{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T07:00:34Z","timestamp":1785308434472,"version":"3.55.0"},"reference-count":67,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2025,3,11]],"date-time":"2025-03-11T00:00:00Z","timestamp":1741651200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Cardiac glycosides (CGs), historically used to treat heart failure and arrhythmias, bind to the \u03b1 subunit of the Na+\/K+-ATPase pump and inhibit its activity. Their anticancer and antiviral activities are of interest. The \u03b1 subunit of the Na+\/K+-ATPase pump has four isoforms (\u03b11\u20134), each with unique tissue distribution and expression pattern; their contributions to antiviral activities have not been studied. We previously reported that CGs inhibit human CMV (HCMV) in vitro but not mouse CMV (MCMV). In addition to the low affinity of mouse \u03b11 for CGs, we hypothesized that other isoforms contribute to the anti-CMV activities of CGs. We show here that infection with HCMV significantly induced \u03b13 in human foreskin fibroblasts, while MCMV did not induce mouse \u03b13. Infection with guinea pig CMV (GPCMV) in GP fibroblasts also induced \u03b13, and CGs inhibited GPCMV replication. HCMV inhibition with digitoxin reduced \u03b13 expression. The concentration-dependent inhibition of HCMV with digitoxin analogs also correlated with \u03b13 expression. Intriguingly, \u03b13 was localized to the nucleus, and changes in its expression during infection and digitoxin treatment were mostly limited to the nucleus. At 4 h post-infection, \u03b13 colocalized with immediate early 1 (IE1) and the promyelocytic leukemia protein (PML). An interaction of \u03b13-PML-IE1 at 24 h post-infection was disrupted by digitoxin. The mRNA levels of IE1, major immediate early promoter (MIEP)-derived IE, and antiviral cytokines were reduced in infected digitoxin-treated cells. Summarized, these findings suggest a new role for \u03b13 in the anti-HCMV activities of CGs via nuclear antiviral signaling pathways.<\/jats:p>","DOI":"10.3390\/v17030398","type":"journal-article","created":{"date-parts":[[2025,3,11]],"date-time":"2025-03-11T08:59:52Z","timestamp":1741683592000},"page":"398","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Interspecies Differences in Cytomegalovirus Inhibition by Cardiac Glycosides\u2014A Unique Role of the Alpha3 Isoform of the Na+\/K+-ATPase Pump"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-6408-7611","authenticated-orcid":false,"given":"Hong","family":"Mei","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Division of Infectious Disease, Medical College of Wisconsin, Milwaukee, WI 53226, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongyi","family":"Cai","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Division of Infectious Disease, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fengjie","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Division of Infectious Disease, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rajkumar","family":"Venkatadri","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Division of Infectious Disease, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2609-4482","authenticated-orcid":false,"given":"Halli E.","family":"Miller","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Division of Infectious Disease, Medical College of Wisconsin, Milwaukee, WI 53226, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6763-2710","authenticated-orcid":false,"given":"Angela J.","family":"Mathison","sequence":"additional","affiliation":[{"name":"Department of Surgery, Division of Research and Linda T. and John A. Mellowes Center for Genomic Sciences and Precision Medicine, Medical College of Wisconsin, Milwaukee, WI 53226, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hua-Yu Leo","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Northeastern University, Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simone C.","family":"Silva","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Northeastern University, Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1699-2249","authenticated-orcid":false,"given":"George A.","family":"O\u2019Doherty","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Northeastern University, Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5363-167X","authenticated-orcid":false,"given":"Ravit","family":"Arav-Boger","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Division of Infectious Disease, Medical College of Wisconsin, Milwaukee, WI 53226, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,3,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"710","DOI":"10.1016\/S0008-6363(02)00466-2","article-title":"Myocardial Na,K-ATPase: The molecular basis for the hemodynamic effect of digoxin therapy in congestive heart failure","volume":"55","author":"Kjeldsen","year":"2002","journal-title":"Cardiovasc. Res."},{"key":"ref_2","first-page":"32","article-title":"Cardiotonic steroids on the road to anti-cancer therapy","volume":"1776","author":"Mijatovic","year":"2007","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1124\/mi.8.1.8","article-title":"Cardiac glycosides as novel cancer therapeutic agents","volume":"8","author":"Newman","year":"2008","journal-title":"Mol. Interv."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Skubnik, J., Bejcek, J., Pavlickova, V.S., and Rimpelova, S. (2021). Repurposing Cardiac Glycosides: Drugs for Heart Failure Surmounting Viruses. Molecules, 26.","DOI":"10.3390\/molecules26185627"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Caohuy, H., Eidelman, O., Chen, T., Liu, S., Yang, Q., Bera, A., Walton, N.I., Wang, T.T., and Pollard, H.B. (2021). Common cardiac medications potently inhibit ACE2 binding to the SARS-CoV-2 Spike, and block virus penetration and infectivity in human lung cells. Sci. Rep., 11.","DOI":"10.1038\/s41598-021-01690-9"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Reddy, D., Kumavath, R., Barh, D., Azevedo, V., and Ghosh, P. (2020). Anticancer and Antiviral Properties of Cardiac Glycosides: A Review to Explore the Mechanism of Actions. Molecules, 25.","DOI":"10.3390\/molecules25163596"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Amarelle, L., and Lecuona, E. (2018). The Antiviral Effects of Na,K-ATPase Inhibition: A Minireview. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19082154"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Cho, J., Lee, Y.J., Kim, J.H., Kim, S.I., Kim, S.S., Choi, B.S., and Choi, J.H. (2020). Antiviral activity of digoxin and ouabain against SARS-CoV-2 infection and its implication for COVID-19. Sci. Rep., 10.","DOI":"10.1038\/s41598-020-72879-7"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1128\/JVI.01861-17","article-title":"Digitoxin Suppresses Human Cytomegalovirus Replication via Na(+), K(+)\/ATPase alpha1 Subunit-Dependent AMP-Activated Protein Kinase and Autophagy Activation","volume":"92","author":"Mukhopadhyay","year":"2018","journal-title":"J. Virol."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Souza, E.S.K.F.C., Moraes, B.P.T., Paixao, I., Burth, P., Silva, A.R., and Goncalves-de-Albuquerque, C.F. (2021). Na(+)\/K(+)-ATPase as a Target of Cardiac Glycosides for the Treatment of SARS-CoV-2 Infection. Front. Pharmacol., 12.","DOI":"10.3389\/fphar.2021.624704"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"10715","DOI":"10.1128\/JVI.01050-16","article-title":"Convallatoxin-Induced Reduction of Methionine Import Effectively Inhibits Human Cytomegalovirus Infection and Replication","volume":"90","author":"Cohen","year":"2016","journal-title":"J. Virol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"155308","DOI":"10.1016\/j.phymed.2023.155308","article-title":"Lanatoside C inhibits herpes simplex virus 1 replication by regulating NRF2 distribution within cells","volume":"124","author":"Wu","year":"2024","journal-title":"Phytomedicine"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Schneider, N.F.Z., Cerella, C., Simoes, C.M.O., and Diederich, M. (2017). Anticancer and Immunogenic Properties of Cardiac Glycosides. Molecules, 22.","DOI":"10.3390\/molecules22111932"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"2495","DOI":"10.1007\/s00705-006-0824-x","article-title":"Ionic Contra-Viral Therapy (ICVT); a new approach to the treatment of DNA virus infections","volume":"151","author":"Hartley","year":"2006","journal-title":"Arch. Virol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1016\/j.antiviral.2014.10.011","article-title":"Development of a high-content screen for the identification of inhibitors directed against the early steps of the cytomegalovirus infectious cycle","volume":"113","author":"Gardner","year":"2015","journal-title":"Antiviral Res."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1021\/ml400529q","article-title":"Digitoxin Analogues with Improved Anticytomegalovirus Activity","volume":"Volume 5","author":"Cai","year":"2014","journal-title":"ACS Medicinal Chemistry Letters"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1642","DOI":"10.1021\/np050226l","article-title":"Digitoxin inhibits the growth of cancer cell lines at concentrations commonly found in cardiac patients","volume":"68","author":"Pastor","year":"2005","journal-title":"J. Nat. Prod."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"4891","DOI":"10.1128\/AAC.00898-12","article-title":"Human cytomegalovirus inhibition by cardiac glycosides: Evidence for involvement of the HERG gene","volume":"56","author":"Kapoor","year":"2012","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1146\/annurev.biochem.71.102201.141218","article-title":"Biochemistry of Na,K-ATPase","volume":"71","author":"Kaplan","year":"2002","journal-title":"Annu. Rev. Biochem."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Clausen, M.V., Hilbers, F., and Poulsen, H. (2017). The Structure and Function of the Na,K-ATPase Isoforms in Health and Disease. Front. Physiol., 8.","DOI":"10.3389\/fphys.2017.00371"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"828","DOI":"10.1093\/brain\/awl340","article-title":"The phenotypic spectrum of rapid-onset dystonia-parkinsonism (RDP) and mutations in the ATP1A3 gene","volume":"130","author":"Brashear","year":"2007","journal-title":"Brain"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1030","DOI":"10.1038\/ng.2358","article-title":"De novo mutations in ATP1A3 cause alternating hemiplegia of childhood","volume":"44","author":"Heinzen","year":"2012","journal-title":"Nat. Genet."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"422","DOI":"10.1111\/epi.12914","article-title":"Novel mutations in ATP1A3 associated with catastrophic early life epilepsy, episodic prolonged apnea, and postnatal microcephaly","volume":"56","author":"Paciorkowski","year":"2015","journal-title":"Epilepsia"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1016\/0304-4157(89)90019-1","article-title":"Isozymes of the Na+\/K+-ATPase","volume":"988","author":"Sweadner","year":"1989","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"2292","DOI":"10.1016\/j.molimm.2006.11.009","article-title":"Oleandrin induces apoptosis in human, but not in murine cells: Dephosphorylation of Akt, expression of FasL, and alteration of membrane fluidity","volume":"44","author":"Raghavendra","year":"2007","journal-title":"Mol. Immunol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"114","DOI":"10.2174\/156802608783378828","article-title":"The de novo synthesis of oligosaccharides: Application to the medicinal chemistry SAR-study of digitoxin","volume":"8","author":"Zhou","year":"2008","journal-title":"Curr. Top. Med. Chem."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1021\/ml100290d","article-title":"Synthesis and Evaluation of the alpha-D-\/alpha-L-Rhamnosyl and Amicetosyl Digitoxigenin Oligomers as Anti-tumor Agents","volume":"2","author":"Wang","year":"2011","journal-title":"ACS Med. Chem. Lett."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1186\/1743-422X-8-40","article-title":"Recombinant Luciferase-Expressing Human Cytomegalovirus (CMV) for evaluation of CMV inhibitors","volume":"8","author":"He","year":"2011","journal-title":"Virol. J."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1016\/S0166-0934(02)00265-3","article-title":"Quantitative-competitive PCR monitoring of viral load following experimental guinea pig cytomegalovirus infection","volume":"108","author":"Schleiss","year":"2003","journal-title":"J. Virol. Methods"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"635","DOI":"10.1099\/jgv.0.001419","article-title":"Human cytomegalovirus major immediate early transcripts arise predominantly from the canonical major immediate early promoter in reactivating progenitor-derived dendritic cells","volume":"101","author":"Mason","year":"2020","journal-title":"J. Gen. Virol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"17492","DOI":"10.1073\/pnas.1900783116","article-title":"Alternative promoters drive human cytomegalovirus reactivation from latency","volume":"116","author":"Rak","year":"2019","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"D442","DOI":"10.1093\/nar\/gkad1058","article-title":"ELM-the Eukaryotic Linear Motif resource-2024 update","volume":"52","author":"Kumar","year":"2024","journal-title":"Nucleic Acids Res."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Nguyen Ba, A.N., Pogoutse, A., Provart, N., and Moses, A.M. (2009). NLStradamus: A simple Hidden Markov Model for nuclear localization signal prediction. BMC Bioinform., 10.","DOI":"10.1186\/1471-2105-10-202"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"C723","DOI":"10.1152\/ajpcell.00462.2010","article-title":"A practical guide to evaluating colocalization in biological microscopy","volume":"300","author":"Dunn","year":"2011","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1111\/j.1365-2818.2006.01706.x","article-title":"A guided tour into subcellular colocalization analysis in light microscopy","volume":"224","author":"Bolte","year":"2006","journal-title":"J. Microsc."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"6299","DOI":"10.1038\/onc.2008.305","article-title":"Regulation of apoptosis by PML and the PML-NBs","volume":"27","author":"Bernardi","year":"2008","journal-title":"Oncogene"},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Cheng, X., and Kao, H.Y. (2012). Post-translational modifications of PML: Consequences and implications. Front. Oncol., 2.","DOI":"10.3389\/fonc.2012.00210"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"5850","DOI":"10.1128\/JVI.01979-15","article-title":"Emerging Role of PML Nuclear Bodies in Innate Immune Signaling","volume":"90","author":"Scherer","year":"2016","journal-title":"J. Virol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1016\/j.cytogfr.2014.04.008","article-title":"PML control of cytokine signaling","volume":"25","author":"Maarifi","year":"2014","journal-title":"Cytokine Growth Factor. Rev."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1660","DOI":"10.1128\/MCB.01478-14","article-title":"Promyelocytic Leukemia Protein Isoform II Promotes Transcription Factor Recruitment to Activate Interferon Beta and Interferon-Responsive Gene Expression","volume":"35","author":"Chen","year":"2015","journal-title":"Mol. Cell Biol."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Kim, Y.E., and Ahn, J.H. (2015). Positive role of promyelocytic leukemia protein in type I interferon response and its regulation by human cytomegalovirus. PLoS Pathog., 11.","DOI":"10.1371\/journal.ppat.1004785"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1016\/S0014-5793(04)00292-3","article-title":"Up-regulation of Na(+),K(+)-ATPase alpha 3-isoform and down-regulation of the alpha1-isoform in human colorectal cancer","volume":"563","author":"Sakai","year":"2004","journal-title":"FEBS Lett."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"2319","DOI":"10.1158\/1535-7163.MCT-08-1085","article-title":"Oleandrin-mediated inhibition of human tumor cell proliferation: Importance of Na,K-ATPase alpha subunits as drug targets","volume":"8","author":"Yang","year":"2009","journal-title":"Mol. Cancer Ther."},{"key":"ref_44","first-page":"271","article-title":"Human tumor cell sensitivity to oleandrin is dependent on relative expression of Na+, K+ -ATPase subunitst","volume":"8","author":"Lin","year":"2010","journal-title":"J. Exp. Ther. Oncol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1006\/abbi.1994.1136","article-title":"Ouabain binding kinetics of the rat alpha two and alpha three isoforms of the sodium-potassium adenosine triphosphate","volume":"310","author":"Lingrel","year":"1994","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"19582","DOI":"10.1074\/jbc.M110.119248","article-title":"Selectivity of digitalis glycosides for isoforms of human Na,K-ATPase","volume":"285","author":"Katz","year":"2010","journal-title":"J. Biol. Chem."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1002\/mc.21968","article-title":"Cellular location and expression of Na+, K+ -ATPase alpha subunits affect the anti-proliferative activity of oleandrin","volume":"53","author":"Yang","year":"2014","journal-title":"Mol. Carcinog."},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Milutinovic, S., Heynen-Genel, S., Chao, E., Dewing, A., Solano, R., Milan, L., Barron, N., He, M., Diaz, P.W., and Matsuzawa, S. (2016). Cardiac Glycosides Activate the Tumor Suppressor and Viral Restriction Factor Promyelocytic Leukemia Protein (PML). PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0152692"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"2819","DOI":"10.1038\/sj.onc.1207533","article-title":"PML nuclear bodies and apoptosis","volume":"23","author":"Takahashi","year":"2004","journal-title":"Oncogene"},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Ivanschitz, L., De The, H., and Le Bras, M. (2013). PML, SUMOylation, and Senescence. Front. Oncol., 3.","DOI":"10.3389\/fonc.2013.00171"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"249","DOI":"10.4161\/cc.26988","article-title":"Dynamics of histone H3.3 deposition in proliferating and senescent cells reveals a DAXX-dependent targeting to PML-NBs important for pericentromeric heterochromatin organization","volume":"13","author":"Corpet","year":"2014","journal-title":"Cell Cycle"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"3473","DOI":"10.1128\/MCB.24.8.3473-3484.2004","article-title":"Repression of PML nuclear body-associated transcription by oxidative stress-activated Bach2","volume":"24","author":"Tashiro","year":"2004","journal-title":"Mol. Cell Biol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1016\/S1047-8477(02)00571-3","article-title":"Cell cycle-dependent association of PML bodies with sites of active transcription in nuclei of mammalian cells","volume":"140","author":"Kiesslich","year":"2002","journal-title":"J. Struct. Biol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"2518","DOI":"10.1242\/jcs.02965","article-title":"PML nuclear bodies are highly organised DNA-protein structures with a function in heterochromatin remodelling at the G2 phase","volume":"119","author":"Luciani","year":"2006","journal-title":"J. Cell Sci."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1026","DOI":"10.1242\/jcs.02816","article-title":"The number of PML nuclear bodies increases in early S phase by a fission mechanism","volume":"119","author":"Dellaire","year":"2006","journal-title":"J. Cell Sci."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1034","DOI":"10.1242\/jcs.02817","article-title":"Mitotic accumulations of PML protein contribute to the re-establishment of PML nuclear bodies in G1","volume":"119","author":"Dellaire","year":"2006","journal-title":"J. Cell Sci."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"819","DOI":"10.1016\/j.biochi.2007.01.004","article-title":"PML and PML nuclear bodies: Implications in antiviral defence","volume":"89","author":"Everett","year":"2007","journal-title":"Biochimie"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1002\/path.4426","article-title":"PML nuclear bodies: Regulation, function and therapeutic perspectives","volume":"234","author":"Sahin","year":"2014","journal-title":"J. Pathol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1007\/978-3-319-53168-7_4","article-title":"The Human CMV IE1 Protein: An Offender of PML Nuclear Bodies","volume":"223","author":"Scherer","year":"2017","journal-title":"Adv. Anat. Embryol. Cell Biol."},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Nisole, S., Maroui, M.A., Mascle, X.H., Aubry, M., and Chelbi-Alix, M.K. (2013). Differential Roles of PML Isoforms. Front. Oncol., 3.","DOI":"10.3389\/fonc.2013.00125"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1128\/JVI.02049-16","article-title":"The Human Cytomegalovirus IE1 Protein Antagonizes PML Nuclear Body-Mediated Intrinsic Immunity via the Inhibition of PML De Novo SUMOylation","volume":"91","author":"Schilling","year":"2017","journal-title":"J. Virol."},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Paulus, C., Harwardt, T., Walter, B., Marxreiter, A., Zenger, M., Reuschel, E., and Nevels, M.M. (2020). Revisiting promyelocytic leukemia protein targeting by human cytomegalovirus immediate-early protein 1. PLoS Pathog., 16.","DOI":"10.1371\/journal.ppat.1008537"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1042\/BJ20041294","article-title":"The expression of the human neuronal alpha3 Na+,K+-ATPase subunit gene is regulated by the activity of the Sp1 and NF-Y transcription factors","volume":"386","author":"Benfante","year":"2005","journal-title":"Biochem. J."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"4638","DOI":"10.1128\/jvi.71.6.4638-4648.1997","article-title":"Induction of the transcription factor Sp1 during human cytomegalovirus infection mediates upregulation of the p65 and p105\/p50 NF-kappaB promoters","volume":"71","author":"Yurochko","year":"1997","journal-title":"J. Virol."},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Karas, K., Salkowska, A., Dastych, J., Bachorz, R.A., and Ratajewski, M. (2020). Cardiac glycosides with target at direct and indirect interactions with nuclear receptors. Biomed. Pharmacother., 127.","DOI":"10.1016\/j.biopha.2020.110106"},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Adamson, C.S., and Nevels, M.M. (2020). Bright and Early: Inhibiting Human Cytomegalovirus by Targeting Major Immediate-Early Gene Expression or Protein Function. Viruses, 12.","DOI":"10.3390\/v12010110"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"9631","DOI":"10.1073\/pnas.0504097102","article-title":"Cardiac glycosides inhibit TNF-alpha\/NF-kappaB signaling by blocking recruitment of TNF receptor-associated death domain to the TNF receptor","volume":"102","author":"Yang","year":"2005","journal-title":"Proc. Natl. Acad. Sci. USA"}],"container-title":["Viruses"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4915\/17\/3\/398\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T16:50:43Z","timestamp":1760028643000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4915\/17\/3\/398"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,3,11]]},"references-count":67,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2025,3]]}},"alternative-id":["v17030398"],"URL":"https:\/\/doi.org\/10.3390\/v17030398","relation":{},"ISSN":["1999-4915"],"issn-type":[{"value":"1999-4915","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,3,11]]}}}