ISGylation: A Key Host Cellular Defense Mechanism

[{“box”:0,”content”:”[if 992 equals=”Open Access”]n

n

n

n

Open Access

nn

n

n[/if 992]n

n

Year : July 20, 2024 at 11:26 am | [if 1553 equals=””] Volume : [else] Volume :[/if 1553] | [if 424 equals=”Regular Issue”]Issue[/if 424][if 424 equals=”Special Issue”]Special Issue[/if 424] [if 424 equals=”Conference”][/if 424] : | Page : –

n

n

n

n

n

n

By

n

[foreach 286]n

n

n

Shreya Vashishtha, Kinjal Srivastava, Vibha Gupta,

n

    n t

  • n

n

n[/foreach]

n

n[if 2099 not_equal=”Yes”]n

    [foreach 286] [if 1175 not_equal=””]n t

  1. Project Assistant, UG Student, Assistant Professor Department of Biotechnology, Jaypee Institute of Information Technology, Noida, Department of Biotechnology, Jaypee Institute of Information Technology, Noida, Department of Biotechnology, Jaypee Institute of Information Technology, Noida Uttar Pradesh, Uttar Pradesh, Uttar Pradesh India, India, India

    2. n[/if 1175][/foreach]

n[/if 2099][if 2099 equals=”Yes”][/if 2099]n

n

Abstract

nISGylation, a crucial process of the innate immune response, has garnered increasing attention for its involvement in host’s defense against pathogenic infections as well in cancer progression. The key player of ISGylation, ISG15, is stimulated by type I interferons (IFNs). ISG15 covalently binds with viral (influenza NS1A and nucleoproteins) and host (Nedd4, filamin B and CHMP5) target proteins and this interaction inhibits the viral replication process and release of viral particles respectively. The ISGylation process dynamically modifies the immune signalling pathways mediated by NFkB, JNK, and IRF-3, which are crucial for immune response. ISG15 has diverse roles beyond ISGylations, for instance the free extracellular ISG15 serves as immunostimulatory cytokine in response to type-I interferon expression and free intracellular ISG15 is involved in stabilization and destabilization of various cellular proteins such as Ubiquitin-specific protease 18 (USP18) and Cyclin D1. The reversal of ISGylation is known as deISGylation where USP18 an ISG15 specific protease plays a crucial role. USP18 is a potent inhibitor of interferon signaling thus inculpated in the suppression of innate immune response in host cell. The future studies focusing on ISGylation research encompass a deeper exploration of its molecular mechanisms, diagnostic utility, crosstalk with other immune responses, and potential therapeutic interventions. This review consolidates updated literature on state-of-art for ISGylation and its role in providing immunity to human host together with deISGylation process, and strategies to counter deISGylation. By advancing our comprehension on ISGylation we can more effectively harness ISGylation’s potential to strengthen immune function and provide novel therapies for infections and cancer.

n

n

n

Keywords: ISG15; Innate immunity; ISGylation; DeISGylation; USP18; pathogenies

n[if 424 equals=”Regular Issue”][This article belongs to Research & Reviews : A Journal of Life Sciences(rrjols)]

n

[/if 424][if 424 equals=”Special Issue”][This article belongs to Special Issue under section in Research & Reviews : A Journal of Life Sciences(rrjols)][/if 424][if 424 equals=”Conference”]This article belongs to Conference [/if 424]

n

n

n

How to cite this article: Shreya Vashishtha, Kinjal Srivastava, Vibha Gupta. ISGylation: A Key Host Cellular Defense Mechanism. Research & Reviews : A Journal of Life Sciences. July 20, 2024; ():-.

n

How to cite this URL: Shreya Vashishtha, Kinjal Srivastava, Vibha Gupta. ISGylation: A Key Host Cellular Defense Mechanism. Research & Reviews : A Journal of Life Sciences. July 20, 2024; ():-. Available from: https://journals.stmjournals.com/rrjols/article=July 20, 2024/view=0

nn[if 992 equals=”Open Access”] Full Text PDF Download[/if 992] n

n[if 992 not_equal=’Open Access’]
[/if 992]n

n

n

nn[if 379 not_equal=””]n

Browse Figures

n

n

[foreach 379]n

n[/foreach]n

n

n

n[/if 379]n

n

References

n[if 1104 equals=””]n

  1. Liu Y, Wang Y, Liu J, Kang R, Tang D. Interplay between MTOR and GPX4 signaling modulates autophagy-dependent ferroptotic cancer cell death. Cancer Gene Ther. 2021 Feb 27;28(1–2):55–63.
  2. Zhang X, Bogunovic D, Payelle-Brogard B, Francois-Newton V, Speer SD, Yuan C, et al. Human intracellular ISG15 prevents interferon-α/β over-amplification and auto-inflammation. Nature. 2015 Jan 1;517(7532):89–93.
  3. Lenschow DJ, Giannakopoulos N V., Gunn LJ, Johnston C, O’Guin AK, Schmidt RE, et al. Identification of Interferon-Stimulated Gene 15 as an Antiviral Molecule during Sindbis Virus Infection In Vivo. J Virol. 2005 Nov 15;79(22):13974–83.
  4. D’Cunha J, Knight E, Haas AL, Truitt RL, Borden EC. Immunoregulatory properties of ISG15, an interferon-induced cytokine. Proceedings of the National Academy of Sciences. 1996 Jan 9;93(1):211–5.
  5. Recht M, Borden EC, Knight E. A human 15-kDa IFN-induced protein induces the secretion of IFN-gamma. J Immunol. 1991 Oct 15;147(8):2617–23.
  6. Yuan W. Influenza B virus NS1 protein inhibits conjugation of the interferon (IFN)-induced ubiquitin-like ISG15 protein. EMBO J. 2001 Feb 1;20(3):362–71.
  7. Zou W, Zhang DE. The Interferon-inducible Ubiquitin-protein Isopeptide Ligase (E3) EFP Also Functions as an ISG15 E3 Ligase. Journal of Biological Chemistry. 2006 Feb;281(7):3989–94.
  8. Malakhov MP, Malakhova OA, Kim K Il, Ritchie KJ, Zhang DE. UBP43 (USP18) specifically removes ISG15 from conjugated proteins. J Biol Chem. 2002 Mar 22;277(12):9976–81.
  9. Malakhova OA, Kim KII, Luo JK, Zou W, Kumar KGS, Fuchs SY, et al. UBP43 is a novel regulator of interferon signaling independent of its ISG15 isopeptidase activity. EMBO J. 2006 Jun 7;25(11):2358–67.
  10. Haas AL, Ahrens P, Bright PM, Ankel H. Interferon induces a 15-kilodalton protein exhibiting marked homology to ubiquitin. J Biol Chem. 1987 Aug 15;262(23):11315–23.
  11. Loeb KR, Haas AL. The interferon-inducible 15-kDa ubiquitin homolog conjugates to intracellular proteins. Journal of Biological Chemistry. 1992 Apr;267(11):7806–13.
  12. Kang JA, Jeon YJ. Emerging Roles of USP18: From Biology to Pathophysiology. Int J Mol Sci. 2020 Sep 17;21(18):6825.
  13. Perng YC, Lenschow DJ. ISG15 in antiviral immunity and beyond. Nat Rev Microbiol. 2018 Jul 16;16(7):423–39.
  14. Kim K Il, Zhang DE. ISG15, not just another ubiquitin-like protein. Biochem Biophys Res Commun. 2003 Aug 1;307(3):431–4.
  15. Bogunovic D, Byun M, Durfee LA, Abhyankar A, Sanal O, Mansouri D, et al. Mycobacterial disease and impaired IFN-γ immunity in humans with inherited ISG15 deficiency. Science. 2012 Sep 28;337(6102):1684–8.
  16. de Groot REA, Ganji RS, Bernatik O, Lloyd-Lewis B, Seipel K, Šedová K, et al. Huwe1-mediated ubiquitylation of dishevelled defines a negative feedback loop in the Wnt signaling pathway. Sci Signal. 2014 Mar 18;7(317):ra26.
  17. Malakhova OA, Zhang DE. ISG15 inhibits Nedd4 ubiquitin E3 activity and enhances the innate antiviral response. J Biol Chem. 2008 Apr 4;283(14):8783–7.
  18. Cheng A, Wong SM, Yuan YA. Structural basis for dsRNA recognition by NS1 protein of influenza A virus. Cell Res. 2009 Feb 23;19(2):187–95.
  19. Giannakopoulos N V., Arutyunova E, Lai C, Lenschow DJ, Haas AL, Virgin HW. ISG15 Arg151 and the ISG15-Conjugating Enzyme UbE1L Are Important for Innate Immune Control of Sindbis Virus. J Virol. 2009 Feb 15;83(4):1602–10.
  20. Li L, Wang D, Jiang Y, Sun J, Zhang S, Chen Y, et al. Crystal structure of human ISG15 protein in complex with influenza B virus NS1B. Journal of Biological Chemistry [Internet]. 2011 Sep 2 [cited 2024 Jan 16];286(35):30258–62. Available from: http://www.jbc.org/article/S0021925820723069/fulltext
  21. Kang JA, Kim YJ, Jeon YJ. The diverse repertoire of ISG15: more intricate than initially thought. Experimental & Molecular Medicine 2022 54:11 [Internet]. 2022 Nov 1 [cited 2024 Jan 22];54(11):1779–92. Available from: https://www.nature.com/articles/s12276-022-00872-3
  22. Potter JL, Narasimhan J, Mende-Mueller L, Haas AL. Precursor processing of pro-ISG15/UCRP, an interferon-β-induced ubiquitin-like protein. Journal of Biological Chemistry [Internet]. 1999 Aug 27 [cited 2024 Jan 22];274(35):25061–8. Available from: http://www.jbc.org/article/S0021925819554515/fulltext
  23. Narasimhan J, Wang M, Fu Z, Klein JM, Haas AL, Kim JJP. Crystal Structure of the Interferon-induced Ubiquitin-like Protein ISG15. Journal of Biological Chemistry. 2005 Jul;280(29):27356–65.
  24. Okumura A, Pitha PM, Harty RN. ISG15 inhibits Ebola VP40 VLP budding in an L-domain-dependent manner by blocking Nedd4 ligase activity. Proceedings of the National Academy of Sciences. 2008 Mar 11;105(10):3974–9.
  25. D’Cunha J, Ramanujam S, Wagner RJ, Witt PL, Knight E, Borden EC. In vitro and in vivo secretion of human ISG15, an IFN-induced immunomodulatory cytokine. J Immunol. 1996 Nov 1;157(9):4100–8.
  26. Sun L, Wang X, Zhou Y, Zhou RH, Ho WZ, Li JL. Exosomes contribute to the transmission of anti-HIV activity from TLR3-activated brain microvascular endothelial cells to macrophages. Antiviral Res. 2016 Oct;134:167–71.
  27. Care MA, Stephenson SJ, Barnes NA, Fan I, Zougman A, El-Sherbiny YM, et al. Network Analysis Identifies Proinflammatory Plasma Cell Polarization for Secretion of ISG15 in Human Autoimmunity. The Journal of Immunology. 2016 Aug 15;197(4):1447–59.
  28. Munnur D, Teo Q, Eggermont D, Lee HHY, Thery F, Ho J, et al. Altered ISGylation drives aberrant macrophage-dependent immune responses during SARS-CoV-2 infection. Nat Immunol. 2021 Nov 18;22(11):1416–27.
  29. Mathieu NA, Paparisto E, Barr SD, Spratt DE. HERC5 and the ISGylation Pathway: Critical Modulators of the Antiviral Immune Response. Viruses. 2021 Jun 9;13(6):1102.
  30. Cao X. ISG15 secretion exacerbates inflammation in SARS-CoV-2 infection. Nat Immunol. 2021 Nov 20;22(11):1360–2.
  31. Okumura A, Lu G, Pitha-Rowe I, Pitha PM. Innate antiviral response targets HIV-1 release by the induction of ubiquitin-like protein ISG15. Proc Natl Acad Sci U S A [Internet]. 2006 Jan 31 [cited 2024 Jan 22];103(5):1440–5. Available from: https://www.pnas.org/doi/abs/10.1073/pnas.0510518103
  32. Boutell C, Sadis S, Everett RD. Herpes Simplex Virus Type 1 Immediate-Early Protein ICP0 and Its Isolated RING Finger Domain Act as Ubiquitin E3 Ligases In Vitro. J Virol [Internet]. 2002 Jan 15 [cited 2024 Jan 22];76(2):841–50. Available from: https://journals.asm.org/doi/10.1128/jvi.76.2.841-850.2002
  33. Sheehy AM, Gaddis NC, Choi JD, Malim MH. Isolation of a human gene that inhibits HIV-1 infection and is suppressed by the viral Vif protein. Nature. 2002 Aug 14;418(6898):646–50.
  34. Zhang H, Yang B, Pomerantz RJ, Zhang C, Arunachalam SC, Gao L. The cytidine deaminase CEM15 induces hypermutation in newly synthesized HIV-1 DNA. Nature. 2003 Jul 28;424(6944):94–8.
  35. Vogt VM. Ubiquitin in retrovirus assembly: Actor or bystander? Proceedings of the National Academy of Sciences. 2000 Nov 21;97(24):12945–7.
  36. Freed EO. HIV-1 Gag Proteins: Diverse Functions in the Virus Life Cycle. Virology. 1998 Nov;251(1):1–15.
  37. Katzmann DJ, Babst M, Emr SD. Ubiquitin-Dependent Sorting into the Multivesicular Body Pathway Requires the Function of a Conserved Endosomal Protein Sorting Complex, ESCRT-I. Cell. 2001 Jul;106(2):145–55.
  38. Levy JA, Scott I, Mackewicz C. Protection from HIV/AIDS: the importance of innate immunity. Clinical Immunology. 2003 Sep;108(3):167–74.
  39. Göttlinger HG, Dorfman T, Sodroski JG, Haseltine WA. Effect of mutations affecting the p6 gag protein on human immunodeficiency virus particle release. Proceedings of the National Academy of Sciences. 1991 Apr 15;88(8):3195–9.
  40. Gendelman HE, Baca LM, Turpin J, Kalter DC, Hansen B, Orenstein JM, et al. Regulation of HIV replication in infected monocytes by IFN-alpha. Mechanisms for viral restriction. The Journal of Immunology. 1990 Oct 15;145(8):2669–76.
  41. KÜNZI MS, PITHA PM. Role of Interferon-Stimulated Gene ISG-15 in the Interferon-ω-Mediated Inhibition of Human Immunodeficiency Virus Replication. Journal of Interferon & Cytokine Research. 1996 Nov;16(11):919–27.
  42. Strack B, Calistri A, Göttlinger HG. Late Assembly Domain Function Can Exhibit Context Dependence and Involves Ubiquitin Residues Implicated in Endocytosis. J Virol. 2002 Jun;76(11):5472–9.
  43. Zhao C, Hsiang TY, Kuo RL, Krug RM. ISG15 conjugation system targets the viral NS1 protein in influenza A virus–infected cells. Proceedings of the National Academy of Sciences. 2010 Feb 2;107(5):2253–8.
  44. Krug RM, Yuan W, Noah DL, Latham AG. Intracellular warfare between human influenza viruses and human cells: the roles of the viral NS1 protein. Virology. 2003 May;309(2):181–9.
  45. Zhao C, Hsiang TY, Kuo RL, Krug RM. ISG15 conjugation system targets the viral NS1 protein in influenza A virus–infected cells. Proceedings of the National Academy of Sciences. 2010 Feb 2;107(5):2253–8.
  46. Cheng A, Wong SM, Yuan YA. Structural basis for dsRNA recognition by NS1 protein of influenza A virus. Cell Res. 2009 Feb 23;19(2):187–95.
  47. Hatada E, Fukuda R. Binding of influenza A virus NS1 protein to dsRNA in vitro. Journal of General Virology. 1992 Dec 1;73(12):3325–9.
  48. Melén K, Kinnunen L, Fagerlund R, Ikonen N, Twu KY, Krug RM, et al. Nuclear and Nucleolar Targeting of Influenza A Virus NS1 Protein: Striking Differences between Different Virus Subtypes. J Virol. 2007 Jun;81(11):5995–6006.
  49. Radoshevich L, Impens F, Ribet D, Quereda JJ, Nam Tham T, Nahori MA, et al. ISG15 counteracts Listeria monocytogenes infection. Elife. 2015 Aug 11;4.
  50. Dalrymple SA, Lucian LA, Slattery R, McNeil T, Aud DM, Fuchino S, et al. Interleukin-6-deficient mice are highly susceptible to Listeria monocytogenes infection: correlation with inefficient neutrophilia. Infect Immun. 1995 Jun;63(6):2262–8.
  51. Baggiolini M, Clark-Lewis I. Interleukin‐8, a chemotactic and inflammatory cytokine. FEBS Lett. 1992 Jul 27;307(1):97–101.
  52. Kimmey JM, Campbell JA, Weiss LA, Monte KJ, Lenschow DJ, Stallings CL. The impact of ISGylation during Mycobacterium tuberculosis infection in mice. Microbes Infect. 2017 Apr;19(4–5):249–58.
  53. Fan JB, Zhang DE. ISG15 regulates IFN-γ immunity in human mycobacterial disease. Cell Res. 2013 Feb 11;23(2):173–5.
  54. Jouanguy E, Lamhamedi-Cherradi S, Lammas D, Dorman SE, Fondanèche MC, Dupuis S, et al. A human IFNGR1 small deletion hotspot associated with dominant susceptibility to mycobacterial infection. Nat Genet. 1999 Apr;21(4):370–8.
  55. Gao N, Me R, Dai C, Yu F shin X. ISG15 Acts as a Mediator of Innate Immune Response to Pseudomonas aeruginosa Infection in C57BL/6J Mouse Corneas. Investigative Opthalmology & Visual Science. 2020 May 16;61(5):26.
  56. Kumar A, Yu FS. Toll-Like Receptors and Corneal Innate Immunity. Curr Mol Med. 2006 May 1;6(3):327–37.
  57. Desai SD, Haas AL, Wood LM, Tsai YC, Pestka S, Rubin EH, et al. Elevated expression of ISG15 in tumor cells interferes with the ubiquitin/26S proteasome pathway. Cancer Res. 2006 Jan 15;66(2):921–8.
  58. Mirzalieva O, Juncker M, Schwartzenburg J, Desai S. ISG15 and ISGylation in Human Diseases. Vol. 11, Cells. MDPI; 2022.
  59. Hermann MR, Jakobson M, Colo GP, Rognoni E, Jakobson M, Kupatt C, et al. Integrins synergise to induce expression of the MRTF-A-SRF target gene ISG15 for promoting cancer cell invasion. J Cell Sci. 2016 Apr 1;129(7):1391–403.
  60. Burks J, Reed RE, Desai SD. Free ISG15 triggers an antitumor immune response against breast cancer: a new perspective. Oncotarget. 2015 Mar 30;6(9):7221–31.
  61. Nakka VP, Mohammed AQ. A Critical Role for ISGylation, Ubiquitination and, SUMOylation in Brain Damage: Implications for Neuroprotection. Neurochem Res. 2020 Sep 4;45(9):1975–85.
  62. Guo C, Henley JM. Wrestling with stress: Roles of protein SUMOylation and deSUMOylation in cell stress response. IUBMB Life. 2014 Feb 27;66(2):71–7.
  63. Zhang M, Li J, Yan H, Huang J, Wang F, Liu T, et al. ISGylation in Innate Antiviral Immunity and Pathogen Defense Responses: A Review. Vol. 9, Frontiers in Cell and Developmental Biology. Frontiers Media S.A.; 2021.
  64. Kang D chul, Gopalkrishnan R V, Wu Q, Jankowsky E, Pyle AM, Fisher PB. mda-5: An interferon-inducible putative RNA helicase with double-stranded RNA-dependent ATPase activity and melanoma growth-suppressive properties. Proc Natl Acad Sci U S A. 2002 Jan 22;99(2):637–42.
  65. Liu LQ, Ilaria R, Kingsley PD, Iwama A, van Etten RA, Palis J, et al. A Novel Ubiquitin-Specific Protease, UBP43, Cloned from Leukemia Fusion Protein AML1-ETO-Expressing Mice, Functions in Hematopoietic Cell Differentiation. Mol Cell Biol. 1999 Apr 1;19(4):3029–38.
  66. Kang D chul, Jiang H, Wu Q, Pestka S, Fisher PB. Cloning and characterization of human ubiquitin-processing protease-43 from terminally differentiated human melanoma cells using a rapid subtraction hybridization protocol RaSH. Gene. 2001 Apr;267(2):233–42.
  67. Zhang X, Shin J, Molitor TW, Schook LB, Rutherford MS. Molecular Responses of Macrophages to Porcine Reproductive and Respiratory Syndrome Virus Infection. Virology. 1999 Sep;262(1):152–62.
  68. Dziamałek-Macioszczyk P, Haraźna J, Stompór T. Versatility of USP18 in physiology and pathophysiology. Acta Biochim Pol. 2019 Nov 20;
  69. Jiménez Fernández D, Hess S, Knobeloch KP. Strategies to Target ISG15 and USP18 Toward Therapeutic Applications. Front Chem. 2020 Jan 21;7.
  70. Narasimhan J, Potter JL, Haas AL. Conjugation of the 15-kDa Interferon-induced Ubiquitin Homolog Is Distinct from That of Ubiquitin. Journal of Biological Chemistry. 1996 Jan;271(1):324–30.
  71. Honke N, Shaabani N, Zhang DE, Hardt C, Lang KS. Multiple functions of USP18. Cell Death Dis. 2016 Nov 3;7(11):e2444–e2444.
  72. Hochstrasser M. UBIQUITIN-DEPENDENT PROTEIN DEGRADATION. Annu Rev Genet. 1996 Dec;30(1):405–39.
  73. Malakhov MP, Malakhova OA, Kim K Il, Ritchie KJ, Zhang DE. UBP43 (USP18) Specifically Removes ISG15 from Conjugated Proteins. Journal of Biological Chemistry. 2002 Mar;277(12):9976–81.
  74. Zhang X, Bogunovic D, Payelle-Brogard B, Francois-Newton V, Speer SD, Yuan C, et al. Human intracellular ISG15 prevents interferon-α/β over-amplification and auto-inflammation. Nature. 2015 Jan 1;517(7532):89–93.
  75. Liu X, Li H, Zhong B, Blonska M, Gorjestani S, Yan M, et al. USP18 inhibits NF-κB and NFAT activation during Th17 differentiation by deubiquitinating the TAK1–TAB1 complex. Journal of Experimental Medicine. 2013 Jul 29;210(8):1575–90.
  76. Frias-Staheli N, Giannakopoulos N V., Kikkert M, Taylor SL, Bridgen A, Paragas J, et al. Ovarian Tumor Domain-Containing Viral Proteases Evade Ubiquitin- and ISG15-Dependent Innate Immune Responses. Cell Host Microbe. 2007 Dec;2(6):404–16.
  77. Mielech AM, Kilianski A, Baez-Santos YM, Mesecar AD, Baker SC. MERS-CoV papain-like protease has deISGylating and deubiquitinating activities. Virology. 2014 Feb;450–451:64–70.
  78. 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 Dec 15;79(24):15199–208.
  79. Bianco C, Mohr I. Restriction of Human Cytomegalovirus Replication by ISG15, a Host Effector Regulated by cGAS-STING Double-Stranded-DNA Sensing. J Virol. 2017 May;91(9).
  80. Kim YJ, Kim ET, Kim YE, Lee MK, Kwon KM, Kim K Il, et al. Consecutive Inhibition of ISG15 Expression and ISGylation by Cytomegalovirus Regulators. PLoS Pathog. 2016 Aug 26;12(8):e1005850.

nn[/if 1104][if 1104 not_equal=””]n

    [foreach 1102]n t

  1. [if 1106 equals=””], [/if 1106][if 1106 not_equal=””],[/if 1106]

    2. n[/foreach]

n[/if 1104]

nn

nn[if 1114 equals=”Yes”]n

n[/if 1114]

n

n

[if 424 not_equal=””][else]Ahead of Print[/if 424] Subscription Review Article

n

n

n

n

n

Research & Reviews : A Journal of Life Sciences

n

[if 344 not_equal=””]ISSN: 2249-8656[/if 344]

n

n

n

n

n

[if 2146 equals=”Yes”][/if 2146][if 2146 not_equal=”Yes”][/if 2146]n

n

n

n

n

n

n

n

n

n

n

n

n

n

n

n

n

n

n

n

n[if 1748 not_equal=””]

[else]

[/if 1748]n

n

n

Volume
[if 424 equals=”Regular Issue”]Issue[/if 424][if 424 equals=”Special Issue”]Special Issue[/if 424] [if 424 equals=”Conference”][/if 424]
Received June 13, 2024
Accepted June 29, 2024
Published July 20, 2024

n

n

Views: 5

n

n

n

n nfunction myFunction2() {nvar x = document.getElementById(“browsefigure”);nif (x.style.display === “block”) {nx.style.display = “none”;n}nelse { x.style.display = “Block”; }n}ndocument.querySelector(“.prevBtn”).addEventListener(“click”, () => {nchangeSlides(-1);n});ndocument.querySelector(“.nextBtn”).addEventListener(“click”, () => {nchangeSlides(1);n});nvar slideIndex = 1;nshowSlides(slideIndex);nfunction changeSlides(n) {nshowSlides((slideIndex += n));n}nfunction currentSlide(n) {nshowSlides((slideIndex = n));n}nfunction showSlides(n) {nvar i;nvar slides = document.getElementsByClassName(“Slide”);nvar dots = document.getElementsByClassName(“Navdot”);nif (n > slides.length) { slideIndex = 1; }nif (n (item.style.display = “none”));nArray.from(dots).forEach(nitem => (item.className = item.className.replace(” selected”, “”))n);nslides[slideIndex – 1].style.display = “block”;ndots[slideIndex – 1].className += ” selected”;n}n”}]