalent inhibition of the deubiquitinase and deisgylase activity of SARS-CoV-2 papain-like protease. ACS Infect Dis 2020; 6(8): 2099-109.
[http://dx.doi.org/10.1021/acsinfecdis.0c00168] [PMID: 32428392]
[43]
Zhang X, Bogunovic D, Payelle-Brogard B, et al. Human intracellular ISG15 prevents interferon-/ over-amplification and auto-inflammation. Nature 2015; 517(7532): 89-93.
[http://dx.doi.org/10.1038/nature13801] [PMID: 25307056]
[44]
Vuillier F, Li Z, Commere PH, Dynesen LT, Pellegrini S. USP18 and ISG15 coordinately impact on SKP2 and cell cycle progression. Sci Rep 2019; 9(1): 4066.
[http://dx.doi.org/10.1038/s41598-019-39343-7] [PMID: 30858391]
[45]
Sulea T, Lindner HA, Purisima EO, Ménard R. Deubiquitination, a new function of the severe acute respiratory syndrome coronavirus papain-like protease? J Virol 2005; 79(7): 4550-1.
[http://dx.doi.org/10.1128/JVI.79.7.4550-4551.2005] [PMID: 15767458]
[46]
Lindner HA, Fotouhi-Ardakani N, Lytvyn V, Lachance P, Sulea T, Ménard R. The papain-like protease from the severe acute respiratory syndrome coronavirus is a deubiquitinating enzyme. J Virol 2005; 79(24): 15199-208.
[http://dx.doi.org/10.1128/JVI.79.24.15199-15208.2005] [PMID: 16306591]
[47]
Dang W, Xu L, Yin Y, et al. IRF-1, RIG-I and MDA5 display potent antiviral activities against norovirus coordinately induced by different types of interferons. Antiviral Res 2018; 155: 48-59.
[http://dx.doi.org/10.1016/j.antiviral.2018.05.004] [PMID: 29753657]
[48]
Onomoto K, Onoguchi K, Yoneyama M. Regulation of RIG-I-like receptor-mediated signaling: interaction between host and viral factors. Cell Mol Immunol 2021; 18(3): 539-55.
[http://dx.doi.org/10.1038/s41423-020-00602-7] [PMID: 33462384]
[49]
Jin Z, Du X, Xu Y, et al. Structure of Mpro from SARS-CoV-2 and discovery of its inhibitors. Nature 2020; 582(7811): 289-93.
[http://dx.doi.org/10.1038/s41586-020-2223-y] [PMID: 32272481]
[50]
Kanhed AM, Patel DV, Teli DM, Patel NR, Chhabria MT, Yadav MR. Identification of potential Mpro inhibitors for the treatment of COVID-19 by using systematic virtual screening approach. Mol Divers 2021; 25(1): 383-401.
[http://dx.doi.org/10.1007/s11030-020-10130-1] [PMID: 32737681]
[51]
Barretto N, Jukneliene D, Ratia K, Chen Z, Mesecar AD, Baker SC. The papain-like protease of severe acute respiratory syndrome coronavirus has deubiquitinating activity. J Virol 2005; 79(24): 15189-98.
[http://dx.doi.org/10.1128/JVI.79.24.15189-15198.2005] [PMID: 16306590]
[52]
Liu G, Lee JH, Parker ZM, et al. ISG15-dependent activation of the sensor MDA5 is antagonized by the SARS-CoV-2 papain-like protease to evade host innate immunity. Nat Microbiol 2021; 6(4): 467-78.
[http://dx.doi.org/10.1038/s41564-021-00884-1] [PMID: 33727702]
[53]
Chiang C, Liu G, Gack MU. Viral evasion of rig-i-like receptor-mediated immunity through dysregulation of ubiquitination and isgylation. Viruses 2021; 13(2): 182.
[http://dx.doi.org/10.3390/v13020182] [PMID: 33530371]
[54]
Stasiulewicz A, Maksymiuk AW, Nguyen ML. Beza B, Sulkowska JI. SARS-CoV-2 papain-like protease potential inhibitors in silico quantitative assessment. Int J Mol Sci 2021; 22(8): 3957.
[http://dx.doi.org/10.3390/ijms22083957] [PMID: 33921228]
[55]
Leite WC, Weiss KL, Phillips G, et al. Conformational dynamics in the interaction of SARS-CoV-2 papain-like protease with human interferon-stimulated gene 15 protein. J Phys Chem Lett 2021; 12(23): 5608-15.
[http://dx.doi.org/10.1021/acs.jpclett.1c00831] [PMID: 34110168]
[56]
Liu G, Lee J-H, Parker ZM, et al. ISG15-dependent activation of the RNA sensor MDA5 and its antagonism by the SARS-CoV-2 papain-like protease. BioRxiv 2020.
[http://dx.doi.org/10.1101/2020.10.26.356048]
[57]
Shin D, Mukherjee R, Grewe D, et al. Inhibition of papain-like protease PLpro blocks SARS-CoV-2 spread and promotes anti-viral immunity. Res Square 2020.
[http://dx.doi.org/10.21203/rs.3.rs-27134/v1]
[58]
Fung SY, Siu KL, Lin H, Yeung ML, Jin DY. SARS-CoV-2 main protease suppresses type I interferon production by preventing nuclear translocation of phosphorylated IRF3. Int J Biol Sci 2021; 17(6): 1547-54.
[http://dx.doi.org/10.7150/ijbs.59943] [PMID: 33907518]
[59]
Munnur D, Teo Q, Eggermont D, et al. Altered ISGylation drives aberrant macrophage-dependent immune responses during SARS-CoV-2 infection. Nat Immunol 2021; 22(11): 1416-27.
[http://dx.doi.org/10.1038/s41590-021-01035-8] [PMID: 34663977]
[60]
Ratia K, Pegan S, Takayama J, et al. A noncovalent class of papain-like protease/deubiquitinase inhibitors blocks SARS virus replication. Proc Natl Acad Sci USA 2008; 105(42): 16119-24.
[http://dx.doi.org/10.1073/pnas.0805240105] [PMID: 18852458]
[61]
Báez-Santos YM, Barraza SJ, Wilson MW, et al. X-ray structural and biological evaluation of a series of potent and highly selective inhibitors of human coronavirus papain-like proteases. J Med Chem 2014; 57(6): 2393-412.
[http://dx.doi.org/10.1021/jm401712t] [PMID: 24568342]
[62]
Báez-Santos YM, Mielech AM, Deng X, Baker S, Mesecar AD. Catalytic function and substrate specificity of the papain-like protease domain of nsp3 from the Middle East respiratory syndrome coronavirus. J Virol 2014; 88(21): 12511-27.
[http://dx.doi.org/10.1128/JVI.01294-14] [PMID: 25142582]
[63]
Shin D, Mukherjee R, Grewe D, et al. Papain-like protease regulates SARS-CoV-2 viral spread and innate immunity. Nature 2020; 587(7835): 657-62.
[http://dx.doi.org/10.1038/s41586-020-2601-5] [PMID: 32726803]
[64]
Anirudhan V, Lee H, Cheng H, Cooper L, Rong L. Targeting SARS-CoV-2 viral proteases as a therapeutic strategy to treat COVID-19. J Med Virol 2021; 93(5): 2722-34.
[http://dx.doi.org/10.1002/jmv.26814] [PMID: 33475167]
[65]
Rajpoot S, Alagumuthu M, Baig MS. Dual targeting of 3CLpro and PLpro of SARS-CoV-2: A novel structure-based design approach to treat COVID-19. Curr Res Struct Biol 2021; 3: 9-18.
[http://dx.doi.org/10.1016/j.crstbi.2020.12.001] [PMID: 33319212]
[66]
Pitsillou E, Liang J, Hung A, Karagiannis TC. Inhibition of interferon-stimulated gene 15 and lysine 48-linked ubiquitin binding to the SARS-CoV-2 papain-like protease by small molecules: In silico studies. Chem Phys Lett 2021; 771138468
[http://dx.doi.org/10.1016/j.cplett.2021.138468] [PMID: 33716308]
[67]
Clemente V, D’Arcy P, Bazzaro M. Deubiquitinating enzymes in coronaviruses and possible therapeutic opportunities for COVID-19. Int J Mol Sci 2020; 21(10)E3492
[http://dx.doi.org/10.3390/ijms21103492] [PMID: 32429099]
[68]
Klemm T, Ebert G, Calleja DJ, et al. Mechanism and inhibition of the papain-like protease, PLpro, of SARS-CoV-2. EMBO J 2020; 39(18)e106275
[http://dx.doi.org/10.15252/embj.2020106275] [PMID: 32845033]
[69]
Iglesias-Guimarais V, Ahrends T, de Vries E, Knobeloch K-P, Volkov A, Borst J. IFN-stimulated gene 15 is an alarmin that boosts the CTL Response via an innate, NK cell-dependent route. J Immunol 2020; 204(8): 2110-21.
[http://dx.doi.org/10.4049/jimmunol.1901410] [PMID: 32169846]
[70]
Villarreal DO, Wise MC, Siefert RJ, Yan J, Wood LM, Weiner DB. Ubiquitin-like molecule ISG15 acts as an immune adjuvant to enhance antigen-specific CD8 T-cell tumor immunity Mol Ther 2015; 23(10): 1653-62.
[http://dx.doi.org/10.1038/mt.2015.120] [PMID: 26122932]

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