{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,27]],"date-time":"2026-04-27T20:00:38Z","timestamp":1777320038646,"version":"3.51.4"},"reference-count":89,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2023,11,3]],"date-time":"2023-11-03T00:00:00Z","timestamp":1698969600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Asklepios Gilead Hellas"},{"name":"IKY doctoral fellowship"},{"name":"Hellenic Pasteur Institute"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Hepatitis C virus (HCV) alters gene expression epigenetically to rearrange the cellular microenvironment in a beneficial way for its life cycle. The host epigenetic changes induced by HCV lead to metabolic dysfunction and malignant transformation. Lysine-specific demethylase 1 (LSD1) is an epigenetic controller of critical cellular functions that are essential for HCV propagation. We investigated the putative role of LSD1 in the establishment of HCV infection using genetic engineering and pharmacological inhibition to alter endogenous LSD1 levels. We demonstrated for the first time that HCV replication was inhibited in LSD1-overexpressing cells, while specific HCV proteins differentially fine-tuned endogenous LSD1 expression levels. Electroporation of the full-length HCV genome and subgenomic replicons in LSD1 overexpression enhanced translation and partially restored HCV replication, suggesting that HCV might be inhibited by LSD1 during the early steps of infection. Conversely, the inhibition of LSD1, followed by HCV infection in vitro, increased viral replication. LSD1 was shown to participate in an intriguing antiviral mechanism, where it activates endolysosomal interferon-induced transmembrane protein 3 (IFITM3) via demethylation, leading endocytosed HCV virions to degradation. Our study proposes that HCV-mediated LSD1 oscillations over countless viral life cycles throughout chronic HCV infection may promote epigenetic changes related to HCV-induced hepatocarcinogenesis.<\/jats:p>","DOI":"10.3390\/cells12212568","type":"journal-article","created":{"date-parts":[[2023,11,3]],"date-time":"2023-11-03T10:51:28Z","timestamp":1699008688000},"page":"2568","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["The Epigenetic Controller Lysine-Specific Demethylase 1 (LSD1) Regulates the Outcome of Hepatitis C Viral Infection"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6843-6546","authenticated-orcid":false,"given":"Georgia","family":"Papadopoulou","sequence":"first","affiliation":[{"name":"Molecular Virology Laboratory, Hellenic Pasteur Institute, 11521 Athens, Greece"},{"name":"Division of Animal and Human Physiology, Department of Biology, National and Kapodistrian University of Athens, 15784 Athens, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stavroula","family":"Petroulia","sequence":"additional","affiliation":[{"name":"Molecular Virology Laboratory, Hellenic Pasteur Institute, 11521 Athens, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eirini","family":"Karamichali","sequence":"additional","affiliation":[{"name":"Molecular Virology Laboratory, Hellenic Pasteur Institute, 11521 Athens, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1826-1423","authenticated-orcid":false,"given":"Alexios","family":"Dimitriadis","sequence":"additional","affiliation":[{"name":"Molecular Biology and Immunobiotechnology Laboratory, Hellenic Pasteur Institute, 11521 Athens, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dimitrios","family":"Marousis","sequence":"additional","affiliation":[{"name":"Molecular Virology Laboratory, Hellenic Pasteur Institute, 11521 Athens, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elisavet","family":"Ioannidou","sequence":"additional","affiliation":[{"name":"Molecular Virology Laboratory, Hellenic Pasteur Institute, 11521 Athens, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Panagiota","family":"Papazafiri","sequence":"additional","affiliation":[{"name":"Division of Animal and Human Physiology, Department of Biology, National and Kapodistrian University of Athens, 15784 Athens, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John","family":"Koskinas","sequence":"additional","affiliation":[{"name":"2nd Department of Internal Medicine, Medical School of Athens, Hippokration General Hospital, 11521 Athens, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6888-7678","authenticated-orcid":false,"given":"Pelagia","family":"Foka","sequence":"additional","affiliation":[{"name":"Molecular Virology Laboratory, Hellenic Pasteur Institute, 11521 Athens, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2784-3695","authenticated-orcid":false,"given":"Urania","family":"Georgopoulou","sequence":"additional","affiliation":[{"name":"Molecular Virology Laboratory, Hellenic Pasteur Institute, 11521 Athens, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,11,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1016\/bs.mie.2016.01.020","article-title":"LSD1 Histone Demethylase Assays and Inhibition","volume":"573","author":"Hayward","year":"2016","journal-title":"Methods Enzymol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1936","DOI":"10.1038\/s12276-020-00542-2","article-title":"LSD1: More than demethylation of histone lysine residues","volume":"52","author":"Perillo","year":"2020","journal-title":"Exp. Mol. Med."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1038\/nature06092","article-title":"p53 is regulated by the lysine demethylase LSD1","volume":"449","author":"Huang","year":"2007","journal-title":"Nature"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1032","DOI":"10.1002\/med.21350","article-title":"A Systematic Review of Histone Lysine-Specific Demethylase 1 and Its Inhibitors","volume":"35","author":"Zheng","year":"2015","journal-title":"Med. Res. Rev."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1103","DOI":"10.2217\/epi-2016-0009","article-title":"LSD1: Biologic roles and therapeutic targeting","volume":"8","author":"Somervaille","year":"2016","journal-title":"Epigenomics"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1186\/s13045-019-0811-9","article-title":"LSD1\/KDM1A inhibitors in clinical trials: Advances and prospects","volume":"12","author":"Fang","year":"2019","journal-title":"J. Hematol. Oncol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"6651","DOI":"10.3748\/wjg.v18.i45.6651","article-title":"Overexpression of lysine specific demethylase 1 predicts worse prognosis in primary hepatocellular carcinoma patients","volume":"18","author":"Zhao","year":"2012","journal-title":"World J. Gastroenterol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1170","DOI":"10.1016\/j.jhep.2020.08.018","article-title":"EASL recommendations on treatment of hepatitis C: Final update of the series\u2606","volume":"73","author":"Pawlotsky","year":"2020","journal-title":"J. Hepatol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"e00974-20","DOI":"10.1128\/JVI.00974-20","article-title":"Antiviral Properties of the LSD1 Inhibitor SP-2509","volume":"94","author":"Harancher","year":"2020","journal-title":"J. Virol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"25901","DOI":"10.1038\/srep25901","article-title":"The enzymes LSD1 and Set1A cooperate with the viral protein HBx to establish an active hepatitis B viral chromatin state","volume":"6","author":"Alarcon","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Hu, Q.-X., Wang, H.-Y., Jiang, L., Wang, C.-Y., Ju, L.-G., Zhu, Y., Zhong, B., Wu, M., Wang, Z., and Li, L.-Y. (2021). Histone demethylase LSD1 promotes RIG-I poly-ubiquitination and anti-viral gene expression. PLoS Pathog., 17.","DOI":"10.1371\/journal.ppat.1009918"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Shan, J., Zhao, B., Shan, Z., Nie, J., Deng, R., Xiong, R., Tsun, A., Pan, W., Zhao, H., and Chen, L. (2017). Histone demethylase LSD1 restricts influenza A virus infection by erasing IFITM3-K88 monomethylation. PLoS Pathog., 13.","DOI":"10.1371\/journal.ppat.1006773"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"688","DOI":"10.1038\/nrmicro3098","article-title":"The ins and outs of hepatitis C virus entry and assembly","volume":"11","author":"Lindenbach","year":"2013","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Foka, P., Dimitriadis, A., Karamichali, E., Kochlios, E., Eliadis, P., Valiakou, V., Koskinas, J., Mamalaki, A., and Georgopoulou, U. (2021). HCV-Induced Immunometabolic Crosstalk in a Triple-Cell Co-Culture Model Capable of Simulating Systemic Iron Homeostasis. Cells, 10.","DOI":"10.3390\/cells10092251"},{"key":"ref_15","unstructured":"World Health Organization (2023, September 01). Hepatitis C. Available online: https:\/\/www.who.int\/news-room\/fact-sheets\/detail\/hepatitis-c."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"101575","DOI":"10.1016\/j.clinre.2020.11.005","article-title":"Hepatitis C virus-related vasculitis","volume":"45","author":"Boleto","year":"2021","journal-title":"Clin. Res. Hepatol. Gastroenterol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1764","DOI":"10.12998\/wjcc.v10.i6.1764","article-title":"Association between direct-acting antiviral agents in hepatitis C virus treatment and hepatocellular carcinoma occurrence and recurrence: The endless debate","volume":"10","author":"Kamal","year":"2022","journal-title":"World J. Clin. Cases"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Brozzetti, S., Tancredi, M., Bini, S., De Lucia, C., Antimi, J., D\u2019Alterio, C., De Sanctis, G.M., Furlan, C., Malpassuti, V.C., and Lucatelli, P. (2021). HCC in the Era of Direct-Acting Antiviral Agents (DAAs): Surgical and Other Curative or Palliative Strategies in the Elderly. Cancers, 13.","DOI":"10.3390\/cancers13123025"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1016\/bs.acr.2020.10.003","article-title":"Hepatitis C virus associated hepatocellular carcinoma","volume":"149","author":"Khatun","year":"2021","journal-title":"Adv. Cancer Res."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Zaki, M.Y.W., Fathi, A.M., Samir, S., Eldafashi, N., William, K.Y., Nazmy, M.H., Fathy, M., Gill, U.S., and Shetty, S. (2022). Innate and Adaptive Immunopathogeneses in Viral Hepatitis; Crucial Determinants of Hepatocellular Carcinoma. Cancers, 14.","DOI":"10.3390\/cancers14051255"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Da Silva, M.L.R., De Albuquerque, B.H.D.R., Allyrio, T.A.D.M.F., De Almeida, V.D., Cobucci, R.N.D.O., Bezerra, F.L., Andrade, V.S., Lanza, D.C.F., De Azevedo, J.C.V., and De Ara\u00fajo, J.M.G. (2021). The role of HPV-induced epigenetic changes in cervical carcinogenesis (Review). Biomed. Rep., 15.","DOI":"10.3892\/br.2021.1436"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"741","DOI":"10.1007\/s12072-022-10351-6","article-title":"Hepatitis B virus X protein mediated epigenetic alterations in the pathogenesis of hepatocellular carcinoma","volume":"16","author":"Yang","year":"2022","journal-title":"Hepatol. Int."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Perez, S., Kaspi, A., Domovitz, T., Davidovich, A., Lavi-Itzkovitz, A., Meirson, T., Alison Holmes, J., Dai, C.-Y., Huang, C.-F., and Chung, R.T. (2019). Hepatitis C virus leaves an epigenetic signature post cure of infection by direct-acting antivirals. PLoS Genet., 15.","DOI":"10.1371\/journal.pgen.1008181"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"13001","DOI":"10.1128\/JVI.76.24.13001-13014.2002","article-title":"Highly permissive cell lines for subgenomic and genomic hepatitis C virus RNA replication","volume":"76","author":"Blight","year":"2002","journal-title":"J. Virol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"380","DOI":"10.1128\/JVI.79.1.380-392.2005","article-title":"Kissing-Loop Interaction in the 3\u2032 End of the Hepatitis C Virus Genome Essential for RNA Replication","volume":"79","author":"Friebe","year":"2005","journal-title":"J. Virol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1007\/978-1-59745-394-3_23","article-title":"Isolation of JFH-1 strain and development of an HCV infection system","volume":"510","author":"Wakita","year":"2009","journal-title":"Methods Mol. Biol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"973","DOI":"10.1053\/j.gastro.2016.07.013","article-title":"Robust HCV Genotype 3a Infectious Cell Culture System Permits Identification of Escape Variants With Resistance to Sofosbuvir","volume":"151","author":"Ramirez","year":"2016","journal-title":"Gastroenterology"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1016\/j.chom.2010.12.002","article-title":"Recruitment and activation of a lipid kinase by hepatitis C virus NS5A is essential for integrity of the membranous replication compartment","volume":"9","author":"Reiss","year":"2011","journal-title":"Cell Host Microbe"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"7034","DOI":"10.1128\/JVI.00118-08","article-title":"Efficient trans-encapsidation of hepatitis C virus RNAs into infectious virus-like particles","volume":"82","author":"Steinmann","year":"2008","journal-title":"J. Virol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"857","DOI":"10.1016\/j.molcel.2005.08.027","article-title":"Regulation of LSD1 histone demethylase activity by its associated factors","volume":"19","author":"Shi","year":"2005","journal-title":"Mol. Cell"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1016\/j.jhep.2013.08.016","article-title":"Hepatitis C virus modulates lipid regulatory factor Angiopoietin-like 3 gene expression by repressing HNF-1\u03b1 activity","volume":"60","author":"Foka","year":"2014","journal-title":"J. Hepatol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1002\/2211-5463.13048","article-title":"The Hepatitis C virus NS5A and core proteins exert antagonistic effects on HAMP gene expression: The hidden interplay with the MTF-1\/MRE pathway","volume":"11","author":"Dimitriadis","year":"2021","journal-title":"FEBS Open Bio"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"679","DOI":"10.1080\/21505594.2016.1175700","article-title":"Alterations in the iron homeostasis network: A driving force for macrophage-mediated hepatitis C virus persistency","volume":"7","author":"Foka","year":"2016","journal-title":"Virulence"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1007\/978-1-59745-394-3_11","article-title":"HCV replicons: Overview and basic protocols","volume":"510","author":"Lohmann","year":"2009","journal-title":"Methods Mol. Biol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"4243","DOI":"10.1007\/s00018-014-1621-4","article-title":"A complex signaling network involving protein kinase CK2 is required for hepatitis C virus core protein-mediated modulation of the iron-regulatory hepcidin gene expression","volume":"71","author":"Foka","year":"2014","journal-title":"Cell. Mol. Life Sci. CMLS"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"4049","DOI":"10.1016\/j.febslet.2007.07.032","article-title":"Evidence for cellular uptake of recombinant hepatitis C virus non-enveloped capsid-like particles","volume":"581","author":"Tsitoura","year":"2007","journal-title":"FEBS Lett."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1733","DOI":"10.1007\/s00705-002-0836-0","article-title":"Expression of immunoreactive forms of the hepatitis C NS5A protein in E. coli and their use for diagnostic assays","volume":"147","author":"Kalamvoki","year":"2002","journal-title":"Arch. Virol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1186\/s12943-017-0588-9","article-title":"LincRNAFEZF1-AS1 represses p21 expression to promote gastric cancer proliferation through LSD1-Mediated H3K4me2 demethylation","volume":"16","author":"Liu","year":"2017","journal-title":"Mol. Cancer"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"2491","DOI":"10.1007\/s00018-010-0351-5","article-title":"Endocytosis of hepatitis C virus non-enveloped capsid-like particles induces MAPK-ERK1\/2 signaling events","volume":"67","author":"Katsarou","year":"2010","journal-title":"Cell. Mol. Life Sci. CMLS"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"e02098-17","DOI":"10.1128\/JVI.02098-17","article-title":"Intracellular Hepatitis C Virus Modeling Predicts Infection Dynamics and Viral Protein Mechanisms","volume":"92","author":"Aunins","year":"2018","journal-title":"J. Virol."},{"key":"ref_41","first-page":"113","article-title":"HCV NS5A co-operates with PKR in modulating HCV IRES-dependent translation","volume":"26","author":"Karamichali","year":"2014","journal-title":"Infect. Genet. Evol. J. Mol. Epidemiol. Evol. Genet. Infect. Dis."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Shulla, A., and Randall, G. (2015). Spatiotemporal analysis of hepatitis C virus infection. PLoS Pathog., 11.","DOI":"10.1371\/journal.ppat.1004758"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1159\/000360830","article-title":"The HCV life cycle: In vitro tissue culture systems and therapeutic targets","volume":"32","author":"Gerold","year":"2014","journal-title":"Dig. Dis."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Valiakou, V., Eliadis, P., Karamichali, E., Tsitsilonis, O., Koskinas, J., Georgopoulou, U., and Foka, P. (2021). Differential Expression of the Host Lipid Regulators ANGPTL-3 and ANGPTL-4 in HCV Infection and Treatment. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22157961"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1284","DOI":"10.1021\/cb500018s","article-title":"A selective phenelzine analogue inhibitor of histone demethylase LSD1","volume":"9","author":"Prusevich","year":"2014","journal-title":"ACS Chem. Biol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"a036830","DOI":"10.1101\/cshperspect.a036830","article-title":"Hepatitis C Virus Entry: Protein Interactions and Fusion Determinants Governing Productive Hepatocyte Invasion","volume":"10","author":"Gerold","year":"2020","journal-title":"Cold Spring Harb. Perspect. Med."},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Bruening, J., Lasswitz, L., Banse, P., Kahl, S., Marinach, C., Vondran, F.W., Kaderali, L., Silvie, O., Pietschmann, T., and Meissner, F. (2018). Hepatitis C virus enters liver cells using the CD81 receptor complex proteins calpain-5 and CBLB. PLoS Pathog., 14.","DOI":"10.1371\/journal.ppat.1007111"},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Colpitts, C.C., Tsai, P.-L., and Zeisel, M.B. (2020). Hepatitis C Virus Entry: An Intriguingly Complex and Highly Regulated Process. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21062091"},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Jim\u00e9nez-Mungu\u00eda, I., Beaven, A.H., Blank, P.S., Sodt, A.J., and Zimmerberg, J. (2022). Interferon-induced transmembrane protein 3 (IFITM3) and its antiviral activity. Curr. Opin. Struct. Biol., 77.","DOI":"10.1016\/j.sbi.2022.102467"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"858","DOI":"10.1038\/cmi.2017.15","article-title":"IFITM3 inhibits virus-triggered induction of type I interferon by mediating autophagosome-dependent degradation of IRF3","volume":"15","author":"Jiang","year":"2018","journal-title":"Cell. Mol. Immunol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1823","DOI":"10.1002\/hep.29105","article-title":"RIG-I is a key antiviral interferon-stimulated gene against hepatitis E virus regardless of interferon production","volume":"65","author":"Xu","year":"2017","journal-title":"Hepatology"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"2313","DOI":"10.1053\/j.gastro.2019.02.038","article-title":"HCV-Induced Epigenetic Changes Associated with Liver Cancer Risk Persist after Sustained Virologic Response","volume":"156","author":"Hamdane","year":"2019","journal-title":"Gastroenterology"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"677926","DOI":"10.3389\/fonc.2021.677926","article-title":"Epigenetic Mechanisms Involved in HCV-Induced Hepatocellular Carcinoma (HCC)","volume":"11","author":"Zhao","year":"2021","journal-title":"Front. Oncol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"7408","DOI":"10.1073\/pnas.0504877103","article-title":"Construction and characterization of infectious intragenotypic and intergenotypic hepatitis C virus chimeras","volume":"103","author":"Pietschmann","year":"2006","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"001886","DOI":"10.1099\/jgv.0.001886","article-title":"Mutational analysis reveals a novel role for hepatitis C virus NS5A domain I in cyclophilin-dependent genome replication","volume":"104","author":"Chen","year":"2023","journal-title":"J. Gen. Virol."},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Domovitz, T., and Gal-Tanamy, M. (2021). Tracking Down the Epigenetic Footprint of HCV-Induced Hepatocarcinogenesis. J. Clin. Med., 10.","DOI":"10.3390\/jcm10030551"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"2108","DOI":"10.3390\/v2092108","article-title":"Oncogenic Potential of Hepatitis C Virus Proteins","volume":"2","author":"Banerjee","year":"2010","journal-title":"Viruses"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"10375","DOI":"10.1128\/JVI.00395-08","article-title":"Hepatitis C Virus Infection Induces Apoptosis through a Bax-Triggered, Mitochondrion-Mediated, Caspase 3-Dependent Pathway","volume":"82","author":"Deng","year":"2008","journal-title":"J. Virol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1215","DOI":"10.1515\/hsz-2015-0172","article-title":"Hepatitis C Virus and Autophagy","volume":"396","author":"Wang","year":"2015","journal-title":"Biol. Chem."},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Sidorkiewicz, M. (2021). Hepatitis C Virus Uses Host Lipids to Its Own Advantage. Metabolites, 11.","DOI":"10.3390\/metabo11050273"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1016\/j.biochi.2017.06.009","article-title":"Interplay between hepatitis C virus and lipid metabolism during virus entry and assembly","volume":"141","author":"Lavie","year":"2017","journal-title":"Biochimie"},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Cosset, F.-L., Mialon, C., Boson, B., Granier, C., and Denolly, S. (2020). HCV Interplay with Lipoproteins: Inside or Outside the Cells?. Viruses, 12.","DOI":"10.3390\/v12040434"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"29937","DOI":"10.1074\/jbc.M114.573659","article-title":"Regulation of lipogenic gene expression by lysine-specific histone demethylase-1 (LSD1)","volume":"289","author":"Abdulla","year":"2014","journal-title":"J. Biol. Chem."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1038\/s41392-022-00927-x","article-title":"LSD1 is required for euchromatic origin firing and replication timing","volume":"7","author":"Wang","year":"2022","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1080\/15548627.2018.1520546","article-title":"Histone methyl-transferases and demethylases in the autophagy regulatory network: The emerging role of KDM1A\/LSD1 demethylase","volume":"15","author":"Ambrosio","year":"2018","journal-title":"Autophagy"},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Karakaidos, P., Verigos, J., and Magklara, A. (2019). LSD1\/KDM1A, a Gate-Keeper of Cancer Stemness and a Promising Therapeutic Target. Cancers, 11.","DOI":"10.3390\/cancers11121821"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"654998","DOI":"10.3389\/fimmu.2021.654998","article-title":"HCV Core Protein Induces Chemokine CCL2 and CXCL10 Expression Through NF-\u03baB Signaling Pathway in Macrophages","volume":"12","author":"Song","year":"2021","journal-title":"Front. Immunol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"2472","DOI":"10.1038\/sj.onc.1207368","article-title":"Modulation of p53 transcription regulatory activity and post-translational modification by hepatitis C virus core protein","volume":"23","author":"Kao","year":"2004","journal-title":"Oncogene"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"4801","DOI":"10.1038\/sj.onc.1205589","article-title":"HCV NS5A interacts with p53 and inhibits p53-mediated apoptosis","volume":"21","author":"Lan","year":"2002","journal-title":"Oncogene"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"17775","DOI":"10.1074\/jbc.M210900200","article-title":"The hepatitis C virus non-structural NS5A protein inhibits activating protein-1 function by perturbing ras-ERK pathway signaling","volume":"278","author":"Macdonald","year":"2003","journal-title":"J. Biol. Chem."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"86681","DOI":"10.18632\/oncotarget.21407","article-title":"Hepatitis C virus core protein potentiates proangiogenic activity of hepatocellular carcinoma cells","volume":"8","author":"Shao","year":"2017","journal-title":"Oncotarget"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"791","DOI":"10.1038\/nm1268","article-title":"Production of infectious hepatitis C virus in tissue culture from a cloned viral genome","volume":"11","author":"Wakita","year":"2005","journal-title":"Nat. Med."},{"key":"ref_73","doi-asserted-by":"crossref","unstructured":"Alazard-Dany, N., Denolly, S., Boson, B., and Cosset, F.-L. (2019). Overview of HCV Life Cycle with a Special Focus on Current and Possible Future Antiviral Targets. Viruses, 11.","DOI":"10.3390\/v11010030"},{"key":"ref_74","doi-asserted-by":"crossref","unstructured":"Khan, S., Soni, S., and Veerapu, N.S. (2020). HCV Replicon Systems: Workhorses of Drug Discovery and Resistance. Front. Cell. Infect. Microbiol., 10.","DOI":"10.3389\/fcimb.2020.00325"},{"key":"ref_75","doi-asserted-by":"crossref","unstructured":"Mahesh, A., Khan, M.I.K., Govindaraju, G., Verma, M., Awasthi, S., Chavali, P.L., Chavali, S., Rajavelu, A., and Dhayalan, A. (2020). SET7\/9 interacts and methylates the ribosomal protein, eL42 and regulates protein synthesis. Biochim. Biophys. Acta BBA Mol. Cell Res., 1867.","DOI":"10.1016\/j.bbamcr.2019.118611"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"12770","DOI":"10.1074\/jbc.RA118.002890","article-title":"Identification of Rpl29 as a major substrate of the lysine methyltransferase Set7\/9","volume":"293","author":"Hamidi","year":"2018","journal-title":"J. Biol. Chem."},{"key":"ref_77","doi-asserted-by":"crossref","unstructured":"Wang, X., Zhu, J., Zhang, D., and Liu, G. (2022). Ribosomal control in RNA virus-infected cells. Front. Microbiol., 13.","DOI":"10.3389\/fmicb.2022.1026887"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"e01679-19","DOI":"10.1128\/JVI.01679-19","article-title":"Ribosomal Protein L13 Promotes IRES-Driven Translation of Foot-and-Mouth Disease Virus in a Helicase DDX3-Dependent Manner","volume":"94","author":"Han","year":"2020","journal-title":"J. Virol."},{"key":"ref_79","unstructured":"Abdulla, A. (2023, October 09). Regulation of Lipid Homeostasis by the Histone Demethylase LSD1 and Its Inhibitors. Available online: https:\/\/repository.yu.edu\/handle\/20.500.12202\/1495."},{"key":"ref_80","doi-asserted-by":"crossref","unstructured":"Vieyres, G., and Pietschmann, T. (2019). HCV Pit Stop at the Lipid Droplet: Refuel Lipids and Put on a Lipoprotein Coat before Exit. Cells, 8.","DOI":"10.3390\/cells8030233"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1038\/s41421-021-00279-w","article-title":"Targeting novel LSD1-dependent ACE2 demethylation domains inhibits SARS-CoV-2 replication","volume":"7","author":"Tu","year":"2021","journal-title":"Cell Discov."},{"key":"ref_82","doi-asserted-by":"crossref","unstructured":"Chamontin, C., Bossis, G., Nisole, S., Arhel, N.J., and Maarifi, G. (2021). Regulation of Viral Restriction by Post-Translational Modifications. Viruses, 13.","DOI":"10.3390\/v13112197"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"1506","DOI":"10.1002\/hep.30699","article-title":"Interferon-Induced Transmembrane Proteins Mediate Viral Evasion in Acute and Chronic Hepatitis C Virus Infection","volume":"70","author":"Wrensch","year":"2019","journal-title":"Hepatology"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"25946","DOI":"10.1074\/jbc.M115.657346","article-title":"The Interferon-induced Transmembrane Proteins, IFITM1, IFITM2, and IFITM3 Inhibit Hepatitis C Virus Entry","volume":"290","author":"Narayana","year":"2015","journal-title":"J. Biol. Chem."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"1740","DOI":"10.15252\/embr.201744100","article-title":"IFITM3 requires an amphipathic helix for antiviral activity","volume":"18","author":"Chesarino","year":"2017","journal-title":"EMBO Rep."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1038\/s41577-021-00626-8","article-title":"Lessons in self-defence: Inhibition of virus entry by intrinsic immunity","volume":"22","author":"Majdoul","year":"2021","journal-title":"Nat. Rev. Immunol."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"1684","DOI":"10.1158\/0008-5472.CAN-22-2433","article-title":"LSD1 Inhibition Disrupts Super-Enhancer-Driven Oncogenic Transcriptional Programs in Castration-Resistant Prostate Cancer","volume":"83","author":"Li","year":"2023","journal-title":"Cancer Res."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"eaau2922","DOI":"10.1126\/scisignal.aau2922","article-title":"Targeting NOTCH activation in small cell lung cancer through LSD1 inhibition","volume":"12","author":"Augert","year":"2019","journal-title":"Sci. Signal."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1016\/j.ccell.2018.02.002","article-title":"ORY-1001, a Potent and Selective Covalent KDM1A Inhibitor, for the Treatment of Acute Leukemia","volume":"33","author":"Maes","year":"2018","journal-title":"Cancer Cell"}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/12\/21\/2568\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T21:16:31Z","timestamp":1760130991000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/12\/21\/2568"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,11,3]]},"references-count":89,"journal-issue":{"issue":"21","published-online":{"date-parts":[[2023,11]]}},"alternative-id":["cells12212568"],"URL":"https:\/\/doi.org\/10.3390\/cells12212568","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,11,3]]}}}