{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T05:49:13Z","timestamp":1790488153362,"version":"4.1.0"},"reference-count":116,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2021,1,26]],"date-time":"2021-01-26T00:00:00Z","timestamp":1611619200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001322","name":"South African Medical Research Council","doi-asserted-by":"publisher","award":["23108"],"award-info":[{"award-number":["23108"]}],"id":[{"id":"10.13039\/501100001322","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Global cancer incidence and mortality are on the rise. Although cancer is fundamentally a non-communicable disease, a large number of cancers are known to have a viral aetiology. A high burden of infectious agents (Human immunodeficiency virus (HIV), human papillomavirus (HPV), hepatitis B virus (HBV)) in certain Sub-Saharan African countries drives the rates of certain cancers. About one-third of all cancers in Africa are attributed to infection. Seven viruses have been identified with carcinogenic characteristics, namely the HPV, HBV, Hepatitis C virus (HCV), Epstein\u2013Barr virus (EBV), Human T cell leukaemia virus 1 (HTLV-1), Kaposi\u2019s Sarcoma Herpesvirus (KSHV), and HIV-1. The cellular splicing machinery is compromised upon infection, and the virus generates splicing variants that promote cell proliferation, suppress signalling pathways, inhibition of tumour suppressors, alter gene expression through epigenetic modification, and mechanisms to evade an immune response, promoting carcinogenesis. A number of these splice variants are specific to virally-induced cancers. Elucidating mechanisms underlying how the virus utilises these splice variants to maintain its latent and lytic phase will provide insights into novel targets for drug discovery. This review will focus on the splicing genomics, epigenetic modifications induced by and current therapeutic strategies against HPV, HBV, HCV, EBV, HTLV-1, KSHV and HIV-1.<\/jats:p>","DOI":"10.3390\/cells10020239","type":"journal-article","created":{"date-parts":[[2021,1,26]],"date-time":"2021-01-26T08:29:16Z","timestamp":1611649756000},"page":"239","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Aberrant Splicing Events and Epigenetics in Viral Oncogenomics: Current Therapeutic Strategies"],"prefix":"10.3390","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8383-2993","authenticated-orcid":false,"given":"Flavia Zita","family":"Francies","sequence":"first","affiliation":[{"name":"SAMRC\/UP Precision Prevention and Novel Drug Targets for HIV-Associated Cancers (PPNDTHAC) Extramural Unit, Pan African Cancer Research Institute (PACRI), University of Pretoria, Hatfield 0028, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8012-3646","authenticated-orcid":false,"given":"Zodwa","family":"Dlamini","sequence":"additional","affiliation":[{"name":"SAMRC\/UP Precision Prevention and Novel Drug Targets for HIV-Associated Cancers (PPNDTHAC) Extramural Unit, Pan African Cancer Research Institute (PACRI), University of Pretoria, Hatfield 0028, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,1,26]]},"reference":[{"key":"ref_1","unstructured":"WHO (2020, September 16). Cancer. Available online: https:\/\/www.who.int\/news-room\/fact-sheets\/detail\/cancer."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1016\/j.chom.2014.02.011","article-title":"Human viral oncogenesis: A cancer hallmarks analysis","volume":"15","author":"Mesri","year":"2014","journal-title":"Cell Host Microbe"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Mui, U.N., Haley, C.T., and Tyring, S.K. (2017). Viral Oncology: Molecular Biology and Pathogenesis. J. Clin. Med., 6.","DOI":"10.3390\/jcm6120111"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1089\/vim.2016.0109","article-title":"Oncogenic Role of Tumor Viruses in Humans","volume":"30","author":"Akram","year":"2017","journal-title":"Viral Immunol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"e180","DOI":"10.1016\/S2214-109X(19)30488-7","article-title":"Global burden of cancer attributable to infections in 2018: A worldwide incidence analysis","volume":"8","author":"Georges","year":"2020","journal-title":"Lancet Glob. Health"},{"key":"ref_6","unstructured":"IARC (2020, August 04). Biological Agents. Volume 100B: A Review of Human Carcinogens. Available online: https:\/\/monographs.iarc.fr\/wp-content\/uploads\/2018\/06\/mono100B.pdf."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1007\/s13148-011-0026-6","article-title":"Epigenetic mechanisms in virus-induced tumorigenesis","volume":"2","author":"Poreba","year":"2011","journal-title":"Clin. Epigenetics"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1007\/s11899-013-0162-5","article-title":"Post-transplant lymphoproliferative disease (PTLD): Risk factors, diagnosis, and current treatment strategies","volume":"8","author":"Nelson","year":"2013","journal-title":"Curr. Hematol. Malig. Rep."},{"key":"ref_9","first-page":"115","article-title":"Viruses and human cancer","volume":"79","author":"Liao","year":"2006","journal-title":"Yale J. Biol. Med."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Dutta, A., and Sharma-Walia, N. (2019). Curbing Lipids: Impacts ON Cancer and Viral Infection. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20030644"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Yu, X., and Ye, F. (2020). Role of Angiopoietins in Development of Cancer and Neoplasia Associated with Viral Infection. Cells, 9.","DOI":"10.3390\/cells9020457"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1029","DOI":"10.1056\/NEJMra1615896","article-title":"HIV-Associated Cancers and Related Diseases","volume":"378","author":"Yarchoan","year":"2018","journal-title":"N. Engl. J. Med."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"2089","DOI":"10.1002\/ijc.32538","article-title":"Cancer in Africa 2018: The role of infections","volume":"146","author":"Parkin","year":"2020","journal-title":"Int. J. Cancer"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"107","DOI":"10.7196\/SAMJ.8858","article-title":"South African National Cancer Registry: Effect of withheld data from private health systems on cancer incidence estimates","volume":"105","author":"Singh","year":"2015","journal-title":"S. Afr. Med. J."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1236","DOI":"10.3389\/fonc.2019.01236","article-title":"Oncoviruses Can Drive Cancer by Rewiring Signaling Pathways Through Interface Mimicry","volume":"9","author":"Tsai","year":"2019","journal-title":"Front. Oncol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1007\/978-94-007-4525-4_13","article-title":"The role of DNA methylation and histone modifications in transcriptional regulation in humans","volume":"61","author":"Miller","year":"2013","journal-title":"Subcell Biochem."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"730","DOI":"10.7150\/ijbs.6.730","article-title":"Viral oncogenes, noncoding RNAs, and RNA splicing in human tumor viruses","volume":"6","author":"Zheng","year":"2010","journal-title":"Int. J. Biol. Sci."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1565","DOI":"10.1016\/j.jmb.2019.03.001","article-title":"RNA Splicing: A New Paradigm in Host\u2013Pathogen Interactions","volume":"431","author":"Chauhan","year":"2019","journal-title":"J. Mol. Biol."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Cerasuolo, A., Buonaguro, L., Buonaguro, F.M., and Tornesello, M.L. (2020). The Role of RNA Splicing Factors in Cancer: Regulation of Viral and Human Gene Expression in Human Papillomavirus-Related Cervical Cancer. Front. Cell Dev. Biol., 8.","DOI":"10.3389\/fcell.2020.00474"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"e1543","DOI":"10.1002\/wrna.1543","article-title":"Viral modulation of cellular RNA alternative splicing: A new key player in virus\u2013host interactions?","volume":"10","author":"Boudreault","year":"2019","journal-title":"Wiley Interdiscip. Rev. RNA"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"I\u00f1iguez, L.P., and Hern\u00e1ndez, G. (2017). The Evolutionary Relationship between Alternative Splicing and Gene Duplication. Front. Genet., 8.","DOI":"10.3389\/fgene.2017.00014"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1097\/CM9.0000000000000542","article-title":"Significance of alternative splicing in cancer cells","volume":"133","author":"Qi","year":"2020","journal-title":"Chin. Med. J."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Belluti, S., Rigillo, G., and Imbriano, C. (2020). Transcription Factors in Cancer: When Alternative Splicing Determines Opposite Cell Fates. Cells, 9.","DOI":"10.3390\/cells9030760"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1016\/j.virusres.2016.11.016","article-title":"Control of human papillomavirus gene expression by alternative splicing","volume":"231","author":"Graham","year":"2017","journal-title":"Virus Res."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"P631","DOI":"10.1016\/j.trecan.2020.04.011","article-title":"RNA Splicing and Cancer","volume":"6","author":"Wang","year":"2020","journal-title":"Trends Cancer"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Morlando, M., and Fatica, A. (2018). Alteration of Epigenetic Regulation by Long Noncoding RNAs in Cancer. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19020570"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/2045-3701-4-45","article-title":"Epigenetic regulation in cancer progression","volume":"4","author":"Baxter","year":"2014","journal-title":"Cell Biosci."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1093\/bfgp\/elx018","article-title":"Epigenetic regulation of gene expression in cancer: Techniques, resources and analysis","volume":"17","author":"Kagohara","year":"2017","journal-title":"Brief. Funct. Genom."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"523","DOI":"10.3892\/or.2013.2913","article-title":"Epigenetic regulation and cancer (Review)","volume":"31","author":"Chen","year":"2014","journal-title":"Oncol. Rep."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1186\/s12943-020-01197-3","article-title":"Epigenetic regulation in human cancer: The potential role of epi-drug in cancer therapy","volume":"19","author":"Lu","year":"2020","journal-title":"Mol. Cancer"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1186\/s12985-020-01308-y","article-title":"Long noncoding RNAs involvement in Epstein-Barr virus infection and tumorigenesis","volume":"17","author":"Zhang","year":"2020","journal-title":"Virol. J."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1505","DOI":"10.1111\/j.1349-7006.2007.00546.x","article-title":"Basic mechanisms of high-risk human papillomavirus-induced carcinogenesis: Roles of E6 and E7 proteins","volume":"98","author":"Kiyono","year":"2007","journal-title":"Cancer Sci."},{"key":"ref_33","unstructured":"IARC (2007). Human Papillomavirus (HPV) Infection. IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. Human Papillomaviruses, IARC."},{"key":"ref_34","first-page":"6242173","article-title":"Characteristic of HPV Integration in the Genome and Transcriptome of Cervical Cancer Tissues","volume":"2018","author":"Li","year":"2018","journal-title":"BioMed Res. Int."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Olmedo-Nieva, L., Mu\u00f1oz-Bello, J.O., Contreras-Paredes, A., and Lizano, M. (2018). The Role of E6 Spliced Isoforms (E6*) in Human Papillomavirus-Induced Carcinogenesis. Viruses, 10.","DOI":"10.3390\/v10010045"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"e63","DOI":"10.1038\/emi.2014.62","article-title":"Oncogenes and RNA splicing of human tumor viruses","volume":"3","author":"Ajiro","year":"2014","journal-title":"Emerg. Microbes Infect."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1007\/s12250-019-00098-0","article-title":"HPV18 Utilizes Two Alternative Branch Sites for E6*I Splicing to Produce E7 Protein","volume":"34","author":"Brant","year":"2019","journal-title":"Virol. Sin."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"5276","DOI":"10.1128\/JVI.03434-14","article-title":"Human Papillomavirus 16 Oncoprotein Expression Is Controlled by the Cellular Splicing Factor SRSF2 (SC35)","volume":"89","author":"McFarlane","year":"2015","journal-title":"J. Virol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"34070","DOI":"10.18632\/oncotarget.15977","article-title":"Comparative analysis of HPV16 gene expression profiles in cervical and in oropharyngeal squamous cell carcinoma","volume":"8","author":"Cerasuolo","year":"2017","journal-title":"Oncotarget"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1276","DOI":"10.1002\/jmv.21496","article-title":"Molecular analysis of HPV 16 E6I\/E6II spliced mRNAs and correlation with the viral physical state and the grade of the cervical lesion","volume":"81","author":"Cricca","year":"2009","journal-title":"J. Med. Virol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1016\/j.virol.2008.12.037","article-title":"Human papillomavirus type 16 E2 and E6 are RNA-binding proteins and inhibit in vitro splicing of pre-mRNAs with suboptimal splice sites","volume":"386","author":"Bodaghi","year":"2009","journal-title":"Virology"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"12599","DOI":"10.1128\/JVI.02029-14","article-title":"Human papillomavirus type 1 E1^E4 protein is a potent inhibitor of the serine-arginine (SR) protein kinase SRPK1 and inhibits phosphorylation of host SR proteins and of the viral transcription and replication regulator E2","volume":"88","author":"Prescott","year":"2014","journal-title":"J. Virol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1099\/jgv.0.001402","article-title":"Human papillomavirus type 16 infection activates the host serine arginine protein kinase 1 (SRPK1)\u2014Splicing factor axis","volume":"101","author":"Mole","year":"2020","journal-title":"J. Gen. Virol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"207","DOI":"10.3389\/fmicb.2019.00207","article-title":"Cell Type Diversity in Hepatitis B Virus RNA Splicing and Its Regulation","volume":"10","author":"Ito","year":"2019","journal-title":"Front. Microbiol."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Tremblay, M.-P., Armero, V.E.S., Allaire, A., Boudreault, S., Martenon-Brodeur, C., Durand, M., Lapointe, E., Thibault, P., Tremblay-L\u00e9tourneau, M., and Perreault, J.-P. (2016). Global profiling of alternative RNA splicing events provides insights into molecular differences between various types of hepatocellular carcinoma. BMC Genom., 17.","DOI":"10.1186\/s12864-016-3029-z"},{"key":"ref_46","first-page":"1","article-title":"Biological and clinical significance of hepatitis B virus RNA splicing: An update","volume":"2","author":"Candotti","year":"2017","journal-title":"Ann. Blood"},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Chen, J.Y., Chen, W.N., Jiao, B.Y., Lin, W.S., Wu, Y.L., Liu, L.L., and Lin, X. (2014). Hepatitis B spliced protein (HBSP) promotes the carcinogenic effects of benzo [alpha] pyrene by interacting with microsomal epoxide hydrolase and enhancing its hydrolysis activity. BMC Cancer, 14.","DOI":"10.1186\/1471-2407-14-282"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1879","DOI":"10.1096\/fj.14-258715","article-title":"Alternative splicing-regulated protein of hepatitis B virus hacks the TNF-\u03b1-stimulated signaling pathways and limits the extent of liver inflammation","volume":"29","author":"Pol","year":"2015","journal-title":"FASEB J."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"687","DOI":"10.1016\/j.jhep.2017.05.025","article-title":"Alternative splicing of hepatitis B virus: A novel virus\/host interaction altering liver immunity","volume":"67","author":"Duriez","year":"2017","journal-title":"J. Hepatol."},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"G\u00f3mez-Moreno, A., and Garaigorta, U. (2017). Hepatitis B Virus and DNA Damage Response: Interactions and Consequences for the Infection. Viruses, 9.","DOI":"10.3390\/v9100304"},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Jin, Y.-J., Byun, S., Han, S., Chamberlin, J., Kim, D., Kim, M.J., and Lee, Y. (2019). Differential alternative splicing regulation among hepatocellular carcinoma with different risk factors. BMC Med. Genom., 12.","DOI":"10.1186\/s12920-019-0635-z"},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Yin, Y., Lan, J.H., Nguyen, D., Valenzuela, N., Takemura, P., Bolon, Y.T., Springer, B., Saito, K., Zheng, Y., and Hague, T. (2016). Application of High-Throughput Next-Generation Sequencing for HLA Typing on Buccal Extracted DNA: Results from over 10,000 Donor Recruitment Samples. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0165810"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"133","DOI":"10.3389\/fendo.2017.00133","article-title":"Alternative RNA Splicing in the Pathogenesis of Liver Disease","volume":"8","author":"Webster","year":"2017","journal-title":"Front. Endocrinol."},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Kukhanova, M.K., Karpenko, I.L., and Ivanov, A.V. (2020). DEAD-box RNA Helicase DDX3: Functional Properties and Development of DDX3 Inhibitors as Antiviral and Anticancer Drugs. Molecules, 25.","DOI":"10.3390\/molecules25041015"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1517","DOI":"10.1111\/j.1742-4658.2009.06894.x","article-title":"Functional interplay between viral and cellular SR proteins in control of post-transcriptional gene regulation","volume":"276","author":"Lai","year":"2009","journal-title":"FEBS J."},{"key":"ref_56","first-page":"883","article-title":"A double-edged function of DDX3, as an oncogene or tumor suppressor, in cancer progression (Review)","volume":"39","author":"He","year":"2018","journal-title":"Oncol. Rep."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"265","DOI":"10.3389\/fonc.2018.00265","article-title":"Epstein\u2013Barr Virus-Associated Malignancies: Roles of Viral Oncoproteins in Carcinogenesis","volume":"8","author":"Malki","year":"2018","journal-title":"Front. Oncol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"e00238-19","DOI":"10.1128\/JVI.00238-19","article-title":"Mechanisms of B-Cell Oncogenesis Induced by Epstein-Barr Virus","volume":"93","author":"Saha","year":"2019","journal-title":"J. Virol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"12503","DOI":"10.1128\/JVI.76.24.12503-12512.2002","article-title":"The Epstein-Barr Virus Immediate-Early Protein BZLF1 Regulates p53 Function through Multiple Mechanisms","volume":"76","author":"Mauser","year":"2002","journal-title":"J. Virol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"7976","DOI":"10.1128\/JVI.00770-12","article-title":"An Epstein-Barr Virus (EBV) mutant with enhanced BZLF1 expression causes lymphomas with abortive lytic EBV infection in a humanized mouse model","volume":"86","author":"Ma","year":"2012","journal-title":"J. Virol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"787","DOI":"10.1158\/2326-6066.CIR-14-0242","article-title":"The Epstein-Barr virus lytic protein BZLF1 as a candidate target antigen for vaccine development","volume":"3","author":"Hartlage","year":"2015","journal-title":"Cancer Immunol. Res."},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Tornesello, M.L., Annunziata, C., Tornesello, A.L., Buonaguro, L., and Buonaguro, F.M. (2018). Human Oncoviruses and p53 Tumor Suppressor Pathway Deregulation at the Origin of Human Cancers. Cancers (Basel), 10.","DOI":"10.3390\/cancers10070213"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"573","DOI":"10.1007\/s00430-018-0570-1","article-title":"Molecular mechanisms of EBV-driven cell cycle progression and oncogenesis","volume":"208","author":"Yin","year":"2019","journal-title":"Med. Microbiol. Immunol."},{"key":"ref_64","first-page":"1105","article-title":"(-)-Epigallocatechin-3-gallate inhibition of Epstein-Barr virus spontaneous lytic infection involves downregulation of latent membrane protein 1","volume":"15","author":"Liu","year":"2018","journal-title":"Exp. Ther. Med."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"4058","DOI":"10.1128\/JVI.02665-06","article-title":"Multiple Roles of Epstein-Barr Virus SM Protein in Lytic Replication","volume":"81","author":"Han","year":"2007","journal-title":"J. Virol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"3690","DOI":"10.1128\/JVI.77.6.3690-3701.2003","article-title":"The Epstein-Barr Virus SM Protein Induces STAT1 and Interferon-Stimulated Gene Expression","volume":"77","author":"Ruvolo","year":"2003","journal-title":"J. Virol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"7180","DOI":"10.1128\/JVI.00344-08","article-title":"Epstein-Barr Virus SM Protein Functions as an Alternative Splicing Factor","volume":"82","author":"Verma","year":"2008","journal-title":"J. Virol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"9748","DOI":"10.1128\/JVI.01122-07","article-title":"Manipulation of the Toll-Like Receptor 7 Signaling Pathway by Epstein-Barr Virus","volume":"81","author":"Martin","year":"2007","journal-title":"J. Virol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"325","DOI":"10.3389\/fimmu.2019.00325","article-title":"Regulating IRFs in IFN Driven Disease","volume":"10","author":"Jefferies","year":"2019","journal-title":"Front. Immunol."},{"key":"ref_70","doi-asserted-by":"crossref","unstructured":"Armero, V.E.S., Tremblay, M.-P., Allaire, A., Boudreault, S., Martenon-Brodeur, C., Duval, C., Durand, M., Lapointe, E., Thibault, P., and Tremblay-L\u00e9tourneau, M. (2017). Transcriptome-wide analysis of alternative RNA splicing events in Epstein-Barr virus-associated gastric carcinomas. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0176880"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1186\/s12985-019-1137-5","article-title":"The Epstein-Barr virus EBNA1 protein modulates the alternative splicing of cellular genes","volume":"16","author":"Boudreault","year":"2019","journal-title":"Virol. J."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1016\/S1473-3099(19)30402-5","article-title":"Association between HTLV-1 infection and adverse health outcomes: A systematic review and meta-analysis of epidemiological studies","volume":"20","author":"Schierhout","year":"2020","journal-title":"Lancet Infect. Dis."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1186\/s12977-019-0487-9","article-title":"Silencers of HTLV-1 and HTLV-2: The pX-encoded latency-maintenance factors","volume":"16","author":"Harrod","year":"2019","journal-title":"Retrovirology"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"247","DOI":"10.3389\/fmicb.2012.00247","article-title":"HBZ and its roles in HTLV-1 oncogenesis","volume":"3","author":"Zhao","year":"2012","journal-title":"Front. Microbiol."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"2615","DOI":"10.3389\/fmicb.2017.02615","article-title":"HTLV-1 HBZ Viral Protein: A Key Player in HTLV-1 Mediated Diseases","volume":"8","author":"Baratella","year":"2017","journal-title":"Front. Microbiol."},{"key":"ref_76","doi-asserted-by":"crossref","unstructured":"Mohanty, S., and Harhaj, E.W. (2020). Mechanisms of Oncogenesis by HTLV-1 Tax. Pathogens, 9.","DOI":"10.3390\/pathogens9070543"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"18999","DOI":"10.3390\/ijms140918999","article-title":"hnRNP A1: The Swiss army knife of gene expression","volume":"14","author":"Paz","year":"2013","journal-title":"Int. J. Mol. Sci."},{"key":"ref_78","doi-asserted-by":"crossref","unstructured":"Nakano, K., and Watanabe, T. (2016). HTLV-1 Rex Tunes the Cellular Environment Favorable for Viral Replication. Viruses, 8.","DOI":"10.3390\/v8030058"},{"key":"ref_79","doi-asserted-by":"crossref","unstructured":"Mart\u00ednez-Jim\u00e9nez, F., Mui\u00f1os, F., Sent\u00eds, I., Deu-Pons, J., Reyes-Salazar, I., Arnedo-Pac, C., Mularoni, L., Pich, O., Bonet, J., and Kranas, H. (2020). A compendium of mutational cancer driver genes. Nat. Rev. Cancer.","DOI":"10.1038\/s41568-020-0290-x"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"15264","DOI":"10.1038\/ncomms15264","article-title":"Cis-perturbation of cancer drivers by the HTLV-1\/BLV proviruses is an early determinant of leukemogenesis","volume":"8","author":"Rosewick","year":"2017","journal-title":"Nat. Commun."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1007\/s12250-019-00114-3","article-title":"Towards Better Understanding of KSHV Life Cycle: From Transcription and Posttranscriptional Regulations to Pathogenesis","volume":"34","author":"Yan","year":"2019","journal-title":"Virol. Sin."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"277","DOI":"10.4161\/15384101.2014.980657","article-title":"KSHV latent protein LANA2 inhibits sumo2 modification of p53","volume":"14","author":"Laura","year":"2015","journal-title":"Cell Cycle"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"7621","DOI":"10.1038\/sj.onc.1203285","article-title":"Twenty years of p53 research: Structural and functional aspects of the p53 protein","volume":"18","author":"May","year":"1999","journal-title":"Oncogene"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"6970","DOI":"10.1093\/nar\/gkr405","article-title":"Differentially regulated splice variants and systems biology analysis of Kaposi\u2019s sarcoma-associated herpesvirus-infected lymphatic endothelial cells","volume":"39","author":"Chang","year":"2011","journal-title":"Nucleic Acids Res."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1530\/ERC-14-0490","article-title":"Highly specific role of the insulin receptor in breast cancer progression","volume":"22","author":"Rostoker","year":"2015","journal-title":"Endocr.-Relat. Cancer"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"806","DOI":"10.7150\/ijbs.6.806","article-title":"SRp20 is a proto-oncogene critical for cell proliferation and tumor induction and maintenance","volume":"6","author":"Jia","year":"2010","journal-title":"Int. J. Biol. Sci."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"356","DOI":"10.1038\/onc.2010.426","article-title":"Knockdown of splicing factor SRp20 causes apoptosis in ovarian cancer cells and its expression is associated with malignancy of epithelial ovarian cancer","volume":"30","author":"He","year":"2011","journal-title":"Oncogene"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"2792","DOI":"10.1128\/JVI.01856-07","article-title":"Kaposi\u2019s sarcoma-associated herpesvirus ORF57 functions as a viral splicing factor and promotes expression of intron-containing viral lytic genes in spliceosome-mediated RNA splicing","volume":"82","author":"Majerciak","year":"2008","journal-title":"J. Virol."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"5553","DOI":"10.1093\/nar\/gkh876","article-title":"Protein kinase CK2 phosphorylation regulates the interaction of Kaposi\u2019s sarcoma-associated herpesvirus regulatory protein ORF57 with its multifunctional partner hnRNP K","volume":"32","author":"Malik","year":"2004","journal-title":"Nucleic Acids Res."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"3809","DOI":"10.1128\/JVI.77.6.3809-3815.2003","article-title":"K-bZIP of Kaposi\u2019s Sarcoma-Associated Herpesvirus\/Human Herpesvirus 8 (KSHV\/HHV-8) Binds KSHV\/HHV-8 Rta and Represses Rta-Mediated Transactivation","volume":"77","author":"Liao","year":"2003","journal-title":"J. Virol."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"1441","DOI":"10.1128\/JVI.77.2.1441-1451.2003","article-title":"Kaposi\u2019s Sarcoma-Associated Herpesvirus K-bZIP Is a Coregulator of K-Rta: Physical Association and Promoter-Dependent Transcriptional Repression","volume":"77","author":"Izumiya","year":"2003","journal-title":"J. Virol."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"e02177-17","DOI":"10.1128\/JVI.02177-17","article-title":"Kaposi\u2019s Sarcoma-Associated Herpesvirus K8 Is an RNA Binding Protein That Regulates Viral DNA Replication in Coordination with a Noncoding RNA","volume":"92","author":"Liu","year":"2018","journal-title":"J. Virol."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"452","DOI":"10.1016\/j.ccell.2016.03.010","article-title":"Long Noncoding RNAs in Cancer Pathways","volume":"29","author":"Schmitt","year":"2016","journal-title":"Cancer Cell"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"e02515-16","DOI":"10.1128\/JVI.02515-16","article-title":"Characterizing HIV-1 Splicing by Using Next-Generation Sequencing","volume":"91","author":"Emery","year":"2017","journal-title":"J. Virol."},{"key":"ref_95","first-page":"63","article-title":"Can the HIV-1 splicing machinery be targeted for drug discovery?","volume":"9","author":"Dlamini","year":"2017","journal-title":"HIV AIDS (Auckl)"},{"key":"ref_96","doi-asserted-by":"crossref","unstructured":"Byun, S., Han, S., Zheng, Y., Planelles, V., and Lee, Y. (2020). The landscape of alternative splicing in HIV-1 infected CD4 T-cells. BMC Med. Genom., 13.","DOI":"10.1186\/s12920-020-0680-7"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"34573","DOI":"10.1038\/srep34573","article-title":"HIV-1 Vpr N-terminal tagging affects alternative splicing of the viral genome","volume":"6","author":"Baeyens","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_98","doi-asserted-by":"crossref","unstructured":"Caputi, M. (2011). The Regulation of HIV-1 mRNA Biogenesis, RNA Processing, IntechOpen.","DOI":"10.5772\/20899"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1016\/j.virol.2018.01.011","article-title":"Behind the scenes of HIV-1 replication: Alternative splicing as the dependency factor on the quiet","volume":"516","author":"Sertznig","year":"2018","journal-title":"Virology"},{"key":"ref_100","first-page":"77","article-title":"Abnormalities in alternative splicing of angiogenesis-related genes and their role in HIV-related cancers","volume":"9","author":"Mthembu","year":"2017","journal-title":"HIV AIDS (Auckl)"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"P268","DOI":"10.1016\/j.tim.2018.11.004","article-title":"Advances in Analyzing Virus-Induced Alterations of Host Cell Splicing","volume":"27","author":"Ashraf","year":"2018","journal-title":"Trends Microbiol."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"6608","DOI":"10.1128\/JVI.00364-15","article-title":"EFTUD2 Is a Novel Innate Immune Regulator Restricting Hepatitis C Virus Infection through the RIG-I\/MDA5 Pathway","volume":"89","author":"Zhu","year":"2015","journal-title":"J. Virol."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1007\/s00281-020-00780-6","article-title":"Epigenetic modulation in chronic hepatitis B virus infection","volume":"42","author":"Dandri","year":"2020","journal-title":"Semin. Immunopathol."},{"key":"ref_104","doi-asserted-by":"crossref","unstructured":"Tsai, K., and Cullen, B.R. (2020). Epigenetic and epitranscriptomic regulation of viral replication. Nat. Rev. Microbiol.","DOI":"10.1038\/s41579-020-0382-3"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1016\/j.mrrev.2016.09.006","article-title":"Human papillomaviruses in epigenetic regulations","volume":"772","author":"Durzynska","year":"2017","journal-title":"Mutat. Res.\/Rev. Mutat. Res."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1186\/s13148-019-0654-9","article-title":"Control of viral infections by epigenetic-targeted therapy","volume":"11","author":"Nehme","year":"2019","journal-title":"Clin. Epigenetics"},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1007\/s00281-020-00787-z","article-title":"Epigenetic control in Kaposi sarcoma-associated herpesvirus infection and associated disease","volume":"42","author":"Grundhoff","year":"2020","journal-title":"Semin. Immunopathol."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"582","DOI":"10.1038\/s12276-020-0429-6","article-title":"Pathogenic diversity of RNA variants and RNA variation-associated factors in cancer development","volume":"52","author":"Yang","year":"2020","journal-title":"Exp. Mol. Med."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"545","DOI":"10.1016\/S2468-1253(19)30119-0","article-title":"A global scientific strategy to cure hepatitis B","volume":"4","author":"Revill","year":"2019","journal-title":"Lancet Gastroenterol. Hepatol."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"3609","DOI":"10.1073\/pnas.1523686113","article-title":"Spironolactone blocks Epstein\u2013Barr virus production by inhibiting EBV SM protein function","volume":"113","author":"Verma","year":"2016","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"13044","DOI":"10.1073\/pnas.2000625117","article-title":"Epstein\u2013Barr virus co-opts TFIIH component XPB to specifically activate essential viral lytic promoters","volume":"117","author":"Verma","year":"2020","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"3396","DOI":"10.1016\/j.ygeno.2020.06.002","article-title":"Identification of prognostic alternative splicing signatures in hepatitis B or\/and C viruses related hepatocellular carcinoma","volume":"112","author":"Cai","year":"2020","journal-title":"Genomics"},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"75","DOI":"10.3960\/jslrt.54.75","article-title":"Tumor Microenvironment and RIG-I Signaling Molecules in Epstein Barr Virus-Positive and -Negative Classical Hodgkin Lymphoma of the Elderly","volume":"54","author":"Satoh","year":"2014","journal-title":"J. Clin. Exp. Hematop."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"e417","DOI":"10.1038\/bcj.2016.26","article-title":"The microenvironment of classical Hodgkin lymphoma: Heterogeneity by Epstein\u2013Barr virus presence and location within the tumor","volume":"6","author":"Wu","year":"2016","journal-title":"Blood Cancer J."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1038\/s41392-020-00233-4","article-title":"Stress proteins: The biological functions in virus infection, present and challenges for target-based antiviral drug development","volume":"5","author":"Wan","year":"2020","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1016\/j.virusres.2008.06.015","article-title":"Role of RNA chaperones in virus replication","volume":"139","author":"Sola","year":"2009","journal-title":"Virus Res."}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/10\/2\/239\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T05:15:37Z","timestamp":1760159737000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/10\/2\/239"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,1,26]]},"references-count":116,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2021,2]]}},"alternative-id":["cells10020239"],"URL":"https:\/\/doi.org\/10.3390\/cells10020239","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,1,26]]}}}