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J. Mol. Sci.","IJMS"],"abstract":"<jats:p>Human papillomavirus type 16 (HPV16) is a major etiological agent of cervical and other epithelial cancers, yet the mechanisms underlying host\u2013pathogen interactions remain incompletely understood. In this study, we investigated the responses of human peripheral blood leukocytes to engineered HPV16 L1\/L2 chimeric virus-like particles (VLPs), produced in suspension by HEK 293-F cells. These VLPs were designed to mimic native viral structures while incorporating chimeric features that enhance stability and immunogenicity. Through experimental assays, we characterized leukocyte engagement, primarily involving leukocyte phenotyping, VLP internalization, confocal colocalization, and endocytic pathway analyses. We demonstrated that recombinant L1\/L2 proteins assembled into structured VLPs capable of interacting with mononuclear cells, including lymphocytes and monocytes, but not with polymorphonuclear cells, such as neutrophils, eosinophils and basophils. Uptake occurred via the CD71 transferrin receptor-mediated pathway, in addition to other endocytic routes analyzed, as confirmed by blockage assays using chlorpromazine, rCTB, filipin, nystatin, liquemine, and sodium azide. Confocal colocalization and endocytic pathway analyses further supported receptor-mediated uptake. These findings demonstrate that HPV16 L1\/L2 chimeric VLPs interact with and are internalized by human peripheral blood mononuclear cells through CD71-associated and other endocytic pathways. The study provides new insights into HPV16 VLP\u2013leukocyte interactions and contributes to a better understanding of the cellular mechanisms involved in VLP uptake, which may be relevant for future studies on HPV biology and VLP-based vaccine development.<\/jats:p>","DOI":"10.3390\/ijms27156968","type":"journal-article","created":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T12:57:56Z","timestamp":1785761876000},"page":"6968","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Experimental Analysis of HPV16 L1\/L2 Chimeric VLP Internalization by Human Peripheral Blood Leukocytes"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0676-9190","authenticated-orcid":false,"given":"Aurora Marques","family":"Cianciarullo","sequence":"first","affiliation":[{"name":"Laboratory of Genetics, Butantan Institute, Secretary of Sao Paulo State for Health, 1500 Dr. Vital Brazil Avenue, Sao Paulo 05503-900, Brazil"},{"name":"Program of Postgraduate Interunit in Biotechnology USP-IBU-IPT, Institute of Biomedical Sciences, University of Sao Paulo, 2415 Prof Lineu Prestes Avenue, University City, Sao Paulo 05508-900, Brazil"},{"name":"Program of Professional Upgrading at Butantan Institute, Secretary of Sao Paulo State for Health, 188 Dr. Eneas de Carvalho Aguiar, Sao Paulo 05403-000, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dirce","family":"Sakauchi","sequence":"additional","affiliation":[{"name":"Laboratory of Genetics, Butantan Institute, Secretary of Sao Paulo State for Health, 1500 Dr. Vital Brazil Avenue, Sao Paulo 05503-900, Brazil"},{"name":"Program of Postgraduate Interunit in Biotechnology USP-IBU-IPT, Institute of Biomedical Sciences, University of Sao Paulo, 2415 Prof Lineu Prestes Avenue, University City, Sao Paulo 05508-900, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erica Akemi Kavati","family":"Sasaki","sequence":"additional","affiliation":[{"name":"Laboratory of Genetics, Butantan Institute, Secretary of Sao Paulo State for Health, 1500 Dr. Vital Brazil Avenue, Sao Paulo 05503-900, Brazil"},{"name":"Program of Postgraduate Interunit in Biotechnology USP-IBU-IPT, Institute of Biomedical Sciences, University of Sao Paulo, 2415 Prof Lineu Prestes Avenue, University City, Sao Paulo 05508-900, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tania Matiko","family":"Hosoda","sequence":"additional","affiliation":[{"name":"Laboratory of Genetics, Butantan Institute, Secretary of Sao Paulo State for Health, 1500 Dr. Vital Brazil Avenue, Sao Paulo 05503-900, Brazil"},{"name":"Program of Professional Upgrading at Butantan Institute, Secretary of Sao Paulo State for Health, 188 Dr. Eneas de Carvalho Aguiar, Sao Paulo 05403-000, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Primavera","family":"Borelli","sequence":"additional","affiliation":[{"name":"Laboratory of Experimental and Clinical Hematology, Department of Clinical and Toxicological Analyses, School of Pharmaceutical Sciences, University of Sao Paulo, 580 B17 Prof Lineu Prestes Avenue, University City, Sao Paulo 05508-900, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Willy","family":"Be\u00e7ak","sequence":"additional","affiliation":[{"name":"Laboratory of Genetics, Butantan Institute, Secretary of Sao Paulo State for Health, 1500 Dr. Vital Brazil Avenue, Sao Paulo 05503-900, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"650","DOI":"10.1002\/ijc.2910130509","article-title":"Attempts to Detect Virus-specific DNA in Human Tumors. I. Nucleic Acid Hybridizations with Complementary RNA of Human Wart Virus","volume":"13","author":"Meinhof","year":"1974","journal-title":"Intl J. Cancer"},{"key":"ref_2","first-page":"794","article-title":"Condylomata Acuminata and Human Genital Cancer","volume":"36","year":"1976","journal-title":"Cancer Res."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1070","DOI":"10.1073\/pnas.84.4.1070","article-title":"Papillomavirus Sequences Integrate near Cellular Oncogenes in Some Cervical Carcinomas","volume":"84","author":"Croce","year":"1987","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1016\/j.coviro.2017.07.014","article-title":"Human Papillomaviruses and Carcinogenesis: Well-Established and Novel Models","volume":"26","author":"Viarisio","year":"2017","journal-title":"Curr. Opin. Virol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"e01403-22","DOI":"10.1128\/jcm.01403-22","article-title":"Testing for Human Papillomaviruses in Urine, Blood, and Oral Specimens: An Update for the Laboratory","volume":"61","author":"Poljak","year":"2023","journal-title":"J. Clin. Microbiol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1016\/j.virol.2016.03.027","article-title":"Identification of Novel Human Papillomavirus Lineages and Sublineages in HIV\/HPV-Coinfected Pregnant Women by next-Generation Sequencing","volume":"493","author":"Siqueira","year":"2016","journal-title":"Virology"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/j.mrrev.2016.09.004","article-title":"HPV Entry into Cells","volume":"772","author":"Aksoy","year":"2017","journal-title":"Mutat. Res. Mutat. Res."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"164","DOI":"10.30574\/gscbps.2023.25.1.0430","article-title":"Human Papillomavirus Infection Associated with Cervical Cancer and Other Malignancies","volume":"25","author":"Sakauchi","year":"2023","journal-title":"GSC Biol. Pharm. Sci."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"H1","DOI":"10.1016\/j.vaccine.2013.10.003","article-title":"Comprehensive Control of Human Papillomavirus Infections and Related Diseases","volume":"31","author":"Bosch","year":"2013","journal-title":"Vaccine"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1002\/ijc.28963","article-title":"Human Papillomavirus DNA Prevalence and Type Distribution in Anal Carcinomas Worldwide: HPV in Anal Cancers","volume":"136","author":"Alemany","year":"2015","journal-title":"Int. J. Cancer"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Mlynarczyk-Bonikowska, B., and Rudnicka, L. (2024). HPV Infections\u2014Classification, Pathogenesis, and Potential New Therapies. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25147616"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"7260","DOI":"10.1128\/jvi.68.11.7260-7266.1994","article-title":"Interaction of Papillomaviruses with the Cell Surface","volume":"68","author":"Roden","year":"1994","journal-title":"J. Virol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"7570","DOI":"10.1128\/jvi.68.11.7570-7574.1994","article-title":"Neutralization of Bovine Papillomavirus by Antibodies to L1 and L2 Capsid Proteins","volume":"68","author":"Roden","year":"1994","journal-title":"J. Virol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"9201","DOI":"10.1128\/JVI.75.19.9201-9209.2001","article-title":"Enhancement of Capsid Gene Expression: Preparing the Human Papillomavirus Type 16 Major Structural Gene L1 for DNA Vaccination Purposes","volume":"75","author":"Leder","year":"2001","journal-title":"J. Virol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"9311","DOI":"10.1073\/pnas.0504020102","article-title":"Production of Infectious Human Papillomavirus Independently of Viral Replication and Epithelial Cell Differentiation","volume":"102","author":"Pyeon","year":"2005","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_16","first-page":"1073","article-title":"Production of HPV16 L1L2 VLPs in Cultures of Human Epithelial Cells","volume":"2","author":"Cianciarullo","year":"2010","journal-title":"Microsc. Sci. Technol. Appl. Educ."},{"key":"ref_17","first-page":"617","article-title":"Interaction of HPV16L1L2 VLP with Stem Cells CD34+\/CD117+ of the Human Amniotic Fluid","volume":"1","author":"Kavati","year":"2012","journal-title":"Curr. Microsc. Contrib. Adv. Sci. Technol."},{"key":"ref_18","first-page":"678","article-title":"Intracellular Distribution of Recombinant Human Papillomavirus Capsid Proteins","volume":"1","author":"Marigliani","year":"2012","journal-title":"Curr. Microsc. Contrib. Adv. Sci. Technol."},{"key":"ref_19","first-page":"69","article-title":"CDC Grand Rounds: Reducing the Burden of HPV-Associated Cancer and Disease","volume":"63","author":"Dunne","year":"2014","journal-title":"MMWR Morb. Mortal. Wkly. Rep."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"258","DOI":"10.30574\/wjarr.2021.9.3.0094","article-title":"Production of HPV16 Capsid Proteins in Suspension Cultures of Human Epithelial Cells","volume":"9","author":"Sakauchi","year":"2021","journal-title":"World J. Adv. Res. Rev."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1016\/j.semradonc.2021.02.006","article-title":"Biology of HPV Mediated Carcinogenesis and Tumor Progression","volume":"31","author":"Cosper","year":"2021","journal-title":"Semin. Radiat. Oncol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"4768","DOI":"10.1016\/j.vaccine.2017.12.079","article-title":"Explanations for the High Potency of HPV Prophylactic Vaccines","volume":"36","author":"Schiller","year":"2018","journal-title":"Vaccine"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"3050","DOI":"10.1038\/s41591-023-02600-4","article-title":"Benefits, Harms and Cost-Effectiveness of Cervical Screening, Triage and Treatment Strategies for Women in the General Population","volume":"29","author":"Simms","year":"2023","journal-title":"Nat. Med."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"2513","DOI":"10.1038\/s41598-025-86943-7","article-title":"Diagnostic Accuracy of Human Papillomavirus Testing on Self-Collected Samples among Women Referred for Colposcopy","volume":"15","author":"Yan","year":"2025","journal-title":"Sci. Rep."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"e00133-26","DOI":"10.1128\/jcm.00133-26","article-title":"Urine-Based Detection of HPV for Cervical Cancer Screening: Towards Clinical Implementation","volume":"64","author":"Li","year":"2026","journal-title":"J. Clin. Microbiol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"e2300464","DOI":"10.1200\/GO.23.00464","article-title":"Human Papillomavirus-Attributable Head and Neck Cancers in India-A Systematic Review and Meta-Analysis","volume":"10","author":"Vani","year":"2024","journal-title":"JCO Glob. Oncol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1186\/s12985-026-03070-z","article-title":"The R2TP Complex Stabilises E7 to Drive Human Papillomavirus-Mediated Pathogenesis in Cellular Models of Cervical Cancer","volume":"23","author":"Shadang","year":"2026","journal-title":"Virol. J."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"888","DOI":"10.1186\/s12967-025-06896-3","article-title":"Targeting Immune Microenvironment in Cervical Cancer: Current Research and Advances","volume":"23","author":"Zhang","year":"2025","journal-title":"J. Transl. Med."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1038\/s41579-021-00617-5","article-title":"Human Papillomaviruses: Diversity, Infection and Host Interactions","volume":"20","author":"McBride","year":"2022","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"515","DOI":"10.1146\/annurev-pathmechdis-031521-041424","article-title":"Oropharyngeal Carcinoma with a Special Focus on HPV-Related Squamous Cell Carcinoma","volume":"18","author":"Ferris","year":"2023","journal-title":"Annu Rev. Pathol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"8609","DOI":"10.1038\/s41467-024-52981-4","article-title":"Human Papillomavirus-Encoded Circular RNA circE7 Promotes Immune Evasion in Head and Neck Squamous Cell Carcinoma","volume":"15","author":"Ge","year":"2024","journal-title":"Nat. Commun."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"104771","DOI":"10.1016\/j.critrevonc.2025.104771","article-title":"Role of Innate Immunity in Tumor Microenvironment of HPV-Associated Anal Cancer: The Hypothetical Beneficial Role of \u0393\u03b4 T Cells","volume":"212","author":"Capasso","year":"2025","journal-title":"Crit. Rev. Oncol."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Zhao, X., Yang, F., Mariz, F., Osen, W., Bolchi, A., Ottonello, S., and M\u00fcller, M. (2020). Combined Prophylactic and Therapeutic Immune Responses against Human Papillomaviruses Induced by a Thioredoxin-Based L2-E7 Nanoparticle Vaccine. PLoS Pathog., 16.","DOI":"10.1371\/journal.ppat.1008827"},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Jain, M., Yadav, D., Jarouliya, U., Chavda, V., Yadav, A.K., Chaurasia, B., and Song, M. (2023). Epidemiology, Molecular Pathogenesis, Immuno-Pathogenesis, Immune Escape Mechanisms and Vaccine Evaluation for HPV-Associated Carcinogenesis. Pathogens, 12.","DOI":"10.3390\/pathogens12121380"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1016\/j.ygyno.2026.01.012","article-title":"Survival Comparison Analysis between Cervical Squamous Cell Carcinoma and Adenocarcinoma with a Special Focus on the HPV Status","volume":"205","author":"Jain","year":"2026","journal-title":"Gynecol. Oncol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1016\/j.virol.2005.09.047","article-title":"Factors Influencing Subcellular Localization of the Human Papillomavirus L2 Minor Structural Protein","volume":"345","author":"Kieback","year":"2006","journal-title":"Virology"},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Oliveira, C.S., Sakauchi, D., Sasaki, E.A.K., and Cianciarullo, A.M. (2025). Recombinant Chimeric Virus-like Particles of Human Papillomavirus Produced by Distinct Cell Lineages: Potential as Prophylactic Nanovaccine and Therapeutic Drug Nanocarriers. Viruses, 17.","DOI":"10.3390\/v17091209"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1016\/j.virol.2021.07.005","article-title":"CRISPR\/Cas9-Based Inactivation of Human Papillomavirus Oncogenes E6 or E7 Induces Senescence in Cervical Cancer Cells","volume":"562","author":"Inturi","year":"2021","journal-title":"Virology"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1186\/s12985-025-02783-x","article-title":"HPV-Driven Cancers: A Looming Threat and the Potential of CRISPR\/Cas9 for Targeted Therapy","volume":"22","author":"Kermanshahi","year":"2025","journal-title":"Virol. J."},{"key":"ref_40","unstructured":"Cianciarullo, A., and Sasaki, E. (2026, March 05). Process of Producing an Immunological Composition of Prophylactic and Therapeutic DNA against HPV and Cancers Associated with the Virus, Hybrid Protein, Expression Vector, Immunological Composition and Thereof, Patent 6\/10\/2021. Available online: https:\/\/patentscope.wipo.int\/search\/pt\/detail.jsf?docId=WO2021108884&_cid=P12-MPAI67-32951-1."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Middeldorp, M., Duijster, J.W., Hoeve-Bakker, B.J.A., Berkhof, J., and De Melker, H.E. (2026). The Long-Term Effect of 2 and 3 Doses of Bivalent HPV Vaccination Against HPV Infections: A Comparison Between 2 Observational Cohort Studies. J. Infect. Dis., jiag167.","DOI":"10.1093\/infdis\/jiag167"},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Li, J.-X., Zhang, J., Li, C.-H., Zhang, Q., Kong, B., and Wang, P.-H. (2025). Human Papillomavirus E2 Proteins Suppress Innate Antiviral Signaling Pathways. Front Immunol., 16.","DOI":"10.3389\/fimmu.2025.1555629"},{"key":"ref_43","unstructured":"Cianciarullo, A.M., Oliveira, C.S., Vicente, P.I., Sakauchi, D., and Sasaki, E.A.K. (2024). Prophylactic and Therapeutic Vaccines Against HPV and Associated Cancers, Editora CRV."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1002\/rmv.1822","article-title":"Human Papillomavirus Molecular Biology and Disease Association","volume":"25","author":"Doorbar","year":"2015","journal-title":"Rev. Med. Virol."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Viarisio, D., M\u00fcller-Decker, K., Accardi, R., Robitaille, A., D\u00fcrst, M., Beer, K., Jansen, L., Flechtenmacher, C., Bozza, M., and Harbottle, R. (2018). Beta HPV38 Oncoproteins Act with a Hit-and-Run Mechanism in Ultraviolet Radiation-Induced Skin Carcinogenesis in Mice. PLoS Pathog., 14.","DOI":"10.1371\/journal.ppat.1006783"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"354","DOI":"10.1016\/j.ygyno.2019.05.024","article-title":"Age-Specific HPV Type Distribution in High-Grade Cervical Disease in Screened and Unvaccinated Women","volume":"154","author":"Aro","year":"2019","journal-title":"Gynecol. Oncol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1016\/j.virusres.2016.11.020","article-title":"Developments in L2-Based Human Papillomavirus (HPV) Vaccines","volume":"231","author":"Schellenbacher","year":"2017","journal-title":"Virus Res."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/j.ejca.2014.10.016","article-title":"Incidence of Human Papillomavirus Positive Tonsillar and Base of Tongue Carcinoma: A Stabilisation of an Epidemic of Viral Induced Carcinoma?","volume":"51","author":"Nordfors","year":"2015","journal-title":"Eur. J. Cancer"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1016\/j.oraloncology.2018.05.001","article-title":"Human Papillomavirus Detection in Gargles, Tonsil Brushings, and Frozen Tissues in Cancer-Free Patients","volume":"82","author":"Combes","year":"2018","journal-title":"Oral Oncol."},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Gheit, T., Rollo, F., Brancaccio, R.N., Robitaille, A., Galati, L., Giuliani, M., Latini, A., Pichi, B., Benevolo, M., and Cuenin, C. (2020). Oral Infection by Mucosal and Cutaneous Human Papillomaviruses in the Men Who Have Sex with Men from the OHMAR Study. Viruses, 12.","DOI":"10.3390\/v12080899"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1038\/nrm1959","article-title":"Mechanisms of Pathogen Entry through the Endosomal Compartments","volume":"7","author":"Gruenberg","year":"2006","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Kinlock, B.L., Wang, Y., Turner, T.M., Wang, C., and Liu, B. (2014). Transcytosis of HIV-1 through Vaginal Epithelial Cells Is Dependent on Trafficking to the Endocytic Recycling Pathway. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0096760"},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Moody, C.A. (2022). Regulation of the Innate Immune Response during the Human Papillomavirus Life Cycle. Viruses, 14.","DOI":"10.3390\/v14081797"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"110266","DOI":"10.1016\/j.virol.2024.110266","article-title":"The Roles of DNA Damage Repair and Innate Immune Surveillance Pathways in HPV Pathogenesis","volume":"600","author":"Kono","year":"2024","journal-title":"Virology"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.virusres.2016.10.015","article-title":"Cruising the Cellular Highways: How Human Papillomavirus Travels from the Surface to the Nucleus","volume":"231","author":"DiGiuseppe","year":"2017","journal-title":"Virus Res."},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Hoppe-Seyler, K., M\u00e4ndl, J., Adrian, S., Kuhn, B., and Hoppe-Seyler, F. (2017). Virus\/Host Cell Crosstalk in Hypoxic HPV-Positive Cancer Cells. Viruses, 9.","DOI":"10.3390\/v9070174"},{"key":"ref_57","first-page":"665","article-title":"A Simple, Fast, Inexpensive and Efficient Method for Leukocytes Separation with Preservation of Morphology and Cell Viability for Use in Education and Research","volume":"1","author":"Kavati","year":"2017","journal-title":"Microsc. Imaging Sci. Pract. Approaches To Appl. Res. Educ."},{"key":"ref_58","first-page":"6898","article-title":"Association of Bovine Papillomavirus Type 2 and Bracken Fern with Bladder Cancer in Cattle","volume":"52","author":"Campo","year":"1992","journal-title":"Cancer Res."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"2127","DOI":"10.1099\/0022-1317-79-9-2127","article-title":"Bovine Papillomavirus Transmission and Chromosomal Aberrations: An Experimental Model","volume":"79","author":"Birgel","year":"1998","journal-title":"J. General. Virol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/0002-9378(92)91825-U","article-title":"Possible Transplacental Transmission of Human Papillomaviruses","volume":"166","author":"Tseng","year":"1992","journal-title":"Am. J. Obstet. Gynecol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"406","DOI":"10.1006\/gyno.1993.1071","article-title":"Detection of Human Papillomavirus Type 16 in Plasma Cells","volume":"48","author":"Payne","year":"1993","journal-title":"Gynecol. Oncol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"540","DOI":"10.1093\/ajcp\/95.4.540","article-title":"Identification of Human Papillomavirus DNA Sequences in Peripheral Blood Mononuclear Cells","volume":"95","author":"Pao","year":"1991","journal-title":"Am. J. Clin. Pathol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"843","DOI":"10.1046\/j.1523-1747.1998.00172.x","article-title":"HPV Sequences in Blood of Patients with Condyloma Acuminata","volume":"110","author":"Karas","year":"1998","journal-title":"J. Investig. Dermatol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"S648","DOI":"10.1093\/infdis\/jiu537","article-title":"Modeling Mucosal Cell-Associated HIV Type 1 Transmission in Vitro","volume":"210","author":"Anderson","year":"2014","journal-title":"J. Infect. Dis."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.coviro.2018.06.001","article-title":"Collective Properties of Viral Infectivity","volume":"33","year":"2018","journal-title":"Curr. Opin. Virol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"3039","DOI":"10.1073\/pnas.78.5.3039","article-title":"Human Cell Surface Glycoprotein Related to Cell Proliferation Is the Receptor for Transferrin","volume":"78","author":"Trowbridge","year":"1981","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"871","DOI":"10.1152\/physrev.00001.2003","article-title":"Transcytosis: Crossing Cellular Barriers","volume":"83","author":"Tuma","year":"2003","journal-title":"Physiol. Rev."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1007\/s10930-009-9208-x","article-title":"Computational Structure Models of Apo and Diferric Transferrin\u2013Transferrin Receptor Complexes","volume":"28","author":"Sakajiri","year":"2009","journal-title":"Protein J."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"e00168-17","DOI":"10.1128\/JVI.00168-17","article-title":"Interferon Gamma Prevents Infectious Entry of Human Papillomavirus 16 via an L2-Dependent Mechanism","volume":"91","author":"Day","year":"2017","journal-title":"J. Virol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"2821","DOI":"10.1099\/jgv.0.000954","article-title":"The Cellular Endosomal Protein Stannin Inhibits Intracellular Trafficking of Human Papillomavirus during Virus Entry","volume":"98","author":"Lipovsky","year":"2017","journal-title":"J. General. Virol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1093\/cid\/ciw354","article-title":"Impact and Effectiveness of the Quadrivalent Human Papillomavirus Vaccine: A Systematic Review of 10 Years of Real-World Experience","volume":"63","author":"Garland","year":"2016","journal-title":"Clin. Infect. Dis."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1016\/j.ygyno.2019.02.016","article-title":"HPV Infections and Cytologic Abnormalities in Vaccinated Women 21\u201334 Years of Age: Results from the Baseline Phase of the Onclarity Trial","volume":"153","author":"Wright","year":"2019","journal-title":"Gynecol. Oncol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"100191","DOI":"10.1016\/j.pvr.2019.100191","article-title":"IPVS Policy Statement Addressing the Burden of HPV Disease for Indigenous Peoples","volume":"9","author":"Lawton","year":"2020","journal-title":"Papillomavirus Res."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"mjac021","DOI":"10.1093\/jmcb\/mjac021","article-title":"SARS-CoV-2 Productively Infects Primary Human Immune System Cells in Vitro and in COVID-19 Patients","volume":"14","author":"Pontelli","year":"2022","journal-title":"J. Mol. Cell Biol."},{"key":"ref_75","doi-asserted-by":"crossref","unstructured":"Gravitt, P., and Winer, R. (2017). Natural History of HPV Infection across the Lifespan: Role of Viral Latency. Viruses, 9.","DOI":"10.3390\/v9100267"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"1108","DOI":"10.1080\/22221751.2019.1637072","article-title":"Papillomavirus Can Be Transmitted through the Blood and Produce Infections in Blood Recipients: Evidence from Two Animal Models","volume":"8","author":"Cladel","year":"2019","journal-title":"Emerg. Microbes Infect."},{"key":"ref_77","doi-asserted-by":"crossref","unstructured":"Maswanganye, C.K., Mkhize, P.P., and Matume, N.D. (2024). Mapping the HPV Landscape in South African Women: A Systematic Review and Meta-Analysis of Viral Genotypes, Microbiota, and Immune Signals. Viruses, 16.","DOI":"10.3390\/v16121893"},{"key":"ref_78","doi-asserted-by":"crossref","unstructured":"Williamson, A.-L. (2023). Recent Developments in Human Papillomavirus (HPV) Vaccinology. Viruses, 15.","DOI":"10.3390\/v15071440"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1016\/j.ajog.2025.02.029","article-title":"An Updated Understanding of the Natural History of Cervical Human Papillomavirus Infection\u2014Clinical Implications","volume":"232","author":"Lycke","year":"2025","journal-title":"Am. J. Obstet. Gynecol."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1002\/jbm.a.30141","article-title":"HEK 293 Cell Suspension Culture Using Fibronectin-adsorbed Polymer Nanospheres in Serum-free Medium","volume":"71A","author":"Ryu","year":"2004","journal-title":"J. Biomed. Mater. Res."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1016\/j.copbio.2021.05.001","article-title":"Molecular Characterization of HEK293 Cells as Emerging Versatile Cell Factories","volume":"71","author":"Pulix","year":"2021","journal-title":"Curr. Opin. Biotechnol."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1016\/S0076-6879(09)63015-9","article-title":"Chapter 15 Recombinant Protein Production by Transient Gene Transfer into Mammalian Cells","volume":"Volume 463","author":"Geisse","year":"2009","journal-title":"Methods in Enzymology"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"1144","DOI":"10.1007\/s00253-006-0409-3","article-title":"Suspended Aggregates as an Immobilization Mode for High-Density Perfusion Culture of HEK 293 Cells in a Stirred Tank Bioreactor","volume":"72","author":"Liu","year":"2006","journal-title":"Appl. Microbiol. Biotechnol."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"1110","DOI":"10.3109\/07388551.2015.1084266","article-title":"Human Cell Lines for Biopharmaceutical Manufacturing: History, Status, and Future Perspectives","volume":"36","author":"Dumont","year":"2016","journal-title":"Crit. Rev. Biotechnol."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1186\/1743-422X-9-52","article-title":"Disassembly and Reassembly of Human Papillomavirus Virus-like Particles Produces More Virion-like Antibody Reactivity","volume":"9","author":"Zhao","year":"2012","journal-title":"Virol. J."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1099\/0022-1317-36-1-59","article-title":"Characteristics of a Human Cell Line Transformed by DNA from Human Adenovirus Type 5","volume":"36","author":"Graham","year":"1977","journal-title":"J. General. Virol."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1016\/S0022-2836(83)80284-8","article-title":"Studies on Transformation of Escherichia Coli with Plasmids","volume":"166","author":"Hanahan","year":"1983","journal-title":"J. Mol. Biol."},{"key":"ref_88","unstructured":"Sambrook, J., and Russell, D.W. (2001). Molecular Cloning: A Laboratory Manual, Cold Spring Harbor Laboratory Press. [3rd ed.]."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"680","DOI":"10.1038\/227680a0","article-title":"Cleavage of Structural Proteins during the Assembly of the Head of Bacteriophage T4","volume":"227","author":"Laemmli","year":"1970","journal-title":"Nature"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1016\/0165-022X(94)90020-5","article-title":"A Simple Modification of Blum\u2019s Silver Stain Method Allows for 30 Minute Detection of Proteins in Polyacrylamide Gels","volume":"28","author":"Nesterenko","year":"1994","journal-title":"J. Biochem. Biophys. Methods"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"3652","DOI":"10.1016\/S0264-410X(01)00086-X","article-title":"Pre-Clinical Safety and Efficacy of TA-CIN, a Recombinant HPV16 L2E6E7 Fusion Protein Vaccine, in Homologous and Heterologous Prime-Boost Regimens","volume":"19","author":"Kappenberg","year":"2001","journal-title":"Vaccine"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"745","DOI":"10.1128\/AEM.72.1.745-752.2006","article-title":"Production of Human Papillomavirus Type 16 L1 Virus-like Particles by Recombinant Lactobacillus Casei Cells","volume":"72","author":"Aires","year":"2006","journal-title":"Appl. Env. Microbiol."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"1040","DOI":"10.1016\/j.vaccine.2008.11.099","article-title":"Vaccination with HPV16 L2E6E7 Fusion Protein in GPI-0100 Adjuvant Elicits Protective Humoral and Cell-Mediated Immunity","volume":"27","author":"Karanam","year":"2009","journal-title":"Vaccine"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1016\/j.virol.2006.05.002","article-title":"Papillomavirus Virus-like Particles Activate the PI3-Kinase Pathway via Alpha-6 Beta-4 Integrin upon Binding","volume":"352","author":"Fothergill","year":"2006","journal-title":"Virology"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"2147","DOI":"10.1099\/vir.0.2008\/002212-0","article-title":"Clathrin- and Caveolae-Independent Entry of Feline Infectious Peritonitis Virus in Monocytes Depends on Dynamin","volume":"89","author":"Dewerchin","year":"2008","journal-title":"J. General. Virol."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/15\/6968\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T04:38:20Z","timestamp":1785904700000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/15\/6968"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,3]]},"references-count":95,"journal-issue":{"issue":"15","published-online":{"date-parts":[[2026,8]]}},"alternative-id":["ijms27156968"],"URL":"https:\/\/doi.org\/10.3390\/ijms27156968","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,3]]}}}