PMID- 38126030 OWN - NLM STAT- MEDLINE DCOM- 20231222 LR - 20231222 IS - 2162-402X (Electronic) IS - 2162-4011 (Print) IS - 2162-4011 (Linking) VI - 12 IP - 1 DP - 2023 TI - Identification and characterization of the anti-viral interferon lambda 3 as direct target of the Epstein-Barr virus microRNA-BART7-3p. PG - 2284483 LID - 10.1080/2162402X.2023.2284483 [doi] LID - 2284483 AB - The human Epstein-Barr virus (EBV), as a member of the human gamma herpes viruses (HHV), is known to be linked with distinct tumor types. It is a double-stranded DNA virus and its genome encodes among others for 48 different microRNAs (miRs). Current research demonstrated a strong involvement of certain EBV-miRs in molecular immune evasion mechanisms of infected cells by, e.g., the disruption of human leukocyte antigen (HLA) class Ia and NKG2D functions. To determine novel targets of EBV-miRs involved in immune surveillance, ebv-miR-BART7-3p, an EBV-encoded miR with high expression levels during the different lytic and latent EBV life cycle phases, was overexpressed in human HEK293T cells. Using a cDNA microarray-based comparative analysis, 234 (229 downregulated and 5 upregulated) deregulated human transcripts were identified in ebv-miR-BART7-3p transfectants, which were mainly involved in cellular processes and molecular binding. A statistically significant downregulation of the anti-proliferative and tumor-suppressive hsa-miR-34A and the anti-viral interferon lambda (IFNL)3 mRNA was found. The ebv-miR-BART7-3p-mediated downregulation of IFNL3 expression was due to a direct interaction with the IFNL3 3'-untranslated region (UTR) as determined by luciferase reporter gene assays including the identification of the accurate ebv-miR-BART7-3p binding site. The effect of ebv-miR-BART7-3p on the IFNL3 expression was validated both in human cell lines in vitro and in human tissue specimen with known EBV status. These results expand the current knowledge of EBV-encoded miRs and their role in immune evasion, pathogenesis and malignant transformation. CI - (c) 2023 The Author(s). Published with license by Taylor & Francis Group, LLC. FAU - Blumke, Juliane AU - Blumke J AD - Institute for Medical Immunology, Martin-Luther-University Halle-Wittenberg, Halle, Germany. FAU - Bauer, Marcus AU - Bauer M AD - Institute for Pathology, Martin-Luther-University Halle-Wittenberg, Halle, Germany. FAU - Vaxevanis, Christoforos AU - Vaxevanis C AD - Institute for Medical Immunology, Martin-Luther-University Halle-Wittenberg, Halle, Germany. FAU - Wilfer, Andreas AU - Wilfer A AD - Institute for Pathology, Martin-Luther-University Halle-Wittenberg, Halle, Germany. AD - Krukenberg Cancer Center, University Hospital Halle, Martin-Luther-University Halle-Wittenberg, Halle, Germany. FAU - Mandelboim, Ofer AU - Mandelboim O AD - Department of Immunology, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel. FAU - Wickenhauser, Claudia AU - Wickenhauser C AD - Institute for Pathology, Martin-Luther-University Halle-Wittenberg, Halle, Germany. FAU - Seliger, Barbara AU - Seliger B AD - Institute for Medical Immunology, Martin-Luther-University Halle-Wittenberg, Halle, Germany. AD - Department of Good Manufacturing Practice (GMP) Development & Advanced Therapy Medicinal Products (ATMP) Design, Fraunhofer Institute for Cell Therapy and Immunology (IZI), Leipzig, Germany. AD - Institute for Translational Immunology, Brandenburg Medical School (MHB), Brandenburg an der Havel, Germany. FAU - Jasinski-Bergner, Simon AU - Jasinski-Bergner S AD - Institute for Medical Immunology, Martin-Luther-University Halle-Wittenberg, Halle, Germany. AD - Institute for Translational Immunology, Brandenburg Medical School (MHB), Brandenburg an der Havel, Germany. LA - eng PT - Journal Article DEP - 20231127 PL - United States TA - Oncoimmunology JT - Oncoimmunology JID - 101570526 RN - 0 (MicroRNAs) RN - 0 (Interferon Lambda) RN - 0 (Antiviral Agents) SB - IM MH - Humans MH - *MicroRNAs/genetics MH - Herpesvirus 4, Human/genetics/metabolism MH - *Epstein-Barr Virus Infections/genetics/pathology MH - HEK293 Cells MH - Interferon Lambda MH - *Nasopharyngeal Neoplasms/genetics/metabolism/pathology MH - Antiviral Agents PMC - PMC10732682 OTO - NOTNLM OT - EBV OT - EBV target genes OT - IFNL3 OT - immune escape OT - microRNA COIS- No potential conflict of interest was reported by the author(s). EDAT- 2023/12/21 06:42 MHDA- 2023/12/22 06:42 PMCR- 2023/11/27 CRDT- 2023/12/21 04:26 PHST- 2023/12/22 06:42 [medline] PHST- 2023/12/21 06:42 [pubmed] PHST- 2023/12/21 04:26 [entrez] PHST- 2023/11/27 00:00 [pmc-release] AID - 2284483 [pii] AID - 10.1080/2162402X.2023.2284483 [doi] PST - epublish SO - Oncoimmunology. 2023 Nov 27;12(1):2284483. doi: 10.1080/2162402X.2023.2284483. eCollection 2023.