{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T19:51:44Z","timestamp":1790797904553,"version":"4.1.0"},"reference-count":81,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2026,2,19]],"date-time":"2026-02-19T00:00:00Z","timestamp":1771459200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Consejo Nacional de Humanidades, Ciencia y Tecnolog\u00eda","award":["CF-2023-I-1597"],"award-info":[{"award-number":["CF-2023-I-1597"]}]},{"name":"Consejo Nacional de Humanidades, Ciencia y Tecnolog\u00eda","award":["961575"],"award-info":[{"award-number":["961575"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Human papillomavirus type 16 (HPV16) persistence relies on early viral mechanisms that synchronize oncogenic signaling with immune evasion, with the E5 oncoprotein serving as a central regulator of the viral cycle and the initiation of cell transformation. This review integrates current evidence on how E5 reconfigures host cell dynamics: first, by hijacking signaling pathways such as EGFR, MAPK\/ERK, and PI3K\/AKT to drive keratinocyte proliferation and survival; and second, by organizing a multi-step immune evasion strategy. We detail how E5 suppresses innate antiviral responses, specifically by repressing IFN-\u03ba and IFN-\u03b2 via interference with IRF1, TGF-\u03b2\/SMAD, STING, and MAVS signaling. Simultaneously, E5 interferes with the adaptive immunity by disrupting MHC-I trafficking and impairing MHC-II maturation. Furthermore, preclinical studies utilizing various vaccine platforms targeting HPV16 E5 have demonstrated the capacity to reduce tumor burden and significantly increase survival rates. By integrating these molecular and immunological checkpoints, we highlight the role of E5 in sustaining viral persistence and underscore its potential as a high-value target for next-generation immunotherapeutic and vaccine-based strategies.<\/jats:p>","DOI":"10.3390\/ijms27041985","type":"journal-article","created":{"date-parts":[[2026,2,19]],"date-time":"2026-02-19T09:55:31Z","timestamp":1771494931000},"page":"1985","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Role of E5 from HPV16 in the Evasion of the Immune Response"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5396-4407","authenticated-orcid":false,"given":"Aislinn C.","family":"P\u00e9rez-Morales","sequence":"first","affiliation":[{"name":"Centro de Investigaci\u00f3n Sobre Enfermedades Infecciosas, Instituto Nacional de Salud P\u00fablica, Cuernavaca 62100, Mexico"},{"name":"Centro de Investigaci\u00f3n en Din\u00e1mica Celular, Universidad Aut\u00f3noma del Estado de Morelos, Cuernavaca 62210, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minerva","family":"Maldonado-Gama","sequence":"additional","affiliation":[{"name":"Centro de Investigaci\u00f3n Sobre Enfermedades Infecciosas, Instituto Nacional de Salud P\u00fablica, Cuernavaca 62100, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marisela","family":"M\u00e9ndez-Armenta","sequence":"additional","affiliation":[{"name":"Departamento de Neuroqu\u00edmica, Instituto Nacional de Neurolog\u00eda y Neurocirug\u00eda, \u201cManuel Velasco Su\u00e1rez\u201d, Ciudad de M\u00e9xico 14269, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fernando","family":"Esquivel-Guadarrama","sequence":"additional","affiliation":[{"name":"Facultad de Medicina, Universidad Aut\u00f3noma del Estado de Morelos, Cuernavaca 62350, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lourdes","family":"Gutierrez-Xicotencatl","sequence":"additional","affiliation":[{"name":"Centro de Investigaci\u00f3n Sobre Enfermedades Infecciosas, Instituto Nacional de Salud P\u00fablica, Cuernavaca 62100, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,2,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/j.mrrev.2016.07.002","article-title":"Human Papillomavirus Molecular Biology","volume":"772","author":"Harden","year":"2017","journal-title":"Mutat. Res. Rev. Mutat. Res."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1016\/j.coviro.2016.08.011","article-title":"Human Papillomavirus Infection and Induction of Neoplasia: A Matter of Fitness","volume":"20","author":"Kranjec","year":"2016","journal-title":"Curr. Opin. Virol."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Schichl, K., and Doorbar, J. (2025). Regulation and Deregulation of Viral Gene Expression During High-Risk HPV Infection. Viruses, 17.","DOI":"10.3390\/v17070937"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Vallejo-Ruiz, V., Guti\u00e9rrez-Xicotencatl, L., Medina-Contreras, O., and Lizano, M. (2024). Molecular Aspects of Cervical Cancer: A Pathogenesis Update. Front. Oncol., 14.","DOI":"10.3389\/fonc.2024.1356581"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1016\/j.jab.2017.05.003","article-title":"The Role of Keratinocytes in Inflammation","volume":"15","year":"2017","journal-title":"J. Appl. Biomed."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1128\/JVI.01582-19","article-title":"Human Papillomavirus 16 E5 Inhibits Interferon Signaling and Supports Episomal Viral Maintenance","volume":"94","author":"Scott","year":"2020","journal-title":"J. Virol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"109716","DOI":"10.1016\/j.abb.2023.109716","article-title":"Advances in Molecular Mechanism of HPV16 E5 Oncoprotein Carcinogenesis","volume":"745","author":"Chen","year":"2023","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1016\/j.virol.2013.05.006","article-title":"The E5 Proteins","volume":"445","author":"DiMaio","year":"2013","journal-title":"Virology"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"103675","DOI":"10.1016\/j.critrevonc.2022.103675","article-title":"Mechanistic Role of HPV-Associated Early Proteins in Cervical Cancer: Molecular Pathways and Targeted Therapeutic Strategies","volume":"174","author":"Bhattacharjee","year":"2022","journal-title":"Crit. Rev. Oncol. Hematol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"2924","DOI":"10.1158\/0008-5472.CAN-09-3436","article-title":"A Role for HPV16 E5 in Cervical Carcinogenesis","volume":"70","author":"Maufort","year":"2010","journal-title":"Cancer Res."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Gargan, S., and Stevenson, N.J. (2021). Unravelling the Immunomodulatory Effects of Viral Ion Channels, towards the Treatment of Disease. Viruses, 13.","DOI":"10.3390\/v13112165"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1016\/j.canlet.2019.05.025","article-title":"AKT and ERK Dual Inhibitors: The Way Forward?","volume":"459","author":"Cao","year":"2019","journal-title":"Cancer Lett."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Skelin, J., Sabol, I., and Tomai\u0107, V. (2022). Do or Die: HPV E5, E6 and E7 in Cell Death Evasion. Pathogens, 11.","DOI":"10.3390\/pathogens11091027"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"3","DOI":"10.3892\/etm.2013.1374","article-title":"Human Papillomavirus Oncoproteins and Apoptosis (Review)","volume":"7","author":"Jiang","year":"2014","journal-title":"Exp. Ther. Med."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1541","DOI":"10.3892\/ijo.2017.4124","article-title":"Functional Diversity of MiR-146a-5p and TRAF6 in Normal and Oral Cancer Cells","volume":"51","author":"Min","year":"2017","journal-title":"Int. J. Oncol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"12481","DOI":"10.1073\/pnas.0605298103","article-title":"NF-KappaB-Dependent Induction of MicroRNA MiR-146, an Inhibitor Targeted to Signaling Proteins of Innate Immune Responses","volume":"103","author":"Taganov","year":"2006","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1016\/j.virol.2010.07.044","article-title":"HPV-16 E5 down-Regulates Expression of Surface HLA Class I and Reduces Recognition by CD8 T Cells","volume":"407","author":"Campo","year":"2010","journal-title":"Virology"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"27","DOI":"10.2217\/fvl.14.99","article-title":"Human Papillomavirus E5 Oncoprotein: Function and Potential Target for Antiviral Therapeutics","volume":"10","author":"Prescott","year":"2015","journal-title":"Future Virol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1071","DOI":"10.1038\/sj.onc.1210725","article-title":"HPV-16 E5 Oncoprotein Upregulates Lipid Raft Components Caveolin-1 and Ganglioside GM1 at the Plasma Membrane of Cervical Cells","volume":"27","author":"Suprynowicz","year":"2008","journal-title":"Oncogene"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"11614","DOI":"10.1128\/JVI.01053-10","article-title":"CD1d, a Sentinel Molecule Bridging Innate and Adaptive Immunity, Is Downregulated by the Human Papillomavirus (HPV) E5 Protein: A Possible Mechanism for Immune Evasion by HPV","volume":"84","author":"Miura","year":"2010","journal-title":"J. Virol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1186\/s43556-025-00381-5","article-title":"Interferon Signaling Pathways in Health and Disease","volume":"6","author":"Wen","year":"2025","journal-title":"Mol. Biomed."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"20047","DOI":"10.1074\/jbc.R700004200","article-title":"The Interferons: 50 Years after Their Discovery, There Is Much More to Learn","volume":"282","author":"Pestka","year":"2007","journal-title":"J. Biol. Chem."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Xu, B., Musai, J., Tan, Y.S., Hile, G.A., Swindell, W.R., Klein, B., Qin, J.T., Sarkar, M.K., Gudjonsson, J.E., and Kahlenberg, J.M. (2024). A Critical Role for IFN-\u03b2 Signaling for IFN-\u03ba Induction in Keratinocytes. Front. Lupus, 2.","DOI":"10.3389\/flupu.2024.1359714"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Mazewski, C., Perez, R.E., Fish, E.N., and Platanias, L.C. (2020). Type I Interferon (IFN)-Regulated Activation of Canonical and Non-Canonical Signaling Pathways. Front. Immunol., 11.","DOI":"10.3389\/fimmu.2020.606456"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"47777","DOI":"10.18632\/oncotarget.10013","article-title":"Epidermal Growth Factor Receptor Inhibitors Trigger a Type I Interferon Response in Human Skin","volume":"7","author":"Lulli","year":"2016","journal-title":"Oncotarget"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Dai, J., Zhou, P., Li, S., and Qiu, H.-J. (2022). New Insights into the Crosstalk among the Interferon and Inflammatory Signaling Pathways in Response to Viral Infections: Defense or Homeostasis. Viruses, 14.","DOI":"10.3390\/v14122798"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Maik-Rachline, G., Hacohen-Lev-Ran, A., and Seger, R. (2019). Nuclear ERK: Mechanism of Translocation, Substrates, and Role in Cancer. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20051194"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1186\/s13046-017-0541-1","article-title":"HrHPV E5 Oncoprotein: Immune Evasion and Related Immunotherapies","volume":"36","author":"Barros","year":"2017","journal-title":"J. Exp. Clin. Cancer Res."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"112508","DOI":"10.1016\/j.celrep.2023.112508","article-title":"Human Papillomavirus E5 Suppresses Immunity via Inhibition of the Immunoproteasome and STING Pathway","volume":"42","author":"Miyauchi","year":"2023","journal-title":"Cell Rep."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"282","DOI":"10.1038\/s41392-024-01980-4","article-title":"The Multiple Roles of Interferon Regulatory Factor Family in Health and Disease","volume":"9","author":"Wang","year":"2024","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"534","DOI":"10.1038\/s41568-025-00819-6","article-title":"Revisiting the TGF\u03b2 Paradox: Insights from HPV-Driven Cancer and the DNA Damage Response","volume":"25","author":"Yom","year":"2025","journal-title":"Nat. Rev. Cancer"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1142","DOI":"10.1038\/ni.3558","article-title":"Regulation and Function of the CGAS-STING Pathway of Cytosolic DNA Sensing","volume":"17","author":"Chen","year":"2016","journal-title":"Nat. Immunol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/j.coi.2020.04.002","article-title":"Conserved Strategies for Pathogen Evasion of CGAS\u2013STING Immunity","volume":"66","author":"Eaglesham","year":"2020","journal-title":"Curr. Opin. Immunol."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Hussain, B., Xie, Y., Jabeen, U., Lu, D., Yang, B., Wu, C., and Shang, G. (2022). Activation of STING Based on Its Structural Features. Front. Immunol., 13.","DOI":"10.3389\/fimmu.2022.808607"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1355","DOI":"10.1016\/j.celrep.2013.05.009","article-title":"The Innate Immune DNA Sensor CGAS Produces a Noncanonical Cyclic Dinucleotide That Activates Human STING","volume":"3","author":"Diner","year":"2013","journal-title":"Cell Rep."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Hu, T., Pan, M., Yin, Y., Wang, C., Cui, Y., and Wang, Q. (2021). The Regulatory Network of Cyclic GMP-AMP Synthase-Stimulator of Interferon Genes Pathway in Viral Evasion. Front. Microbiol., 12.","DOI":"10.3389\/fmicb.2021.790714"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1016\/j.it.2023.04.002","article-title":"The RNA Polymerase III-RIG-I Axis in Antiviral Immunity and Inflammation","volume":"44","author":"Naesens","year":"2023","journal-title":"Trends Immunol."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Sun, L., Chen, M., and Wang, X. (2025). RNA Polymerase III-Transcribed RNAs in Health and Disease: Mechanisms, Dysfunction, and Future Directions. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms26125852"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"166","DOI":"10.4161\/viru.2.2.15481","article-title":"Differential Recognition of Viral RNA by RIG-I","volume":"2","author":"Baum","year":"2011","journal-title":"Virulence"},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Li, P., and Chang, M. (2021). Roles of PRR-Mediated Signaling Pathways in the Regulation of Oxidative Stress and Inflammatory Diseases. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22147688"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"26811","DOI":"10.1074\/jbc.M115.666578","article-title":"Structural Insights into Mitochondrial Antiviral Signaling Protein (MAVS)-Tumor Necrosis Factor Receptor-Associated Factor 6 (TRAF6) Signaling","volume":"290","author":"Shi","year":"2015","journal-title":"J. Biol. Chem."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"104610","DOI":"10.1016\/j.critrevonc.2024.104610","article-title":"MAVS: The next STING in Cancers and Other Diseases","volume":"207","author":"Wang","year":"2025","journal-title":"Crit. Rev. Oncol. Hematol."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Shi, J.-H., and Sun, S.-C. (2018). Tumor Necrosis Factor Receptor-Associated Factor Regulation of Nuclear Factor \u039aB and Mitogen-Activated Protein Kinase Pathways. Front. Immunol., 9.","DOI":"10.3389\/fimmu.2018.01849"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"17023","DOI":"10.1038\/sigtrans.2017.23","article-title":"NF-\u039aB Signaling in Inflammation","volume":"2","author":"Liu","year":"2017","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1038\/s41392-024-01757-9","article-title":"NF-\u039aB in Biology and Targeted Therapy: New Insights and Translational Implications","volume":"9","author":"Guo","year":"2024","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"5070","DOI":"10.1128\/JVI.02114-10","article-title":"Human Papillomavirus Type 16 E5 Protein Induces Expression of Beta Interferon through Interferon Regulatory Factor 1 in Human Keratinocytes","volume":"85","author":"Muto","year":"2011","journal-title":"J. Virol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"753","DOI":"10.1093\/carcin\/bgp066","article-title":"Involvement of NF-KappaB and AP-1 in COX-2 Upregulation by Human Papillomavirus 16 E5 Oncoprotein","volume":"30","author":"Kim","year":"2009","journal-title":"Carcinogenesis"},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Gardella, B., Pasquali, M.F., and Dominoni, M. (2022). Human Papillomavirus Cervical Infection: Many Ways to a Single Destination. Vaccines, 11.","DOI":"10.3390\/vaccines11010022"},{"key":"ref_49","unstructured":"Becar, M., and Kasi, A. (2022). Physiology, MHC Class I, StatPearls Publishing."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1146\/annurev.cellbio.24.110707.175347","article-title":"Regulation of MHC Class I Assembly and Peptide Binding","volume":"24","author":"Peaper","year":"2008","journal-title":"Annu. Rev. Cell Dev. Biol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1038\/nri3818","article-title":"The Ins and Outs of MHC Class II-Mediated Antigen Processing and Presentation","volume":"15","author":"Roche","year":"2015","journal-title":"Nat. Rev. Immunol."},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Fortin, J.-S., Cloutier, M., and Thibodeau, J. (2013). Exposing the Specific Roles of the Invariant Chain Isoforms in Shaping the MHC Class II Peptidome. Front. Immunol., 4.","DOI":"10.3389\/fimmu.2013.00443"},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Ishina, I.A., Zakharova, M.Y., Kurbatskaia, I.N., Mamedov, A.E., Belogurov, A.A., and Gabibov, A.G. (2023). MHC Class II Presentation in Autoimmunity. Cells, 12.","DOI":"10.3390\/cells12020314"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"2485","DOI":"10.3390\/v7052485","article-title":"High-Risk Human Papillomavirus Targets Crossroads in Immune Signaling","volume":"7","author":"Tummers","year":"2015","journal-title":"Viruses"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1038\/nature24627","article-title":"Structure of the Human MHC-I Peptide-Loading Complex","volume":"551","author":"Blees","year":"2017","journal-title":"Nature"},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Margulies, D.H., Jiang, J., Ahmad, J., Boyd, L.F., and Natarajan, K. (2023). Chaperone Function in Antigen Presentation by MHC Class I Molecules-Tapasin in the PLC and TAPBPR Beyond. Front. Immunol., 14.","DOI":"10.3389\/fimmu.2023.1179846"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1016\/j.molimm.2021.12.013","article-title":"Spotlight on TAP and Its Vital Role in Antigen Presentation and Cross-Presentation","volume":"142","author":"Mantel","year":"2022","journal-title":"Mol. Immunol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"102987","DOI":"10.1016\/j.jbc.2023.102987","article-title":"The Mode of Action of Tapasin on Major Histocompatibility Class I (MHC-I) Molecules","volume":"299","author":"Lan","year":"2023","journal-title":"J. Biol. Chem."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1186\/1476-4598-10-140","article-title":"Papillomavirus E5: The Smallest Oncoprotein with Many Functions","volume":"10","author":"Venuti","year":"2011","journal-title":"Mol. Cancer"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1186\/1743-422X-4-116","article-title":"The E5 Protein of the Human Papillomavirus Type 16 Down-Regulates HLA-I Surface Expression in Calnexin-Expressing but Not in Calnexin-Deficient Cells","volume":"4","author":"Gruener","year":"2007","journal-title":"Virol. J."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1675","DOI":"10.1002\/ijc.25004","article-title":"All 4 Di-Leucine Motifs in the First Hydrophobic Domain of the E5 Oncoprotein of Human Papillomavirus Type 16 Are Essential for Surface MHC Class I Downregulation Activity and E5 Endomembrane Localization","volume":"126","author":"Cortese","year":"2010","journal-title":"Int. J. Cancer"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"9241","DOI":"10.1073\/pnas.0501711102","article-title":"IFN-Gamma-Induced Immune Adaptation of the Proteasome System Is an Accelerated and Transient Response","volume":"102","author":"Heink","year":"2005","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"3033","DOI":"10.1111\/ajt.14435","article-title":"The Immunoproteasome: An Old Player with a Novel and Emerging Role in Alloimmunity","volume":"17","author":"Eskandari","year":"2017","journal-title":"Am. J. Transplant."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"994","DOI":"10.3390\/biom4040994","article-title":"Proteasome Subtypes and Regulators in the Processing of Antigenic Peptides Presented by Class I Molecules of the Major Histocompatibility Complex","volume":"4","author":"Vigneron","year":"2014","journal-title":"Biomolecules"},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Abi Habib, J., Lesenfants, J., Vigneron, N., and Van den Eynde, B.J. (2022). Functional Differences between Proteasome Subtypes. Cells, 11.","DOI":"10.3390\/cells11030421"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1016\/j.coi.2012.11.004","article-title":"The Immunoproteasome in Antigen Processing and Other Immunological Functions","volume":"25","author":"Basler","year":"2013","journal-title":"Curr. Opin. Immunol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1038\/nrclinonc.2016.206","article-title":"Proteasome Inhibitors in Cancer Therapy","volume":"14","author":"Manasanch","year":"2017","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"1976","DOI":"10.1016\/j.apsb.2022.11.005","article-title":"The Dichotomous Role of Immunoproteasome in Cancer: Friend or Foe?","volume":"13","author":"Chen","year":"2023","journal-title":"Acta Pharm. Sin. B"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"735","DOI":"10.1007\/s11596-013-1189-5","article-title":"HPV16 E5 Peptide Vaccine in Treatment of Cervical Cancer in Vitro and in Vivo","volume":"33","author":"Liao","year":"2013","journal-title":"J. Huazhong Univ. Sci. Technolog. Med. Sci."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"9083","DOI":"10.1128\/JVI.74.19.9083-9089.2000","article-title":"Induction of CD8 T Cells by Vaccination with Recombinant Adenovirus Expressing Human Papillomavirus Type 16 E5 Gene Reduces Tumor Growth","volume":"74","author":"Liu","year":"2000","journal-title":"J. Virol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1080\/21645515.2017.1264777","article-title":"HPV 16 E5 Oncoprotein Is Expressed in Early Stage Carcinogenesis and Can Be a Target of Immunotherapy","volume":"13","author":"Paolini","year":"2017","journal-title":"Hum. Vaccines Immunother."},{"key":"ref_72","doi-asserted-by":"crossref","unstructured":"Badillo-Godinez, O., Pedroza-Saavedra, A., Valverde-Gardu\u00f1o, V., Bermudez-Morales, V., Maldonado-Gama, M., Leon-Letelier, R., Bonifaz, L.C., Esquivel-Guadarrama, F., and Gutierrez-Xicotencatl, L. (2021). Induction of Therapeutic Protection in an HPV16-Associated Mouse Tumor Model Through Targeting the Human Papillomavirus-16 E5 Protein to Dendritic Cells. Front. Immunol., 12.","DOI":"10.3389\/fimmu.2021.593161"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"109946","DOI":"10.1016\/j.virol.2023.109946","article-title":"Computational and AI-Driven 3D Structural Analysis of Human Papillomavirus (HPV) Oncoproteins E5, E6, and E7 Reveal Significant Divergence of HPV E5 between Low-Risk and High-Risk Genotypes","volume":"590","author":"Jones","year":"2024","journal-title":"Virology"},{"key":"ref_74","doi-asserted-by":"crossref","unstructured":"Basukala, O., and Banks, L. (2021). The Not-So-Good, the Bad and the Ugly: HPV E5, E6 and E7 Oncoproteins in the Orchestration of Carcinogenesis. Viruses, 13.","DOI":"10.3390\/v13101892"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1038\/s41392-024-02083-w","article-title":"Roles of Human Papillomavirus in Cancers: Oncogenic Mechanisms and Clinical Use","volume":"10","author":"Zhang","year":"2025","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_76","doi-asserted-by":"crossref","unstructured":"Mlynarczyk-Bonikowska, B., and Rudnicka, L. (2024). HPV Infections-Classification, Pathogenesis, and Potential New Therapies. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25147616"},{"key":"ref_77","doi-asserted-by":"crossref","unstructured":"Kiamba, E.W., Goodier, M.R., and Clarke, E. (2025). Immune Responses to Human Papillomavirus Infection and Vaccination. Front. Immunol., 16.","DOI":"10.3389\/fimmu.2025.1591297"},{"key":"ref_78","doi-asserted-by":"crossref","unstructured":"Zhou, C., Tuong, Z.K., and Frazer, I.H. (2019). Papillomavirus Immune Evasion Strategies Target the Infected Cell and the Local Immune System. Front. Oncol., 9.","DOI":"10.3389\/fonc.2019.00682"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"600","DOI":"10.3892\/ol.2015.3295","article-title":"Effect of Human Papillomavirus Infection on the Immune System and Its Role in the Course of Cervical Cancer","volume":"10","author":"Song","year":"2015","journal-title":"Oncol. Lett."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"1896","DOI":"10.1158\/2159-8290.CD-20-1760","article-title":"Tumor Immunity and Immunotherapy for HPV-Related Cancers","volume":"11","author":"Shamseddine","year":"2021","journal-title":"Cancer Discov."},{"key":"ref_81","doi-asserted-by":"crossref","unstructured":"Mohammadi, M., Saha, A., Giles-Davis, W., Xiang, Z., Novikov, M., Hasanpourghadi, M., and Ertl, H.C.J. (2024). Preclinical Immunogenicity and Efficacy Studies for Therapeutic Vaccines for Human Papillomavirus-Type-16-Associated Cancer. Vaccines, 12.","DOI":"10.3390\/vaccines12060616"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/4\/1985\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,19]],"date-time":"2026-02-19T09:56:38Z","timestamp":1771494998000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/4\/1985"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2,19]]},"references-count":81,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2026,2]]}},"alternative-id":["ijms27041985"],"URL":"https:\/\/doi.org\/10.3390\/ijms27041985","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2,19]]}}}