{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T00:35:21Z","timestamp":1792197321632,"version":"4.4.0"},"reference-count":83,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2021,5,28]],"date-time":"2021-05-28T00:00:00Z","timestamp":1622160000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["GI-802\/2"],"award-info":[{"award-number":["GI-802\/2"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Although the oncolytic parvovirus H-1PV has entered clinical trials, predicting therapeutic success remains challenging. We investigated whether the antiviral state in tumor cells determines the parvoviral oncolytic efficacy. The interferon\/interferon-stimulated genes (IFN\/ISG)-circuit and its major configurator, human endogenous retroviruses (HERVs), were evaluated using qRT-PCR, ELISA, Western blot, and RNA-Seq techniques. In pancreatic cancer cell lines, H-1PV caused a late global shutdown of innate immunity, whereby the concomitant inhibition of HERVs and IFN\/ISGs was co-regulatory rather than causative. The growth-inhibitory IC50 doses correlated with the power of suppression but not with absolute ISG levels. Moreover, H-1PV was not sensitive to exogenous IFN despite upregulated antiviral ISGs. Such resistance questioned the biological necessity of the oncotropic ISG-shutdown, which instead might represent a surrogate marker for personalized oncolytic efficacy. The disabled antiviral homeostasis may modify the activity of other viruses, as demonstrated by the reemergence of endogenous AluY-retrotransposons. This way of suppression may compromise the interferogenicity of drugs having gemcitabine-like mechanisms of action. This shortcoming in immunogenic cell death induction is however amendable by immune cells which release IFN in response to H-1PV.<\/jats:p>","DOI":"10.3390\/v13061019","type":"journal-article","created":{"date-parts":[[2021,5,31]],"date-time":"2021-05-31T03:45:29Z","timestamp":1622432729000},"page":"1019","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Human Retrotransposons and the Global Shutdown of Homeostatic Innate Immunity by Oncolytic Parvovirus H-1PV in Pancreatic Cancer"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5406-0402","authenticated-orcid":false,"given":"Matthias","family":"Neulinger-Mu\u00f1oz","sequence":"first","affiliation":[{"name":"Department of Surgery, European Pancreas Center, University Hospital Heidelberg, 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4829-5197","authenticated-orcid":false,"given":"Dominik","family":"Schaack","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, University Hospital Heidelberg, 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Svetlana P.","family":"Grekova","sequence":"additional","affiliation":[{"name":"Department of Surgery, European Pancreas Center, University Hospital Heidelberg, 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2870-0848","authenticated-orcid":false,"given":"Andrea S.","family":"Bauer","sequence":"additional","affiliation":[{"name":"German Cancer Research Center (DKFZ), Division of Functional Genome Analysis, 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9649-0424","authenticated-orcid":false,"given":"Thomas","family":"Giese","sequence":"additional","affiliation":[{"name":"Institute of Immunology and German Center for Infection Research (DZIF), Partner Site Heidelberg, University Hospital Heidelberg, 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriel A.","family":"Salg","sequence":"additional","affiliation":[{"name":"Department of Surgery, European Pancreas Center, University Hospital Heidelberg, 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisa","family":"Espinet","sequence":"additional","affiliation":[{"name":"German Cancer Research Center (DKFZ), Division of Stem Cells and Cancer, 69120 Heidelberg, Germany"},{"name":"HI-STEM\u2014Heidelberg Institute for Stem Cell Technology and Experimental Medicine GmbH, 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara","family":"Leuchs","sequence":"additional","affiliation":[{"name":"German Cancer Research Center (DKFZ), Division of Tumor Virology, 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anette","family":"Heller","sequence":"additional","affiliation":[{"name":"Department of Surgery, European Pancreas Center, University Hospital Heidelberg, 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6124-1228","authenticated-orcid":false,"given":"J\u00fcrg P. F.","family":"N\u00fcesch","sequence":"additional","affiliation":[{"name":"German Cancer Research Center (DKFZ), Division of Virus-Associated Carcinogenesis F170, 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miriam","family":"Schenk","sequence":"additional","affiliation":[{"name":"Department of Surgery, European Pancreas Center, University Hospital Heidelberg, 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Volkmar","sequence":"additional","affiliation":[{"name":"German Cancer Research Center (DKFZ), Division of Molecular Oncology of Gastrointestinal Tumors, 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathalia A.","family":"Giese","sequence":"additional","affiliation":[{"name":"Department of Surgery, European Pancreas Center, University Hospital Heidelberg, 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,5,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2620","DOI":"10.1016\/j.ymthe.2017.08.016","article-title":"Oncolytic H-1 Parvovirus Shows Safety and Signs of Immunogenic Activity in a First Phase I\/IIa Glioblastoma Trial","volume":"25","author":"Geletneky","year":"2017","journal-title":"Mol. Ther. J. Am. Soc. Gene Ther."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Hajda, J., Lehmann, M., Krebs, O., Kieser, M., Geletneky, K., Jager, D., Dahm, M., Huber, B., Schoning, T., and Sedlaczek, O. (2017). A non-controlled, single arm, open label, phase II study of intravenous and intratumoral administration of ParvOryx in patients with metastatic, inoperable pancreatic cancer: ParvOryx02 protocol. BMC Cancer, 17.","DOI":"10.1186\/s12885-017-3604-y"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"e955691","DOI":"10.4161\/21624011.2014.955691","article-title":"Consensus guidelines for the detection of immunogenic cell death","volume":"3","author":"Kepp","year":"2014","journal-title":"Oncoimmunology"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1158\/1078-0432.CCR-08-1088","article-title":"Improvement of Gemcitabine-Based Therapy of Pancreatic Carcinoma by Means of Oncolytic Parvovirus H-1PV","volume":"15","author":"Angelova","year":"2009","journal-title":"Clin. Cancer Res."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"996","DOI":"10.1089\/hum.2005.16.996","article-title":"Parvovirus H-1-induced tumor cell death enhances human immune response in vitro via increased phagocytosis, maturation, and cross-presentation by dendritic cells","volume":"16","author":"Moehler","year":"2005","journal-title":"Hum. Gene Ther."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1280","DOI":"10.4161\/cbt.10.12.13455","article-title":"Immune cells participate in the oncosuppressive activity of parvovirus H-1PV and are activated as a result of their abortive infection with this agent","volume":"10","author":"Grekova","year":"2010","journal-title":"Cancer Biol. Ther."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"3067","DOI":"10.1099\/0022-1317-79-12-3067","article-title":"Induction of apoptosis in vitro and in vivo by H-1 parvovirus infection","volume":"79","author":"Ohshima","year":"1998","journal-title":"J. Gen. Virol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"3965","DOI":"10.1128\/JVI.75.8.3965-3970.2001","article-title":"Propagation of rat parvovirus in thymic lymphoma cell line C58(NT)d and subsequent appearance of a resistant cell clone after lytic infection","volume":"75","author":"Ueno","year":"2001","journal-title":"J. Virol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"5263","DOI":"10.1128\/JVI.03688-13","article-title":"Complementary Induction of Immunogenic Cell Death by Oncolytic Parvovirus H-1PV and Gemcitabine in Pancreatic Cancer","volume":"88","author":"Angelova","year":"2014","journal-title":"J. Virol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"e1278332","DOI":"10.1080\/2162402X.2016.1278332","article-title":"Calreticulin promotes immunity and type I interferon-dependent survival in mice with acute myeloid leukemia","volume":"6","author":"Chen","year":"2017","journal-title":"Oncoimmunology"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"e1288334","DOI":"10.1080\/2162402X.2017.1288334","article-title":"Calreticulin and type I interferon: An unsuspected connection","volume":"6","author":"Galluzzi","year":"2017","journal-title":"Oncoimmunology"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"9966","DOI":"10.1128\/JVI.72.12.9966-9977.1998","article-title":"Replicative functions of minute virus of mice NS1 protein are regulated in vitro by phosphorylation through protein kinase C","volume":"72","author":"Nuesch","year":"1998","journal-title":"J. Virol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"7410","DOI":"10.1128\/JVI.73.9.7410-7420.1999","article-title":"DNA unwinding functions of minute virus of mice NS1 protein are modulated specifically by the lambda isoform of protein kinase C","volume":"73","author":"Dettwiler","year":"1999","journal-title":"J. Virol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"8048","DOI":"10.1128\/JVI.77.14.8048-8060.2003","article-title":"Novel PKCeta is required to activate replicative functions of the major nonstructural protein NS1 of minute virus of mice","volume":"77","author":"Lachmann","year":"2003","journal-title":"J. Virol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"3516","DOI":"10.1158\/1078-0432.CCR-11-2325","article-title":"Molecular pathways: Rodent parvoviruses\u2014Mechanisms of oncolysis and prospects for clinical cancer treatment","volume":"18","author":"Nuesch","year":"2012","journal-title":"Clin. Cancer Res. Off. J. Am. Assoc. Cancer Res."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1146\/annurev-virology-031413-085444","article-title":"Parvoviruses: Small Does Not Mean Simple","volume":"1","author":"Cotmore","year":"2014","journal-title":"Annu. Rev. Virol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1141","DOI":"10.1002\/jgm.940","article-title":"Humoral immune responses against minute virus of mice vectors","volume":"8","author":"Lang","year":"2006","journal-title":"J. Gene Med."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Raykov, Z., Grekova, S.P., Horlein, R., Leuchs, B., Giese, T., Giese, N.A., Rommelaere, J., Zawatzky, R., and Daeffler, L. (2013). TLR-9 contributes to the antiviral innate immune sensing of rodent parvoviruses MVMp and H-1PV by normal human immune cells. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0055086"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1007\/BF00202055","article-title":"Parvoviruses are inefficient in inducing interferon-beta, tumor necrosis factor-alpha, or interleukin-6 in mammalian cells","volume":"181","author":"Schlehofer","year":"1992","journal-title":"Med. Microbiol. Immunol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"4932","DOI":"10.1128\/JVI.03508-13","article-title":"Autonomous parvoviruses neither stimulate nor are inhibited by the type I interferon response in human normal or cancer cells","volume":"88","author":"Paglino","year":"2014","journal-title":"J. Virol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"516","DOI":"10.1128\/JVI.01618-09","article-title":"Activation of an antiviral response in normal but not transformed mouse cells: A new determinant of minute virus of mice oncotropism","volume":"84","author":"Grekova","year":"2010","journal-title":"J. Virol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1016\/j.pan.2015.05.480","article-title":"Stratification of pancreatic tissue samples for molecular studies: RNA-based cellular annotation procedure","volume":"15","author":"Heller","year":"2015","journal-title":"Pancreatol. Off. J. Int. Assoc. Pancreatol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1625","DOI":"10.1053\/j.gastro.2018.08.009","article-title":"Immune Cell and Stromal Signature Associated With Progression-Free Survival of Patients With Resected Pancreatic Ductal Adenocarcinoma","volume":"155","author":"Mahajan","year":"2018","journal-title":"Gastroenterology"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"3422","DOI":"10.1158\/1078-0432.CCR-13-2972","article-title":"Prevailing role of contact guidance in intrastromal T-cell trapping in human pancreatic cancer","volume":"20","author":"Hartmann","year":"2014","journal-title":"Clin. Cancer Res. Off. J. Am. Assoc. Cancer Res."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"4429","DOI":"10.1158\/1078-0432.CCR-17-0162","article-title":"Stratification of Pancreatic Ductal Adenocarcinoma: Combinatorial Genetic, Stromal, and Immunologic Markers","volume":"23","author":"Knudsen","year":"2017","journal-title":"Clin. Cancer Res. Off. J.Am. Assoc. Cancer Res."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1016\/j.virusres.2016.06.004","article-title":"Nonstructural protein (NS1) of human parvovirus B19 stimulates host innate immunity and blunts the exogenous type I interferon signaling in vitro","volume":"222","author":"Wu","year":"2016","journal-title":"Virus Res."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1016\/j.virol.2013.03.020","article-title":"Parvovirus evades interferon-dependent viral control in primary mouse embryonic fibroblasts","volume":"442","author":"Mattei","year":"2013","journal-title":"Virology"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"5043","DOI":"10.1128\/JVI.02188-09","article-title":"Translation control by protein kinase R restricts minute virus of mice infection: Role in parvovirus oncolysis","volume":"84","author":"Ventoso","year":"2010","journal-title":"J. Virol."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Kang, H., Liu, D., Tian, J., Hu, X., Zhang, X., Yin, H., Wu, H., Liu, C., Guo, D., and Li, Z. (2017). Feline Panleucopenia Virus NS2 Suppresses the Host IFN-beta Induction by Disrupting the Interaction between TBK1 and STING. Viruses, 9.","DOI":"10.3390\/v9010023"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1142","DOI":"10.1038\/ni.3558","article-title":"Regulation and function of the cGAS-STING pathway of cytosolic DNA sensing","volume":"17","author":"Chen","year":"2016","journal-title":"Nat. Immunol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"4273","DOI":"10.4049\/jimmunol.1303090","article-title":"Age-enhanced endoplasmic reticulum stress contributes to increased Atg9A inhibition of STING-mediated IFN-beta production during Streptococcus pneumoniae infection","volume":"192","author":"Mitzel","year":"2014","journal-title":"J. Immunol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"115315","DOI":"10.18632\/oncotarget.23258","article-title":"Gemcitabine, a broad-spectrum antiviral drug, suppresses enterovirus infections through innate immunity induced by the inhibition of pyrimidine biosynthesis and nucleotide depletion","volume":"8","author":"Lee","year":"2017","journal-title":"Oncotarget"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1038\/nri3845","article-title":"Type I interferons in anticancer immunity","volume":"15","author":"Zitvogel","year":"2015","journal-title":"Nat. Rev. Immunol."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Shin, H.J., Kim, C., and Cho, S. (2018). Gemcitabine and Nucleos(t)ide Synthesis Inhibitors Are Broad-Spectrum Antiviral Drugs that Activate Innate Immunity. Viruses, 10.","DOI":"10.3390\/v10040211"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"961","DOI":"10.1016\/j.cell.2015.07.056","article-title":"DNA-Demethylating Agents Target Colorectal Cancer Cells by Inducing Viral Mimicry by Endogenous Transcripts","volume":"162","author":"Roulois","year":"2015","journal-title":"Cell"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1016\/j.virol.2012.11.014","article-title":"Resistance of pancreatic cancer cells to oncolytic vesicular stomatitis virus: Role of type I interferon signaling","volume":"436","author":"Shah","year":"2013","journal-title":"Virology"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1097\/01.sla.0000261460.07110.f2","article-title":"Type I interferons in the treatment of pancreatic cancer: Mechanisms of action and role of related receptors","volume":"246","author":"Vitale","year":"2007","journal-title":"Ann. Surg."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"770","DOI":"10.1006\/viro.1993.1654","article-title":"NF kappa B upstream regulatory sequences of the HIV-1 LTR are involved in the inhibition of HIV-1 promoter activity by the NS proteins of autonomous parvoviruses H-1 and MVMp","volume":"197","author":"Faisst","year":"1993","journal-title":"Virology"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1038\/nri.2016.27","article-title":"Immune responses to endogenous retroelements: Taking the bad with the good","volume":"16","author":"Kassiotis","year":"2016","journal-title":"Nat. Rev. Immunol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"512","DOI":"10.1016\/j.celrep.2018.03.042","article-title":"Global Cancer Transcriptome Quantifies Repeat Element Polarization between Immunotherapy Responsive and T Cell Suppressive Classes","volume":"23","author":"Solovyov","year":"2018","journal-title":"Cell Rep."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"2489","DOI":"10.3389\/fmicb.2017.02489","article-title":"Physiological and Pathological Transcriptional Activation of Endogenous Retroelements Assessed by RNA-Sequencing of B Lymphocytes","volume":"8","author":"Attig","year":"2017","journal-title":"Front. Microbiol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1143","DOI":"10.1038\/s41591-018-0116-5","article-title":"Tumor innate immunity primed by specific interferon-stimulated endogenous retroviruses","volume":"24","author":"Canadas","year":"2018","journal-title":"Nat. Med."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"974","DOI":"10.1016\/j.cell.2015.07.011","article-title":"Inhibiting DNA Methylation Causes an Interferon Response in Cancer via dsRNA Including Endogenous Retroviruses","volume":"162","author":"Chiappinelli","year":"2015","journal-title":"Cell"},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Alcazer, V., Bonaventura, P., and Depil, S. (2020). Human Endogenous Retroviruses (HERVs): Shaping the Innate Immune Response in Cancers. Cancers, 12.","DOI":"10.3390\/cancers12030610"},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Rejiba, S., Bigand, C., Parmentier, C., Masmoudi, A., and Hajri, A. (2013). Oncosuppressive suicide gene virotherapy \"PVH1-yCD\/5-FC\" for pancreatic peritoneal carcinomatosis treatment: NFkappaB and Akt\/PI3K involvement. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0070594"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1452","DOI":"10.1097\/MPA.0000000000000673","article-title":"Establishment and Characterization of a Novel Cell Line, ASAN-PaCa, Derived From Human Adenocarcinoma Arising in Intraductal Papillary Mucinous Neoplasm of the Pancreas","volume":"45","author":"Heller","year":"2016","journal-title":"Pancreas"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"326","DOI":"10.1002\/jgm.191","article-title":"Transduction of human MCP-3 by a parvoviral vector induces leukocyte infiltration and reduces growth of human cervical carcinoma cell xenografts","volume":"3","author":"Wetzel","year":"2001","journal-title":"J. Gene Med."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1016\/j.jviromet.2015.11.022","article-title":"Standardized large-scale H-1PV production process with efficient quality and quantity monitoring","volume":"229","author":"Leuchs","year":"2016","journal-title":"J. Virol. Methods"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"3143","DOI":"10.1007\/s00253-016-8071-x","article-title":"A novel scalable, robust downstream process for oncolytic rat parvovirus: Isoelectric point-based elimination of empty particles","volume":"101","author":"Leuchs","year":"2017","journal-title":"Appl. Microbiol. Biotechnol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1389","DOI":"10.1007\/s00262-010-0870-9","article-title":"Immunogenicity of SEREX-identified antigens and disease outcome in pancreatic cancer","volume":"59","author":"Heller","year":"2010","journal-title":"Cancer Immunol. Immunother."},{"key":"ref_51","unstructured":"Andrews, S. (2020, April 23). FastQC: A Quality Control Tool for High Throughput Sequence Data. Available online: http:\/\/www.bioinformatics.babraham.ac.uk\/projects\/fastqc."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1521","DOI":"10.12688\/f1000research.7563.1","article-title":"Differential analyses for RNA-seq: Transcript-level estimates improve gene-level inferences","volume":"4","author":"Soneson","year":"2015","journal-title":"F1000Research"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"550","DOI":"10.1186\/s13059-014-0550-8","article-title":"Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2","volume":"15","author":"Love","year":"2014","journal-title":"Genome Biol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"15545","DOI":"10.1073\/pnas.0506580102","article-title":"Gene set enrichment analysis: A knowledge-based approach for interpreting genome-wide expression profiles","volume":"102","author":"Subramanian","year":"2005","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Jeong, H.H., Yalamanchili, H.K., Guo, C., Shulman, J.M., and Liu, Z. (2018, January 3\u20137). An Ultra-Fast and Scalable Quantification Pipeline for Transposable Elements from Next Generation Sequencing Data. Proceedings of the Pacific Symposium on Biocomputing 2018, Kohala, HI, USA.","DOI":"10.1142\/9789813235533_0016"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1186\/s13100-015-0041-9","article-title":"Repbase Update, a database of repetitive elements in eukaryotic genomes","volume":"6","author":"Bao","year":"2015","journal-title":"Mob. DNA"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"2811","DOI":"10.1093\/bioinformatics\/btu393","article-title":"circlize Implements and enhances circular visualization in R","volume":"30","author":"Gu","year":"2014","journal-title":"Bioinformatics"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"2847","DOI":"10.1093\/bioinformatics\/btw313","article-title":"Complex heatmaps reveal patterns and correlations in multidimensional genomic data","volume":"32","author":"Gu","year":"2016","journal-title":"Bioinformatics"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1016\/j.virol.2004.06.040","article-title":"Increased levels of B1 and B2 SINE transcripts in mouse fibroblast cells due to minute virus of mice infection","volume":"327","author":"Williams","year":"2004","journal-title":"Virology"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"236","DOI":"10.1186\/gb-2011-12-12-236","article-title":"Alu elements: Know the SINEs","volume":"12","author":"Deininger","year":"2011","journal-title":"Genome Biol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1097\/MPA.0b013e3181c0decc","article-title":"Identifying molecular markers for chemosensitivity to gemcitabine in pancreatic cancer: Increased expression of interferon-stimulated gene 15 kd is associated with intrinsic chemoresistance","volume":"39","author":"Ina","year":"2010","journal-title":"Pancreas"},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Pertusati, F., Pileggi, E., Richards, J., Wootton, M., Van Leemputte, T., Persoons, L., De Coster, D., Villanueva, X., Daelemans, D., and Steenackers, H. (2020). Drug repurposing: Phosphate prodrugs of anticancer and antiviral FDA-approved nucleosides as novel antimicrobials. J. Antimicrob. Chemother.","DOI":"10.1093\/jac\/dkaa268"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1931","DOI":"10.1038\/bjc.2013.225","article-title":"Hepatitis B virus reactivation risk varies with different chemotherapy regimens commonly used in solid tumours","volume":"108","author":"Ling","year":"2013","journal-title":"Br. J. Cancer"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1083","DOI":"10.1126\/science.aad5497","article-title":"Regulatory evolution of innate immunity through co-option of endogenous retroviruses","volume":"351","author":"Chuong","year":"2016","journal-title":"Science"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"15618","DOI":"10.1038\/ncomms15618","article-title":"DNA exonuclease Trex1 regulates radiotherapy-induced tumour immunogenicity","volume":"8","author":"Alard","year":"2017","journal-title":"Nat. Commun."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1301","DOI":"10.1038\/nm.3708","article-title":"Cancer cell-autonomous contribution of type I interferon signaling to the efficacy of chemotherapy","volume":"20","author":"Sistigu","year":"2014","journal-title":"Nature Med."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"17017","DOI":"10.1038\/cddiscovery.2017.17","article-title":"Reestablishment of p53\/Arf and interferon-beta pathways mediated by a novel adenoviral vector potentiates antiviral response and immunogenic cell death","volume":"3","author":"Hunger","year":"2017","journal-title":"Cell Death Discov."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"e2134","DOI":"10.1038\/cddis.2016.47","article-title":"The oncolytic peptide LTX-315 triggers immunogenic cell death","volume":"7","author":"Zhou","year":"2016","journal-title":"Cell Death Dis."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1016\/j.it.2016.12.004","article-title":"Crosstalk between Cytoplasmic RIG-I and STING Sensing Pathways","volume":"38","author":"Zevini","year":"2017","journal-title":"Trends Immunol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1025","DOI":"10.1038\/ni.3267","article-title":"Sequence-specific activation of the DNA sensor cGAS by Y-form DNA structures as found in primary HIV-1 cDNA","volume":"16","author":"Herzner","year":"2015","journal-title":"Nat. Immunol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"394","DOI":"10.1038\/nature23890","article-title":"cGAS senses long and HMGB\/TFAM-bound U-turn DNA by forming protein-DNA ladders","volume":"549","author":"Andreeva","year":"2017","journal-title":"Nature"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"2937","DOI":"10.15252\/embj.201488726","article-title":"Cytosolic RNA:DNA hybrids activate the cGAS-STING axis","volume":"33","author":"Mankan","year":"2014","journal-title":"EMBO J."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"755","DOI":"10.1111\/j.1462-5822.2007.01082.x","article-title":"Parvovirus interference with intracellular signalling: Mechanism of PKCeta activation in MVM-infected A9 fibroblasts","volume":"10","author":"Lachmann","year":"2008","journal-title":"Cell Microbiol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"633","DOI":"10.1016\/j.it.2012.10.005","article-title":"High-mobility group box family of proteins: Ligand and sensor for innate immunity","volume":"33","author":"Yanai","year":"2012","journal-title":"Trends Immunol."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1016\/0042-6822(92)90290-6","article-title":"Parvovirus H-1 P38 promoter requires the trans-activation region (tar), an SP1 site, and a TATA box for full activity","volume":"187","author":"Gu","year":"1992","journal-title":"Virology"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"326","DOI":"10.1006\/viro.1997.8940","article-title":"An Sp1-binding site and TATA element are sufficient to support full transactivation by proximally bound NS1 protein of minute virus of mice","volume":"240","author":"Lorson","year":"1998","journal-title":"Virology"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1038\/nature23465","article-title":"CDK4\/6 inhibition triggers anti-tumour immunity","volume":"548","author":"Goel","year":"2017","journal-title":"Nature"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1016\/j.cell.2017.11.018","article-title":"Intrinsic Immunity Shapes Viral Resistance of Stem Cells","volume":"172","author":"Wu","year":"2018","journal-title":"Cell"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1016\/j.devcel.2018.01.013","article-title":"An Intrinsic Interferon Program Protects Stem Cells from Viral Infection","volume":"44","author":"Haas","year":"2018","journal-title":"Dev. Cell"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"5892","DOI":"10.1158\/1078-0432.CCR-17-0001","article-title":"Downregulation of Human Endogenous Retrovirus Type K (HERV-K) Viral env RNA in Pancreatic Cancer Cells Decreases Cell Proliferation and Tumor Growth","volume":"23","author":"Li","year":"2017","journal-title":"Clinical Cancer Res. Off. J. Am. Assoc. Cancer Res."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1186\/1479-5876-8-10","article-title":"Anti-viral state segregates two molecular phenotypes of pancreatic adenocarcinoma: Potential relevance for adenoviral gene therapy","volume":"8","author":"Monsurro","year":"2010","journal-title":"J. Transl. Med."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"1288","DOI":"10.3181\/00379727-145-37998","article-title":"Erythrocyte association and interferon production by minute virus of mice","volume":"145","author":"Harris","year":"1974","journal-title":"Soc. Exp. Biol. Med."},{"key":"ref_83","doi-asserted-by":"crossref","unstructured":"Bretscher, C., and Marchini, A. (2019). H-1 Parvovirus as a Cancer-Killing Agent: Past, Present, and Future. Viruses, 11.","DOI":"10.3390\/v11060562"}],"container-title":["Viruses"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4915\/13\/6\/1019\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T06:10:01Z","timestamp":1760163001000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4915\/13\/6\/1019"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,5,28]]},"references-count":83,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2021,6]]}},"alternative-id":["v13061019"],"URL":"https:\/\/doi.org\/10.3390\/v13061019","relation":{},"ISSN":["1999-4915"],"issn-type":[{"value":"1999-4915","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,5,28]]}}}