{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T22:19:31Z","timestamp":1789510771367,"version":"build-2803163510"},"reference-count":82,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2024,10,5]],"date-time":"2024-10-05T00:00:00Z","timestamp":1728086400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Research Grant of the University of Turin","award":["RIBD_RILO_22_01"],"award-info":[{"award-number":["RIBD_RILO_22_01"]}]},{"name":"Research Grant of the University of Turin","award":["BERM_CRT_24_01"],"award-info":[{"award-number":["BERM_CRT_24_01"]}]},{"name":"research grant of the CRT bank","award":["RIBD_RILO_22_01"],"award-info":[{"award-number":["RIBD_RILO_22_01"]}]},{"name":"research grant of the CRT bank","award":["BERM_CRT_24_01"],"award-info":[{"award-number":["BERM_CRT_24_01"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Inflammatory bowel disease (IBD) includes patients affected by Crohn\u2019s disease or ulcerative colitis. IBD is thought to be a chronic immune-mediated disease, but its origin remains elusive, and this limits new therapeutic approaches. Human endogenous retroviruses (HERVs) originate from ancestral infections and represent 8% of the human genome. HERVs are no longer infectious, but some retroviral sequences can be activated, and their aberrant expressions have been implicated in inflammatory and autoimmune disorders. HERV transcription is regulated by TRIM28 and SETDB1, which are also directly involved in epigenetic processes and modulation of the immune response. Using a PCR real-time Taqman amplification assay, we assessed, for the first time, the transcription levels of pol genes of HERV-H, -K, and -W families of env genes of syncytin 1 (SYN1), SYN2, and HERV-W, as well as of TRIM28 and SETDB1 in the whole blood of 48 patients with Crohn\u2019s disease (CD), 20 with ulcerative colitis (UC), and in healthy controls (HC) of comparable age. The transcriptional levels of HERV-H-pol (p = 0.0003) and HERV-K-pol (p = 0.001) were significantly higher in IBD patients compared with HC, with no differences between patients with CD and UC. No significant differences were found for the remaining HERVs between IBD patients and HC. The transcript levels of TRIM28 were significantly downregulated in IBD patients (p &lt; 0.001), without differences between CD and UC, while the SETDB1 levels were preserved. The enhanced transcription of HERV-H-pol and HERV-K-pol, as well as the impaired activation of TRIM28, were not influenced by clinical disease activity and type of treatment. The overexpression of HERVs and impaired transcription of TRIM28 in patients affected by CD or UC suggest that they might be the main actors in the pathophysiology of IBD, opening the way to innovative targeted interventions.<\/jats:p>","DOI":"10.3390\/v16101570","type":"journal-article","created":{"date-parts":[[2024,10,7]],"date-time":"2024-10-07T06:23:18Z","timestamp":1728282198000},"page":"1570","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Enhanced Transcription of Human Endogenous Retroviruses and TRIM28 Downregulation in Patients with Inflammatory Bowel Disease"],"prefix":"10.3390","volume":"16","author":[{"given":"Pier-Angelo","family":"Tovo","sequence":"first","affiliation":[{"name":"Department of Public Health and Pediatric Sciences, University of Turin, Piazza Polonia 94, 10126 Turin, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9421-3087","authenticated-orcid":false,"given":"Davide Giuseppe","family":"Ribaldone","sequence":"additional","affiliation":[{"name":"Department of Medical Sciences, Division of Gastroenterology, University of Turin, 10123 Turin, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1273-3178","authenticated-orcid":false,"given":"Ilaria","family":"Galliano","sequence":"additional","affiliation":[{"name":"Pediatric Laboratory, Department of Public Health and Pediatric Sciences, University of Turin, Regina Margherita Children\u2019s Hospital, Piazza Polonia 94, 10126 Turin, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0529-9481","authenticated-orcid":false,"given":"Gian Paolo","family":"Caviglia","sequence":"additional","affiliation":[{"name":"Department of Medical Sciences, Division of Gastroenterology, University of Turin, 10123 Turin, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maddalena","family":"Dini","sequence":"additional","affiliation":[{"name":"Pediatric Laboratory, Department of Public Health and Pediatric Sciences, University of Turin, Regina Margherita Children\u2019s Hospital, Piazza Polonia 94, 10126 Turin, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valentina","family":"Veglio","sequence":"additional","affiliation":[{"name":"Department of Medical Sciences, Division of Gastroenterology, University of Turin, 10123 Turin, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina","family":"Calvi","sequence":"additional","affiliation":[{"name":"Pediatric Laboratory, Department of Public Health and Pediatric Sciences, University of Turin, Regina Margherita Children\u2019s Hospital, Piazza Polonia 94, 10126 Turin, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paola","family":"Montanari","sequence":"additional","affiliation":[{"name":"Pediatric Laboratory, Department of Public Health and Pediatric Sciences, University of Turin, Regina Margherita Children\u2019s Hospital, Piazza Polonia 94, 10126 Turin, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Demis","family":"Pitoni","sequence":"additional","affiliation":[{"name":"Department of Medical Sciences, Division of Gastroenterology, University of Turin, 10123 Turin, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simone","family":"Frara","sequence":"additional","affiliation":[{"name":"Department of Medical Sciences, Division of Gastroenterology, University of Turin, 10123 Turin, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisa","family":"Tribocco","sequence":"additional","affiliation":[{"name":"Department of Medical Sciences, Division of Gastroenterology, University of Turin, 10123 Turin, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anxhela","family":"Poshnjari","sequence":"additional","affiliation":[{"name":"Department of Medical Sciences, Division of Gastroenterology, University of Turin, 10123 Turin, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9291-1332","authenticated-orcid":false,"given":"Massimiliano","family":"Bergallo","sequence":"additional","affiliation":[{"name":"Pediatric Laboratory, Department of Public Health and Pediatric Sciences, University of Turin, Regina Margherita Children\u2019s Hospital, Piazza Polonia 94, 10126 Turin, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,10,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1627","DOI":"10.1016\/S0140-6736(07)60750-8","article-title":"Inflammatory Bowel Disease: Cause and Immunobiology","volume":"369","author":"Baumgart","year":"2007","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1038\/s41577-024-01008-6","article-title":"Strategies for Targeting Cytokines in Inflammatory Bowel Disease","volume":"24","author":"Neurath","year":"2024","journal-title":"Nat. Rev. Immunol."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Jarmakiewicz-Czaja, S., Zieli\u0144ska, M., Sokal, A., and Filip, R. (2022). Genetic and Epigenetic Etiology of Inflammatory Bowel Disease: An Update. Genes, 13.","DOI":"10.1155\/2022\/4344905"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1093\/ecco-jcc\/jjac127","article-title":"Analysis of Systemic Epigenetic Alterations in Inflammatory Bowel Disease: Defining Geographical, Genetic and Immune-Inflammatory Influences on the Circulating Methylome","volume":"17","author":"Kalla","year":"2023","journal-title":"J. Crohns Colitis"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1038\/s41586-024-07501-1","article-title":"A Disease-Associated Gene Desert Directs Macrophage Inflammation through ETS2","volume":"630","author":"Stankey","year":"2024","journal-title":"Nature"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1053\/j.gastro.2023.03.238","article-title":"Defining Interactions Between the Genome, Epigenome, and the Environment in Inflammatory Bowel Disease: Progress and Prospects","volume":"165","author":"Noble","year":"2023","journal-title":"Gastroenterology"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1016\/j.jcmgh.2023.06.001","article-title":"Genome-Wide Methylation Profiling in 229 Patients With Crohn\u2019s Disease Requiring Intestinal Resection: Epigenetic Analysis of the Trial of Prevention of Post-Operative Crohn\u2019s Disease (TOPPIC)","volume":"16","author":"Ventham","year":"2023","journal-title":"Cell Mol. Gastroenterol. Hepatol."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Bastida, G., M\u00ednguez, A., Nos, P., and Moret-Tatay, I. (2023). Immunoepigenetic Regulation of Inflammatory Bowel Disease: Current Insights into Novel Epigenetic Modulations of the Systemic Immune Response. Genes, 14.","DOI":"10.3390\/genes14030554"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Yoo, J.Y., Groer, M., Dutra, S.V.O., Sarkar, A., and McSkimming, D.I. (2020). Gut Microbiota and Immune System Interactions. Microorganisms, 8.","DOI":"10.3390\/microorganisms8101587"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"4053","DOI":"10.3748\/wjg.v28.i30.4053","article-title":"Gut Microbiota, Inflammatory Bowel Disease and Colorectal Cancer","volume":"28","author":"Quaglio","year":"2022","journal-title":"World J. Gastroenterol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1007\/978-1-0716-3366-3_13","article-title":"Delineating the Role of Toll-Like Receptors in Inflammatory Bowel Disease","volume":"2700","author":"Liang","year":"2023","journal-title":"Methods Mol. Biol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1038\/s41579-019-0189-2","article-title":"Origins and Evolutionary Consequences of Ancient Endogenous Retroviruses","volume":"17","author":"Johnson","year":"2019","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"3321","DOI":"10.1128\/JVI.74.7.3321-3329.2000","article-title":"An Envelope Glycoprotein of the Human Endogenous Retrovirus HERV-W Is Expressed in the Human Placenta and Fuses Cells Expressing the Type D Mammalian Retrovirus Receptor","volume":"74","author":"Blond","year":"2000","journal-title":"J. Virol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"13013","DOI":"10.1073\/pnas.2132646100","article-title":"Genomewide Screening for Fusogenic Human Endogenous Retrovirus Envelopes Identifies Syncytin 2, a Gene Conserved on Primate Evolution","volume":"100","author":"Blaise","year":"2003","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"685","DOI":"10.1002\/eji.201948423","article-title":"Syncytin-1\/HERV-W Envelope Is an Early Activation Marker of Leukocytes and Is Upregulated in Multiple Sclerosis Patients","volume":"50","author":"Casanova","year":"2020","journal-title":"Eur. J. Immunol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"734","DOI":"10.1002\/bies.201200056","article-title":"Endogenous Retroviruses in Mammals: An Emerging Picture of How ERVs Modify Expression of Adjacent Genes","volume":"34","author":"Isbel","year":"2012","journal-title":"Bioessays"},{"key":"ref_17","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_18","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1093\/intimm\/dxy016","article-title":"Mechanisms Controlling Nucleic Acid-Sensing Toll-like Receptors","volume":"30","author":"Miyake","year":"2018","journal-title":"Int. Immunol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"e131093","DOI":"10.1172\/jci.insight.131093","article-title":"Human Endogenous Retrovirus HERV-K(HML-2) RNA Causes Neurodegeneration through Toll-like Receptors","volume":"5","author":"Dembny","year":"2020","journal-title":"JCI Insight"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1038\/ni.2872","article-title":"The Enemy within: Endogenous Retroelements and Autoimmune Disease","volume":"15","author":"Volkman","year":"2014","journal-title":"Nat. Immunol."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Perron, H., Dougier-Reynaud, H.-L., Lomparski, C., Popa, I., Firouzi, R., Bertrand, J.-B., Marusic, S., Portoukalian, J., Jouvin-Marche, E., and Villiers, C.L. (2013). Human Endogenous Retrovirus Protein Activates Innate Immunity and Promotes Experimental Allergic Encephalomyelitis in Mice. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0080128"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1080\/08916934.2020.1777281","article-title":"Enhanced Expression of Human Endogenous Retroviruses in New-Onset Type 1 Diabetes: Potential Pathogenetic and Therapeutic Implications","volume":"53","author":"Tovo","year":"2020","journal-title":"Autoimmunity"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"2429","DOI":"10.1007\/s00431-021-04050-x","article-title":"Overexpression of Endogenous Retroviruses in Children with Celiac Disease","volume":"180","author":"Tovo","year":"2021","journal-title":"Eur. J. Pediatr."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Tovo, P.-A., Galliano, I., Parodi, E., Calvi, C., Gambarino, S., Licciardi, F., Dini, M., Montanari, P., Branca, M., and Ramenghi, U. (2023). Children with Chronic Immune Thrombocytopenia Exhibit High Expression of Human Endogenous Retroviruses TRIM28 and SETDB1. Genes, 14.","DOI":"10.3390\/genes14081569"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"3794","DOI":"10.1016\/j.cell.2021.05.020","article-title":"Endogenous Retroviruses Promote Homeostatic and Inflammatory Responses to the Microbiota","volume":"184","author":"Krishnamurthy","year":"2021","journal-title":"Cell"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"2067","DOI":"10.1101\/gad.10.16.2067","article-title":"KAP-1, a Novel Corepressor for the Highly Conserved KRAB Repression Domain","volume":"10","author":"Friedman","year":"1996","journal-title":"Genes Dev."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"919","DOI":"10.1101\/gad.973302","article-title":"SETDB1: A Novel KAP-1-Associated Histone H3, Lysine 9-Specific Methyltransferase That Contributes to HP1-Mediated Silencing of Euchromatic Genes by KRAB Zinc-Finger Proteins","volume":"16","author":"Schultz","year":"2002","journal-title":"Genes Dev."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"386","DOI":"10.1038\/s41586-020-2127-x","article-title":"Gut Stem Cell Necroptosis by Genome Instability Triggers Bowel Inflammation","volume":"580","author":"Wang","year":"2020","journal-title":"Nature"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"485","DOI":"10.1136\/gutjnl-2020-321339","article-title":"SETDB1 Is Required for Intestinal Epithelial Differentiation and the Prevention of Intestinal Inflammation","volume":"70","author":"Peuker","year":"2021","journal-title":"Gut"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"2269","DOI":"10.4049\/jimmunol.1502486","article-title":"A Histone Methyltransferase ESET Is Critical for T Cell Development","volume":"197","author":"Takikita","year":"2016","journal-title":"J. Immunol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"927","DOI":"10.1038\/nature08858","article-title":"Proviral Silencing in Embryonic Stem Cells Requires the Histone Methyltransferase ESET","volume":"464","author":"Matsui","year":"2010","journal-title":"Nature"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1242\/dev.087585","article-title":"De Novo DNA Methylation of Endogenous Retroviruses Is Shaped by KRAB-ZFPs\/KAP1 and ESET","volume":"140","author":"Rowe","year":"2013","journal-title":"Development"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1260","DOI":"10.1101\/gr.172833.114","article-title":"Interplay of TRIM28 and DNA Methylation in Controlling Human Endogenous Retroelements","volume":"24","author":"Turelli","year":"2014","journal-title":"Genome Res."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Groner, A.C., Meylan, S., Ciuffi, A., Zangger, N., Ambrosini, G., D\u00e9nervaud, N., Bucher, P., and Trono, D. (2010). KRAB-Zinc Finger Proteins and KAP1 Can Mediate Long-Range Transcriptional Repression through Heterochromatin Spreading. PLoS Genet., 6.","DOI":"10.1371\/journal.pgen.1000869"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Krischuns, T., G\u00fcnl, F., Henschel, L., Binder, M., Willemsen, J., Schloer, S., Rescher, U., Gerlt, V., Zimmer, G., and Nordhoff, C. (2018). Phosphorylation of TRIM28 Enhances the Expression of IFN-\u03b2 and Proinflammatory Cytokines During HPAIV Infection of Human Lung Epithelial Cells. Front. Immunol., 9.","DOI":"10.3389\/fimmu.2018.02229"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"25839","DOI":"10.1073\/pnas.1901639116","article-title":"Critical Role for TRIM28 and HP1\u03b2\/\u03b3 in the Epigenetic Control of T Cell Metabolic Reprograming and Effector Differentiation","volume":"116","author":"Gehrmann","year":"2019","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Czerwinska, P., Jaworska, A.M., Wlodarczyk, N.A., and Mackiewicz, A.A. (2020). Melanoma Stem Cell-Like Phenotype and Significant Suppression of Immune Response within a Tumor Are Regulated by TRIM28 Protein. Cancers, 12.","DOI":"10.3390\/cancers12102998"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1159\/000494026","article-title":"Human Endogenous Retroviruses: Residues of Ancient Times Are Differentially Expressed in Crohn\u2019s Disease","volume":"3","author":"Klag","year":"2019","journal-title":"Inflamm. Intestig. Dis."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Grandi, N., and Tramontano, E. (2018). Human Endogenous Retroviruses Are Ancient Acquired Elements Still Shaping Innate Immune Responses. Front. Immunol., 9.","DOI":"10.3389\/fimmu.2018.02039"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"7636","DOI":"10.4049\/jimmunol.176.12.7636","article-title":"The Envelope Protein of a Human Endogenous Retrovirus-W Family Activates Innate Immunity through CD14\/TLR4 and Promotes Th1-like Responses","volume":"176","author":"Rolland","year":"2006","journal-title":"J. Immunol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1093\/ecco-jcc\/jjy113","article-title":"ECCO-ESGAR Guideline for Diagnostic Assessment in IBD Part 1: Initial Diagnosis, Monitoring of Known IBD, Detection of Complications","volume":"13","author":"Maaser","year":"2019","journal-title":"J. Crohns Colitis"},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Gambarino, S., Galliano, I., Clemente, A., Calvi, C., Montanari, P., Pau, A., Dini, M., and Bergallo, M. (2024). Characteristics of RNA Stabilizer RNApro for Peripheral Blood Collection. Diagnostics, 14.","DOI":"10.3390\/diagnostics14100971"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1006\/meth.2001.1262","article-title":"Analysis of Relative Gene Expression Data Using Real-Time Quantitative PCR and the 2(-Delta Delta C(T)) Method","volume":"25","author":"Livak","year":"2001","journal-title":"Methods"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1186\/1744-8069-4-51","article-title":"Quantitative Real-Time PCR Detection of TRPV1-4 Gene Expression in Human Leukocytes from Healthy and Hyposensitive Subjects","volume":"4","author":"Spinsanti","year":"2008","journal-title":"Mol. Pain"},{"key":"ref_45","unstructured":"Biosafety and Biosecurity Policy (2024, July 05). National Institutes of Health (NIH)\u2014Office of Science Policy, Available online: https:\/\/osp.od.nih.gov\/policies\/biosafety-and-biosecurity-policy\/."},{"key":"ref_46","unstructured":"(2024, July 07). Laboratory Biosafety Guidance Related to Coronavirus Disease (COVID-19): Interim Guidance. Available online: https:\/\/www.who.int\/publications\/i\/item\/WHO-WPE-GIH-2021.1."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"514","DOI":"10.1016\/S0140-6736(80)92767-1","article-title":"A Simple Index of Crohn\u2019s-Disease Activity","volume":"1","author":"Harvey","year":"1980","journal-title":"Lancet"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1625","DOI":"10.1056\/NEJM198712243172603","article-title":"Coated Oral 5-Aminosalicylic Acid Therapy for Mildly to Moderately Active Ulcerative Colitis. A Randomized Study","volume":"317","author":"Schroeder","year":"1987","journal-title":"N. Engl. J. Med."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Fukuda, K., and Shinkai, Y. (2020). SETDB1-Mediated Silencing of Retroelements. Viruses, 12.","DOI":"10.3390\/v12060596"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1528","DOI":"10.4049\/jimmunol.2001003","article-title":"TRIM28 Expression on Dendritic Cells Prevents Excessive T Cell Priming by Silencing Endogenous Retrovirus","volume":"206","author":"Chikuma","year":"2021","journal-title":"J. Immunol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"9338","DOI":"10.1128\/JVI.01503-16","article-title":"NF-\u03baB and IRF1 Induce Endogenous Retrovirus K Expression via Interferon-Stimulated Response Elements in Its 5\u2019 Long Terminal Repeat","volume":"90","author":"Manghera","year":"2016","journal-title":"J. Virol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1186\/1742-4690-6-104","article-title":"B Cells and Monocytes from Patients with Active Multiple Sclerosis Exhibit Increased Surface Expression of Both HERV-H Env and HERV-W Env, Accompanied by Increased Seroreactivity","volume":"6","author":"Brudek","year":"2009","journal-title":"Retrovirology"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1952","DOI":"10.3899\/jrheum.130502","article-title":"Rheumatoid Arthritis Is Associated with IgG Antibodies to Human Endogenous Retrovirus Gag Matrix: A Potential Pathogenic Mechanism of Disease?","volume":"41","author":"Nelson","year":"2014","journal-title":"J. Rheumatol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1111\/cei.12964","article-title":"Identification of a HERV-K Env Surface Peptide Highly Recognized in Rheumatoid Arthritis (RA) Patients: A Cross-Sectional Case-Control Study","volume":"189","author":"Mameli","year":"2017","journal-title":"Clin. Exp. Immunol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1080\/08916930802024764","article-title":"Molecular Mimicry and Immunomodulation by the HRES-1 Endogenous Retrovirus in SLE","volume":"41","author":"Perl","year":"2008","journal-title":"Autoimmunity"},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Panova, V., Attig, J., Young, G.R., Stoye, J.P., and Kassiotis, G. (2020). Antibody-Induced Internalisation of Retroviral Envelope Glycoproteins Is a Signal Initiation Event. PLoS Pathog., 16.","DOI":"10.1371\/journal.ppat.1008605"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"368","DOI":"10.5483\/BMBRep.2021.54.7.246","article-title":"Expression Profiles of Human Endogenous Retrovirus (HERV)-K and HERV-R Env Proteins in Various Cancers","volume":"54","author":"Ko","year":"2021","journal-title":"BMB Rep."},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Mullins, C.S., H\u00fchns, M., Krohn, M., Peters, S., Cheynet, V., Oriol, G., Guillotte, M., Ducrot, S., Mallet, F., and Linnebacher, M. (2016). Generation, Characterization and Application of Antibodies Directed against HERV-H Gag Protein in Colorectal Samples. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0153349"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"2410","DOI":"10.1016\/j.bbagen.2012.08.006","article-title":"Major Signaling Pathways in Intestinal Stem Cells","volume":"1830","author":"Vanuytsel","year":"2013","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"4470","DOI":"10.4049\/jimmunol.1203561","article-title":"Cutting Edge: A Novel, Human-Specific Interacting Protein Couples FOXP3 to a Chromatin-Remodeling Complex That Contains KAP1\/TRIM28","volume":"190","author":"Huang","year":"2013","journal-title":"J. Immunol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"725","DOI":"10.1007\/s44197-023-00145-w","article-title":"Evolving Trends and Burden of Inflammatory Bowel Disease in Asia, 1990\u20132019: A Comprehensive Analysis Based on the Global Burden of Disease Study","volume":"13","author":"Chen","year":"2023","journal-title":"J. Epidemiol. Glob. Health"},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Caviglia, G.P., Garrone, A., Bertolino, C., Vanni, R., Bretto, E., Poshnjari, A., Tribocco, E., Frara, S., Armandi, A., and Astegiano, M. (2023). Epidemiology of Inflammatory Bowel Diseases: A Population Study in a Healthcare District of North-West Italy. J. Clin. Med., 12.","DOI":"10.3390\/jcm12020641"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"776","DOI":"10.1136\/gutjnl-2013-305304","article-title":"Long-Term Intake of Dietary Fat and Risk of Ulcerative Colitis and Crohn\u2019s Disease","volume":"63","author":"Ananthakrishnan","year":"2014","journal-title":"Gut"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"647","DOI":"10.1053\/j.gastro.2019.04.016","article-title":"Environmental Risk Factors for Inflammatory Bowel Diseases: An Umbrella Review of Meta-Analyses","volume":"157","author":"Piovani","year":"2019","journal-title":"Gastroenterology"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"5618","DOI":"10.3748\/wjg.v29.i41.5618","article-title":"Diet as an Epigenetic Factor in Inflammatory Bowel Disease","volume":"29","author":"Marangoni","year":"2023","journal-title":"World J. Gastroenterol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"595","DOI":"10.1038\/s41467-024-44841-y","article-title":"Altered DNA Methylation within DNMT3A, AHRR, LTA\/TNF Loci Mediates the Effect of Smoking on Inflammatory Bowel Disease","volume":"15","author":"Zhang","year":"2024","journal-title":"Nat. Commun."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1512","DOI":"10.1038\/s41467-020-15342-5","article-title":"Colonic Microbiota Is Associated with Inflammation and Host Epigenomic Alterations in Inflammatory Bowel Disease","volume":"11","author":"Ryan","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"400","DOI":"10.1097\/MIB.0000000000000229","article-title":"Exposome in IBD: Recent Insights in Environmental Factors That Influence the Onset and Course of IBD","volume":"21","author":"Rogler","year":"2015","journal-title":"Inflamm. Bowel Dis."},{"key":"ref_69","doi-asserted-by":"crossref","unstructured":"Ferenc, K., Sokal-Dembowska, A., Helma, K., Motyka, E., Jarmakiewicz-Czaja, S., and Filip, R. (2024). Modulation of the Gut Microbiota by Nutrition and Its Relationship to Epigenetics. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25021228"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"883","DOI":"10.1089\/aid.2010.0014","article-title":"Smoking Increases Transcription of Human Endogenous Retroviruses in a Newly Established in Vitro Cell Model and in Normal Urothelium","volume":"26","author":"Gabriel","year":"2010","journal-title":"AIDS Res. Hum. Retroviruses"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"e101107","DOI":"10.15252\/embj.2018101107","article-title":"Expression of Endogenous Retroviruses Reflects Increased Usage of Atypical Enhancers in T Cells","volume":"38","author":"Michel","year":"2019","journal-title":"EMBO J."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1016\/j.cbpa.2018.04.015","article-title":"Environmental Effects on Chromatin Repression at Imprinted Genes and Endogenous Retroviruses","volume":"45","author":"Pathak","year":"2018","journal-title":"Curr. Opin. Chem. Biol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1177\/13524585211024997","article-title":"Efficacy and Safety of Temelimab in Multiple Sclerosis: Results of a Randomized Phase 2b and Extension Study","volume":"28","author":"Hartung","year":"2022","journal-title":"Mult. Scler."},{"key":"ref_74","doi-asserted-by":"crossref","unstructured":"Gim\u00e9nez-Orenga, K., and Oltra, E. (2021). Human Endogenous Retrovirus as Therapeutic Targets in Neurologic Disease. Pharmaceuticals, 14.","DOI":"10.20944\/preprints202104.0262.v1"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"e2200260119","DOI":"10.1073\/pnas.2200260119","article-title":"Human Endogenous Retrovirus-K (HERV-K) Reverse Transcriptase (RT) Structure and Biochemistry Reveals Remarkable Similarities to HIV-1 RT and Opportunities for HERV-K-Specific Inhibition","volume":"119","author":"Baldwin","year":"2022","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"2417","DOI":"10.1097\/QAD.0b013e3282f14d64","article-title":"The Replicative Activity of Human Endogenous Retrovirus K102 (HERV-K102) with HIV Viremia","volume":"21","author":"Laderoute","year":"2007","journal-title":"AIDS"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1186\/s12977-017-0347-4","article-title":"Inhibition of Human Endogenous Retrovirus-K by Antiretroviral Drugs","volume":"14","author":"Tyagi","year":"2017","journal-title":"Retrovirology"},{"key":"ref_78","doi-asserted-by":"crossref","unstructured":"Vautrin, A., Manchon, L., Garcel, A., Campos, N., Lapasset, L., Laaref, A.M., Bruno, R., Gislard, M., Dubois, E., and Scherrer, D. (2019). Both Anti-Inflammatory and Antiviral Properties of Novel Drug Candidate ABX464 Are Mediated by Modulation of RNA Splicing. Sci. Rep., 9.","DOI":"10.1038\/s41598-018-37813-y"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"1689","DOI":"10.1093\/ecco-jcc\/jjad067","article-title":"Obefazimod: A First-in-Class Drug for the Treatment of Ulcerative Colitis","volume":"17","author":"Vermeire","year":"2023","journal-title":"J. Crohns Colitis"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"693","DOI":"10.1097\/00002030-200203290-00004","article-title":"The Human 26S Proteasome Is a Target of Antiretroviral Agents","volume":"16","author":"Piccinini","year":"2002","journal-title":"AIDS"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"895","DOI":"10.1093\/ecco-jcc\/jjad209","article-title":"Epigenetic and Metabolic Reprogramming of Fibroblasts in Crohn\u2019s Disease Strictures Reveals Histone Deacetylases as Therapeutic Targets","volume":"18","author":"Lewis","year":"2024","journal-title":"J. Crohns Colitis"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"e13222","DOI":"10.1111\/cpr.13222","article-title":"Tripartite Motif Family Proteins in Inflammatory Bowel Disease: Mechanisms and Potential for Interventions","volume":"55","author":"Chen","year":"2022","journal-title":"Cell Prolif."}],"container-title":["Viruses"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4915\/16\/10\/1570\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T16:10:53Z","timestamp":1760112653000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4915\/16\/10\/1570"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,10,5]]},"references-count":82,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2024,10]]}},"alternative-id":["v16101570"],"URL":"https:\/\/doi.org\/10.3390\/v16101570","relation":{},"ISSN":["1999-4915"],"issn-type":[{"value":"1999-4915","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,10,5]]}}}