{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T08:18:34Z","timestamp":1790497114665,"version":"4.1.0"},"reference-count":136,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2020,9,24]],"date-time":"2020-09-24T00:00:00Z","timestamp":1600905600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01CA187718, R21AR074073, R21AI149761, NCI P30 CA016520"],"award-info":[{"award-number":["R01CA187718, R21AR074073, R21AI149761, NCI P30 CA016520"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Polyomavirus infection is widespread in the human population. This family of viruses normally maintains latent infection within the host cell but can cause a range of human pathologies, especially in immunocompromised individuals. Among several known pathogenic human polyomaviruses, JC polyomavirus (JCPyV) has the potential to cause the demyelinating disease progressive multifocal leukoencephalopathy (PML); BK polyomavirus (BKPyV) can cause nephropathy in kidney transplant recipients, and Merkel cell polyomavirus (MCPyV) is associated with a highly aggressive form of skin cancer, Merkel cell carcinoma (MCC). While the mechanisms by which these viruses give rise to the relevant diseases are not well understood, it is clear that the control of gene expression in each polyomavirus plays an important role in determining the infectious tropism of the virus as well as their potential to promote disease progression. In this review, we discuss the mechanisms governing the transcriptional regulation of these pathogenic human polyomaviruses in addition to the best-studied simian vacuolating virus 40 (SV40). We highlight the roles of viral cis-acting DNA elements, encoded proteins and miRNAs that control the viral gene expression. We will also underline the cellular transcription factors and epigenetic modifications that regulate the gene expression of these viruses.<\/jats:p>","DOI":"10.3390\/v12101072","type":"journal-article","created":{"date-parts":[[2020,9,25]],"date-time":"2020-09-25T01:39:33Z","timestamp":1600997973000},"page":"1072","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["Regulation of Polyomavirus Transcription by Viral and Cellular Factors"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9697-3741","authenticated-orcid":false,"given":"June F.","family":"Yang","sequence":"first","affiliation":[{"name":"Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianxin","family":"You","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,9,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/S0065-230X(10)06001-X","article-title":"Update on human polyomaviruses and cancer","volume":"106","author":"Gjoerup","year":"2010","journal-title":"Adv. Cancer Res."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"514","DOI":"10.1099\/vir.0.047902-0","article-title":"Effects of tat proteins and tat mutants of different human immunodeficiency virus type 1 clades on glial jc virus early and late gene transcription","volume":"94","author":"Wright","year":"2013","journal-title":"J. Gen. Virol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"841","DOI":"10.1084\/jem.20072097","article-title":"Polyomavirus bk with rearranged noncoding control region emerge in vivo in renal transplant patients and increase viral replication and cytopathology","volume":"205","author":"Gosert","year":"2008","journal-title":"J. Exp. Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1096","DOI":"10.1126\/science.1152586","article-title":"Clonal integration of a polyomavirus in human merkel cell carcinoma","volume":"319","author":"Feng","year":"2008","journal-title":"Science"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"10846","DOI":"10.1128\/JVI.00542-09","article-title":"Regulation of gene expression in primate polyomaviruses","volume":"83","author":"White","year":"2009","journal-title":"J. Virol."},{"key":"ref_6","unstructured":"Cole, C.N., and Conzen, S.D. (2001). Polyomaviridae: The viruses and their replication. Fields Virology, Lippincott\/The Williams & Wilkins Co.. [4th ed.]."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"12744","DOI":"10.1073\/pnas.1303526110","article-title":"Identification of an overprinting gene in merkel cell polyomavirus provides evolutionary insight into the birth of viral genes","volume":"110","author":"Carter","year":"2013","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"16272","DOI":"10.1073\/pnas.0806526105","article-title":"T antigen mutations are a human tumor-specific signature for merkel cell polyomavirus","volume":"105","author":"Shuda","year":"2008","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1016\/j.virol.2008.11.001","article-title":"Merkel cell polyomavirus encodes a microrna with the ability to autoregulate viral gene expression","volume":"383","author":"Seo","year":"2009","journal-title":"Virology"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"775","DOI":"10.1016\/j.chom.2016.04.024","article-title":"Identifying the target cells and mechanisms of merkel cell polyomavirus infection","volume":"19","author":"Liu","year":"2016","journal-title":"Cell Host Microbe"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"3695","DOI":"10.1073\/pnas.84.11.3695","article-title":"Regulation of the host range of human papovavirus jcv","volume":"84","author":"Feigenbaum","year":"1987","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1176","DOI":"10.1128\/jvi.66.2.1176-1182.1992","article-title":"Jc virus and simian virus 40 enhancers and transforming proteins: Role in determining tissue specificity and pathogenicity in transgenic mice","volume":"66","author":"Feigenbaum","year":"1992","journal-title":"J. Virol."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Liu, W., Krump, N.A., MacDonald, M., and You, J. (2018). Merkel cell polyomavirus infection of animal dermal fibroblasts. J. Virol., 92.","DOI":"10.1128\/JVI.01610-17"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1597","DOI":"10.1099\/jgv.0.000487","article-title":"Transcription enhancers as major determinants of sv40 polyomavirus growth efficiency and host cell tropism","volume":"97","author":"Schmidt","year":"2016","journal-title":"J. Gen. Virol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"7632","DOI":"10.1073\/pnas.85.20.7632","article-title":"Extinction of jc virus tumor-antigen expression in glial cell--fibroblast hybrids","volume":"85","author":"Beggs","year":"1988","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_16","first-page":"4578","article-title":"The adenine-thymine domain of the simian virus 40 core origin directs DNA bending and coordinately regulates DNA replication","volume":"6","author":"Deb","year":"1986","journal-title":"Mol. Cell Biol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"12118","DOI":"10.1128\/JVI.01336-09","article-title":"The minimum replication origin of merkel cell polyomavirus has a unique large t-antigen loading architecture and requires small t-antigen expression for optimal replication","volume":"83","author":"Kwun","year":"2009","journal-title":"J. Virol."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"L\u2019Honneur, A.S., Leh, H., Laurent-Tchenio, F., Hazan, U., Rozenberg, F., and Bury-Mon\u00e9, S. (2018). Exploring the role of nccr variation on jc polyomavirus expression from dual reporter minicircles. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0199171"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"3864","DOI":"10.1128\/jvi.64.8.3864-3871.1990","article-title":"At least two types of control regions can be found among naturally occurring bk virus strains","volume":"64","author":"Sundsfjord","year":"1990","journal-title":"J. Virol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"3388","DOI":"10.1128\/jvi.62.9.3388-3398.1988","article-title":"Binding of cellular proteins to the regulatory region of bk virus DNA","volume":"62","author":"Markowitz","year":"1988","journal-title":"J. Virol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1086\/314830","article-title":"Bk and jc viruses in patients with systemic lupus erythematosus: Prevalent and persistent bk viruria, sequence stability of the viral regulatory regions, and nondetectable viremia","volume":"180","author":"Sundsfjord","year":"1999","journal-title":"J. Infect. Dis."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"304","DOI":"10.1038\/290304a0","article-title":"In vivo sequence requirements of the sv40 early promotor region","volume":"290","author":"Benoist","year":"1981","journal-title":"Nature"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"2447","DOI":"10.1093\/nar\/11.8.2447","article-title":"The repeated gc-rich motifs upstream from the tata box are important elements of the sv40 early promoter","volume":"11","author":"Everett","year":"1983","journal-title":"Nucleic Acids Res."},{"key":"ref_24","first-page":"1900","article-title":"Complex regulation of simian virus 40 early-region transcription from different overlapping promoters","volume":"4","author":"Buchman","year":"1984","journal-title":"Mol. Cell. Biol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"3139","DOI":"10.1128\/jvi.64.6.3139-3143.1990","article-title":"Isolation of a possible archetypal jc virus DNA sequence from nonimmunocompromised individuals","volume":"64","author":"Yogo","year":"1990","journal-title":"J. Virol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1337","DOI":"10.1126\/science.6095453","article-title":"Jc virus enhancer-promoter active in human brain cells","volume":"226","author":"Kenney","year":"1984","journal-title":"Science"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"498","DOI":"10.1080\/13550280390218887","article-title":"Analysis of the excreted jc virus strains and their potential oral transmission","volume":"9","author":"Major","year":"2003","journal-title":"J. Neurovirol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1016\/S0923-2516(98)80034-4","article-title":"Rearrangements of archetypal regulatory regions in jc virus genomes from urine","volume":"149","author":"Agostini","year":"1998","journal-title":"Res. Virol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1499","DOI":"10.1099\/0022-1317-74-8-1499","article-title":"Human polyomavirus jc promoter\/enhancer rearrangement patterns from progressive multifocal leukoencephalopathy brain are unique derivatives of a single archetypal structure","volume":"74 Pt 8","author":"Ault","year":"1993","journal-title":"J. Gen. Virol."},{"key":"ref_30","first-page":"61","article-title":"Naturally occurring and passage-induced variation in the genome of jc virus","volume":"105","author":"Grinnell","year":"1983","journal-title":"Prog. Clin. Biol. Res."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Henriksen, S., Mittelholzer, C., Gosert, R., Hirsch, H.H., and Rinaldo, C.H. (2015). Human bk polyomavirus plasmid pbkv (34-2) (dunlop) contains mutations not found in the originally published sequences. Genome Announc., 3.","DOI":"10.1128\/genomeA.00046-15"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1016\/0042-6822(87)90252-2","article-title":"Analysis of the early regulatory region of the human papovavirus bk","volume":"158","author":"Deyerle","year":"1987","journal-title":"Virology"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"963","DOI":"10.1016\/0092-8674(79)90209-5","article-title":"The genome of human papovavirus bkv","volume":"18","author":"Seif","year":"1979","journal-title":"Cell"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"743","DOI":"10.1046\/j.1523-1755.2003.00132.x","article-title":"Viral regulatory region sequence variations in kidney tissue obtained from patients with bk virus nephropathy","volume":"64","author":"Randhawa","year":"2003","journal-title":"Kidney Int."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1747","DOI":"10.1128\/jvi.61.5.1747-1750.1987","article-title":"Structure and function of the transcriptional control region of nonpassaged bk virus","volume":"61","author":"Rubinstein","year":"1987","journal-title":"J. Virol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1959","DOI":"10.1002\/jmv.21605","article-title":"Functional analysis of polyomavirus bk non-coding control region quasispecies from kidney transplant recipients","volume":"81","author":"Olsen","year":"2009","journal-title":"J. Med. Virol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1600","DOI":"10.1128\/jvi.65.3.1600-1604.1991","article-title":"Recurring theme of changes in the transcriptional control region of bk virus during adaptation to cell culture","volume":"65","author":"Rubinstein","year":"1991","journal-title":"J. Virol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1449","DOI":"10.1007\/s00705-005-0511-3","article-title":"Human endothelial cells allow passage of an archetypal bk virus (bkv) strain--a tool for cultivation and functional studies of natural bkv strains","volume":"150","author":"Hansen","year":"2005","journal-title":"Arch. Virol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"823","DOI":"10.1128\/jvi.55.3.823-825.1985","article-title":"Decreasing the number of 68-base-pair tandem repeats in the bk virus transcriptional control region reduces plaque size and enhances transforming capacity","volume":"55","author":"Watanabe","year":"1985","journal-title":"J. Virol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"485","DOI":"10.1093\/infdis\/169.3.485","article-title":"Bk and jc viruses in human immunodeficiency virus type 1-infected persons: Prevalence, excretion, viremia, and viral regulatory regions","volume":"169","author":"Sundsfjord","year":"1994","journal-title":"J. Infect. Dis."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"384","DOI":"10.1002\/jmv.20551","article-title":"Genetic variability in bk virus regulatory regions in urine and kidney biopsies from renal-transplant patients","volume":"78","author":"Olsen","year":"2006","journal-title":"J. Med. Virol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"10083","DOI":"10.1128\/JVI.01008-16","article-title":"Imperfect symmetry of sp1 and core promoter sequences regulates early and late virus gene expression of the bidirectional bk polyomavirus noncoding control region","volume":"90","author":"Bethge","year":"2016","journal-title":"J. Virol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"2293","DOI":"10.1099\/vir.0.000181","article-title":"Early and late promoters of bk polyomavirus, merkel cell polyomavirus, trichodysplasia spinulosa-associated polyomavirus and human polyomavirus 12 are among the strongest of all known human polyomaviruses in 10 different cell lines","volume":"96","author":"Moens","year":"2015","journal-title":"J. Gen. Virol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"E4040","DOI":"10.1073\/pnas.1703879114","article-title":"Protein-mediated viral latency is a novel mechanism for merkel cell polyomavirus persistence","volume":"114","author":"Kwun","year":"2017","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1186\/s12985-020-01317-x","article-title":"Promoter activity of merkel cell polyomavirus variants in human dermal fibroblasts and a merkel cell carcinoma cell line","volume":"17","author":"Abdulsalam","year":"2020","journal-title":"Virol. J."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1016\/j.coviro.2016.07.011","article-title":"Merkel cell polyomavirus infection and merkel cell carcinoma","volume":"20","author":"Liu","year":"2016","journal-title":"Curr. Opin. Virol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1687","DOI":"10.1128\/JCM.02348-13","article-title":"Molecular epidemiology of merkel cell polyomavirus: Evidence for geographically related variant genotypes","volume":"52","author":"Filippone","year":"2014","journal-title":"J. Clin. Microbiol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1007\/s11262-013-1023-y","article-title":"Merkel cell polyomavirus (mcpyv) strains in japanese merkel cell carcinomas (mcc) are distinct from caucasian type mcpyvs: Genetic variability and phylogeny of mcpyv genomes obtained from japanese mcpyv-infected mccs","volume":"48","author":"Matsushita","year":"2014","journal-title":"Virus Genes"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.virusres.2016.05.004","article-title":"Phylogenetic and structural analysis of merkel cell polyomavirus vp1 in brazilian samples","volume":"221","author":"Baez","year":"2016","journal-title":"Virus Res."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1601","DOI":"10.1093\/infdis\/jiy070","article-title":"Genetic variability of the noncoding control region of cutaneous merkel cell polyomavirus: Identification of geographically related genotypes","volume":"217","author":"Hashida","year":"2018","journal-title":"J. Infect. Dis."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1016\/0092-8674(84)90231-9","article-title":"Activation of the sv40 late promoter: Direct effects of t antigen in the absence of viral DNA replication","volume":"36","author":"Keller","year":"1984","journal-title":"Cell"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"2040","DOI":"10.1073\/pnas.81.7.2040","article-title":"Stimulation of simian virus 40 late gene expression by simian virus 40 tumor antigen","volume":"81","author":"Brady","year":"1984","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1016\/0092-8674(81)90056-8","article-title":"Sv40 gene expression is modulated by the cooperative binding of t antigen to DNA","volume":"25","author":"Myers","year":"1981","journal-title":"Cell"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1227","DOI":"10.1016\/0092-8674(83)90305-7","article-title":"Sv40 t antigen binding site mutations that affect autoregulation","volume":"32","author":"Rio","year":"1983","journal-title":"Cell"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"847","DOI":"10.1016\/0092-8674(87)90512-5","article-title":"Positive and negative regulation of transcription in vitro: Enhancer-binding protein ap-2 is inhibited by sv40 t antigen","volume":"50","author":"Mitchell","year":"1987","journal-title":"Cell"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/0092-8674(81)90026-X","article-title":"T antigen binding and the control of sv40 gene expression","volume":"26","author":"Tjian","year":"1981","journal-title":"Cell"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1006\/jmbi.1997.1461","article-title":"The sv40 capsid protein vp3 cooperates with the cellular transcription factor sp1 in DNA-binding and in regulating viral promoter activity","volume":"275","author":"Kasamatsu","year":"1998","journal-title":"J. Mol. Biol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"292","DOI":"10.1016\/0042-6822(89)90381-4","article-title":"Regulation of jcvl promoter function: Transactivation of jcvl promoter by jcv and sv40 early proteins","volume":"170","author":"Lashgari","year":"1989","journal-title":"Virology"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"10146","DOI":"10.1128\/JVI.73.12.10146-10157.1999","article-title":"Physical and functional interaction between the y-box binding protein yb-1 and human polyomavirus jc virus large t antigen","volume":"73","author":"Safak","year":"1999","journal-title":"J. Virol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1476","DOI":"10.1128\/JVI.75.3.1476-1486.2001","article-title":"Interaction of jc virus agno protein with t antigen modulates transcription and replication of the viral genome in glial cells","volume":"75","author":"Safak","year":"2001","journal-title":"J. Virol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"288","DOI":"10.1080\/13550280152537111","article-title":"Physical and functional interaction between viral and cellular proteins modulate jcv gene transcription","volume":"7","author":"Safak","year":"2001","journal-title":"J. Neurovirol."},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Ajuh, E.T., Wu, Z., Kraus, E., Weissbach, F.H., Bethge, T., Gosert, R., Fischer, N., and Hirsch, H.H. (2018). Novel human polyomavirus noncoding control regions differ in bidirectional gene expression according to host cell, large t-antigen expression, and clinically occurring rearrangements. J. Virol., 92.","DOI":"10.1128\/JVI.02231-17"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1006\/viro.2000.0351","article-title":"A mutation in the de loop of the vp1 protein that prevents polyomavirus transcription and replication","volume":"272","author":"Garcia","year":"2000","journal-title":"Virology"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"13094","DOI":"10.1128\/JVI.79.20.13094-13104.2005","article-title":"Complete nucleotide sequence of polyomavirus sa12","volume":"79","author":"Cantalupo","year":"2005","journal-title":"J. Virol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1557","DOI":"10.1099\/vir.0.81569-0","article-title":"Activation of early gene transcription in polyomavirus bk by human immunodeficiency virus type 1 tat","volume":"87","author":"Gorrill","year":"2006","journal-title":"J. Gen. Virol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"9823","DOI":"10.1128\/JVI.01144-08","article-title":"Evolutionarily conserved function of a viral microrna","volume":"82","author":"Seo","year":"2008","journal-title":"J. Virol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"682","DOI":"10.1038\/nature03576","article-title":"Sv40-encoded micrornas regulate viral gene expression and reduce susceptibility to cytotoxic t cells","volume":"435","author":"Sullivan","year":"2005","journal-title":"Nature"},{"key":"ref_68","doi-asserted-by":"crossref","unstructured":"Theiss, J.M., Gunther, T., Alawi, M., Neumann, F., Tessmer, U., Fischer, N., and Grundhoff, A. (2015). A comprehensive analysis of replicating merkel cell polyomavirus genomes delineates the viral transcription program and suggests a role for mcv-mir-m1 in episomal persistence. PLoS Pathog., 11.","DOI":"10.1371\/journal.ppat.1004974"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"272","DOI":"10.1016\/j.jcv.2011.08.012","article-title":"Identification and validation of a novel mature microrna encoded by the merkel cell polyomavirus in human merkel cell carcinomas","volume":"52","author":"Lee","year":"2011","journal-title":"J. Clin. Virol. Off. Publ. Pan Am. Soc. Clin. Virol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1303","DOI":"10.1007\/s11481-013-9499-8","article-title":"Clonal immortalized human glial cell lines support varying levels of jc virus infection due to differences in cellular gene expression","volume":"8","author":"Ferenczy","year":"2013","journal-title":"J. Neuroimmune Pharmacol. Off. J. Soc. Neuroimmune Pharmacol."},{"key":"ref_71","doi-asserted-by":"crossref","unstructured":"Wang, X., Li, J., Schowalter, R.M., Jiao, J., Buck, C.B., and You, J. (2012). Bromodomain protein brd4 plays a key role in merkel cell polyomavirus DNA replication. PLoS Pathog., 8.","DOI":"10.1371\/journal.ppat.1003021"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1016\/0092-8674(83)90210-6","article-title":"The promoter-specific transcription factor sp1 binds to upstream sequences in the sv40 early promoter","volume":"35","author":"Dynan","year":"1983","journal-title":"Cell"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1126\/science.2996137","article-title":"Bidirectional sv40 transcription mediated by tandem sp1 binding interactions","volume":"230","author":"Gidoni","year":"1985","journal-title":"Science"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"659","DOI":"10.1101\/gad.4.4.659","article-title":"Sv40 stimulates expression of the transacting factor sp1 at the mrna level","volume":"4","author":"Saffer","year":"1990","journal-title":"Genes Dev."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"669","DOI":"10.1016\/0092-8674(83)90053-3","article-title":"Isolation of transcription factors that discriminate between different promoters recognized by rna polymerase ii","volume":"32","author":"Dynan","year":"1983","journal-title":"Cell"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1038\/332557a0","article-title":"Enhancer binding factors ap-4 and ap-1 act in concert to activate sv40 late transcription in vitro","volume":"332","author":"Mermod","year":"1988","journal-title":"Nature"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1101\/gad.4.2.287","article-title":"Transcription factor lsf binds two variant bipartite sites within the sv40 late promoter","volume":"4","author":"Huang","year":"1990","journal-title":"Genes Dev."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1128\/CMR.05031-11","article-title":"Molecular biology, epidemiology, and pathogenesis of progressive multifocal leukoencephalopathy, the jc virus-induced demyelinating disease of the human brain","volume":"25","author":"Ferenczy","year":"2012","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"4743","DOI":"10.1073\/pnas.90.10.4743","article-title":"Regulation of jc virus by the pou-domain transcription factor tst-1: Implications for progressive multifocal leukoencephalopathy","volume":"90","author":"Wegner","year":"1993","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"5944","DOI":"10.1128\/jvi.70.9.5944-5953.1996","article-title":"Transcriptional regulation of human polyomavirus jc: Evidence for a functional interaction between rela (p65) and the y-box-binding protein, yb-1","volume":"70","author":"Raj","year":"1996","journal-title":"J. Virol."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"665","DOI":"10.1128\/JVI.77.1.665-672.2003","article-title":"Regulation of human polyomavirus jc virus gene transcription by ap-1 in glial cells","volume":"77","author":"Sadowska","year":"2003","journal-title":"J. Virol."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"196","DOI":"10.1186\/s12985-015-0426-x","article-title":"Molecular interplay between t-antigen and splicing factor, arginine\/serine-rich 1 (srsf1) controls jc virus gene expression in glial cells","volume":"12","author":"Craigie","year":"2015","journal-title":"Virol. J."},{"key":"ref_83","doi-asserted-by":"crossref","unstructured":"Sariyer, I.K., Sariyer, R., Otte, J., and Gordon, J. (2016). Pur-alpha induces jcv gene expression and viral replication by suppressing srsf1 in glial cells. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0156819"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"728","DOI":"10.1177\/1947601911424578","article-title":"Extinction of tumor antigen expression by sf2\/asf in jcv-transformed cells","volume":"2","author":"Uleri","year":"2011","journal-title":"Genes Cancer"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1016\/j.virusres.2009.09.005","article-title":"Modulation of jc virus transcription by c\/ebp\u03b2","volume":"146","author":"Romagnoli","year":"2009","journal-title":"Virus Res."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"14204","DOI":"10.1016\/S0021-9258(19)49698-1","article-title":"Adjacent nuclear factor-1 and activator protein binding sites in the enhancer of the neurotropic jc virus. A common characteristic of many brain-specific genes","volume":"267","author":"Amemiya","year":"1992","journal-title":"J. Biol. Chem."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"572","DOI":"10.1128\/jvi.67.1.572-576.1993","article-title":"Human jc virus perfect palindromic nuclear factor 1-binding sequences important for glial cell-specific expression in differentiating embryonal carcinoma cells","volume":"67","author":"Kumar","year":"1993","journal-title":"J. Virol."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1016\/j.virol.2004.06.021","article-title":"Transcriptional activation of jc virus early promoter by phorbol ester and interleukin-1\u03b2: Critical role of nuclear factor-1","volume":"327","author":"Kim","year":"2004","journal-title":"Virology"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"3042","DOI":"10.1099\/vir.0.023184-0","article-title":"Transcription factor spi-b binds unique sequences present in the tandem repeat promoter\/enhancer of jc virus and supports viral activity","volume":"91","author":"Marshall","year":"2010","journal-title":"J. Gen. Virol."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1111\/j.1348-0421.2007.tb03915.x","article-title":"Identification of ddx1 as a jc virus transcriptional control region-binding protein","volume":"51","author":"Sunden","year":"2007","journal-title":"Microbiol. Immunol."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1111\/j.1348-0421.2007.tb03907.x","article-title":"Ddx1 promotes proliferation of the jc virus through transactivation of its promoter","volume":"51","author":"Sunden","year":"2007","journal-title":"Microbiol. Immunol."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"3264","DOI":"10.1128\/JVI.06369-11","article-title":"Stimulation of bk virus DNA replication by nfi family transcription factors","volume":"86","author":"Liang","year":"2012","journal-title":"J. Virol."},{"key":"ref_93","first-page":"323","article-title":"Interaction of human polyomavirus bk with the tumor-suppressor protein p53","volume":"13","author":"Shivakumar","year":"1996","journal-title":"Oncogene"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1006\/viro.2001.1024","article-title":"Nuclear factor 1 family members mediate repression of the bk virus late promoter","volume":"287","author":"Kraus","year":"2001","journal-title":"Virology"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.virol.2005.02.006","article-title":"Cooperative interaction of p65 and c\/ebp\u03b2 modulates transcription of bkv early promoter","volume":"335","author":"Gorrill","year":"2005","journal-title":"Virology"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"1722","DOI":"10.1128\/JVI.01918-09","article-title":"Transcriptional regulation of bk virus by nuclear factor of activated t cells","volume":"84","author":"Jordan","year":"2010","journal-title":"J. Virol."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"3396","DOI":"10.1128\/JVI.03625-14","article-title":"Sp1 sites in the noncoding control region of bk polyomavirus are key regulators of bidirectional viral early and late gene expression","volume":"89","author":"Bethge","year":"2015","journal-title":"J. Virol."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"544","DOI":"10.1038\/323544a0","article-title":"Cell-type specific protein binding to the enhancer of simian virus 40 in nuclear extracts","volume":"323","author":"Davidson","year":"1986","journal-title":"Nature"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1126\/science.7618106","article-title":"Integration of map kinase signal transduction pathways at the serum response element","volume":"269","author":"Whitmarsh","year":"1995","journal-title":"Science"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"1022","DOI":"10.1016\/j.jmb.2007.06.080","article-title":"Histone hyperacetylation during sv40 transcription is regulated by p300 and rna polymerase ii translocation","volume":"371","author":"Balakrishnan","year":"2007","journal-title":"J. Mol. Biol."},{"key":"ref_101","doi-asserted-by":"crossref","unstructured":"Schowalter, R.M., and Buck, C.B. (2013). The merkel cell polyomavirus minor capsid protein. PLoS Pathog., 9.","DOI":"10.1371\/journal.ppat.1003558"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"10064","DOI":"10.1128\/JVI.00821-07","article-title":"Polyomavirus small t antigen controls viral chromatin modifications through effects on kinetics of virus growth and cell cycle progression","volume":"81","author":"Dahl","year":"2007","journal-title":"J. Virol."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"8171","DOI":"10.1073\/pnas.85.21.8171","article-title":"Inoculation with bk virus may break immunological tolerance to histone and DNA antigens","volume":"85","author":"Flaegstad","year":"1988","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1038\/nrg.2016.59","article-title":"The molecular hallmarks of epigenetic control","volume":"17","author":"Allis","year":"2016","journal-title":"Nat. Rev. Genet."},{"key":"ref_105","doi-asserted-by":"crossref","unstructured":"Balakrishnan, L., and Milavetz, B. (2017). Epigenetic regulation of viral biological processes. Viruses, 9.","DOI":"10.3390\/v9110346"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/S0378-1119(01)00721-1","article-title":"Epigenetics: Interaction of DNA methylation and chromatin","volume":"278","author":"Nakao","year":"2001","journal-title":"Gene"},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"324","DOI":"10.1016\/j.virol.2003.11.010","article-title":"Hyperacetylation and differential deacetylation of histones h4 and h3 define two distinct classes of acetylated sv40 chromosomes early in infection","volume":"319","author":"Milavetz","year":"2004","journal-title":"Virology"},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"528","DOI":"10.4161\/epi.20057","article-title":"Virion-mediated transfer of sv40 epigenetic information","volume":"7","author":"Milavetz","year":"2012","journal-title":"Epigenetics"},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1186\/1743-422X-10-264","article-title":"Epigenetic regulation of polyomavirus jc","volume":"10","author":"Wollebo","year":"2013","journal-title":"Virol. J."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"3394","DOI":"10.1128\/JVI.77.6.3394-3401.2003","article-title":"Glial cell-specific regulation of the jc virus early promoter by histone deacetylase inhibitors","volume":"77","author":"Kim","year":"2003","journal-title":"J. Virol."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.virol.2015.04.009","article-title":"Global profiling of histone modifications in the polyomavirus bk virion minichromosome","volume":"483","author":"Fang","year":"2015","journal-title":"Virology"},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1016\/j.virol.2016.12.023","article-title":"Nucleosome positioning in the regulatory region of sv40 chromatin correlates with the activation and repression of early and late transcription during infection","volume":"503","author":"Kumar","year":"2017","journal-title":"Virology"},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"6470","DOI":"10.1073\/pnas.80.21.6470","article-title":"Complete DNA methylation does not prevent polyoma and simian virus 40 virus early gene expression","volume":"80","author":"Graessmann","year":"1983","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"5142","DOI":"10.1073\/pnas.79.17.5142","article-title":"Methylation of simian virus 40 hpa ii site affects late, but not early, viral gene expression","volume":"79","author":"Fradin","year":"1982","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1007\/s11262-011-0627-3","article-title":"Analysis of DNA methylation in human bk virus","volume":"43","author":"Chang","year":"2011","journal-title":"Virus Genes"},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1038\/371435a0","article-title":"Spl elements protect a cpg island from de novo methylation","volume":"371","author":"Brandeis","year":"1994","journal-title":"Nature"},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"2282","DOI":"10.1101\/gad.8.19.2282","article-title":"Sp1 sites in the mouse aprt gene promoter are required to prevent methylation of the cpg island","volume":"8","author":"Macleod","year":"1994","journal-title":"Genes Dev."},{"key":"ref_118","doi-asserted-by":"crossref","unstructured":"Khalili, K., Safak, M., Del Valle, L., and White, M.K. (2008). Jc virus molecular biology and the human demyelinating disease, progressive multifocal leukoencephalopathy. Neurotropic Viral Infections, Cambridge University Press.","DOI":"10.1017\/CBO9780511541728.014"},{"key":"ref_119","doi-asserted-by":"crossref","unstructured":"DuShane, J.K., Wilczek, M.P., Mayberry, C.L., and Maginnis, M.S. (2018). Erk is a critical regulator of jc polyomavirus infection. J. Virol., 92.","DOI":"10.1128\/JVI.01529-17"},{"key":"ref_120","doi-asserted-by":"crossref","unstructured":"DuShane, J.K., Mayberry, C.L., Wilczek, M.P., Nichols, S.L., and Maginnis, M.S. (2019). Jcpyv-induced mapk signaling activates transcription factors during infection. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20194779"},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"4215","DOI":"10.1002\/j.1460-2075.1989.tb08607.x","article-title":"The sv40 tc-ii(kappa b) enhanson binds ubiquitous and cell type specifically inducible nuclear proteins from lymphoid and non-lymphoid cell lines","volume":"8","author":"Macchi","year":"1989","journal-title":"EMBO J."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"1959","DOI":"10.1093\/nar\/21.8.1959","article-title":"The transcriptional enhancer element, kappa b, regulates promoter activity of the human neurotropic virus, jcv, in cells derived from the cns","volume":"21","author":"Ranganathan","year":"1993","journal-title":"Nucleic Acids Res."},{"key":"ref_123","doi-asserted-by":"crossref","unstructured":"White, M.K., Kaminski, R., Khalili, K., and Wollebo, H.S. (2014). Rad51 activates polyomavirus jc early transcription. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0110122"},{"key":"ref_124","doi-asserted-by":"crossref","unstructured":"Cheng, J., Park, D.E., Berrios, C., White, E.A., Arora, R., Yoon, R., Branigan, T., Xiao, T., Westerling, T., and Federation, A. (2017). Merkel cell polyomavirus recruits mycl to the ep400 complex to promote oncogenesis. PLoS Pathog., 13.","DOI":"10.1371\/journal.ppat.1006668"},{"key":"ref_125","doi-asserted-by":"crossref","unstructured":"Jiang, M., Zhao, L., Gamez, M., and Imperiale, M.J. (2012). Roles of atm and atr-mediated DNA damage responses during lytic bk polyomavirus infection. PLoS Pathog., 8.","DOI":"10.1371\/journal.ppat.1002898"},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"3285","DOI":"10.1128\/JVI.03656-13","article-title":"Host DNA damage response factors localize to merkel cell polyomavirus DNA replication sites to support efficient viral DNA replication","volume":"88","author":"Tsang","year":"2014","journal-title":"J. Virol."},{"key":"ref_127","doi-asserted-by":"crossref","unstructured":"De Leo, A., Deng, Z., Vladimirova, O., Chen, H.-S., Dheekollu, J., Calderon, A., Myers, K.A., Hayden, J., Keeney, F., and Kaufer, B.B. (2019). Lana oligomeric architecture is essential for kshv nuclear body formation and viral genome maintenance during latency. PLoS Pathog., 15.","DOI":"10.1371\/journal.ppat.1007489"},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1038\/s41467-017-02089-9","article-title":"Kshv episomes reveal dynamic chromatin loop formation with domain-specific gene regulation","volume":"9","author":"Campbell","year":"2018","journal-title":"Nat. Commun."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"e01413","DOI":"10.1128\/JVI.01413-17","article-title":"The epstein-barr virus episome maneuvers between nuclear chromatin compartments during reactivation","volume":"92","author":"Moquin","year":"2018","journal-title":"J. Virol."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"4268","DOI":"10.1038\/s41467-018-06739-4","article-title":"Tridimensional infiltration of DNA viruses into the host genome shows preferential contact with active chromatin","volume":"9","author":"Moreau","year":"2018","journal-title":"Nat. Commun."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1111\/j.1600-0625.2009.00853.x","article-title":"Molecular pathogenesis of merkel cell carcinoma","volume":"18","author":"Houben","year":"2009","journal-title":"Exp. Dermatol."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1146\/annurev-pathol-011110-130227","article-title":"Merkel cell carcinoma: A virus-induced human cancer","volume":"7","author":"Chang","year":"2012","journal-title":"Annu. Rev. Pathol."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"7064","DOI":"10.1128\/JVI.02400-09","article-title":"Merkel cell polyomavirus-infected merkel cell carcinoma cells require expression of viral t antigens","volume":"84","author":"Houben","year":"2010","journal-title":"J. Virol."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"1479","DOI":"10.1038\/jid.2013.483","article-title":"Merkel cell polyomavirus-positive merkel cell carcinoma requires viral small t-antigen for cell proliferation","volume":"134","author":"Shuda","year":"2014","journal-title":"J. Investig. Dermatol."},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"847","DOI":"10.1002\/ijc.26076","article-title":"An intact retinoblastoma protein-binding site in merkel cell polyomavirus large t antigen is required for promoting growth of merkel cell carcinoma cells","volume":"130","author":"Houben","year":"2012","journal-title":"Int. J. Cancer"},{"key":"ref_136","doi-asserted-by":"crossref","unstructured":"Liu, W., Krump, N.A., Buck, C.B., and You, J. (2019). Merkel cell polyomavirus infection and detection. J. Vis. Exp. JoVE, e58950.","DOI":"10.3791\/58950"}],"container-title":["Viruses"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4915\/12\/10\/1072\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T10:13:26Z","timestamp":1760177606000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4915\/12\/10\/1072"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,9,24]]},"references-count":136,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2020,10]]}},"alternative-id":["v12101072"],"URL":"https:\/\/doi.org\/10.3390\/v12101072","relation":{},"ISSN":["1999-4915"],"issn-type":[{"value":"1999-4915","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,9,24]]}}}