Identification and characterization of the anti-viral interferon lambda 3 as direct target of the Epstein-Barr virus microRNA-BART7-3p.

Autor:	Blümke J; Institute for Medical Immunology, Martin-Luther-University Halle-Wittenberg, Halle, Germany., Bauer M; Institute for Pathology, Martin-Luther-University Halle-Wittenberg, Halle, Germany., Vaxevanis C; Institute for Medical Immunology, Martin-Luther-University Halle-Wittenberg, Halle, Germany., Wilfer A; Institute for Pathology, Martin-Luther-University Halle-Wittenberg, Halle, Germany.; Krukenberg Cancer Center, University Hospital Halle, Martin-Luther-University Halle-Wittenberg, Halle, Germany., Mandelboim O; Department of Immunology, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel., Wickenhauser C; Institute for Pathology, Martin-Luther-University Halle-Wittenberg, Halle, Germany., Seliger B; Institute for Medical Immunology, Martin-Luther-University Halle-Wittenberg, Halle, Germany.; Department of Good Manufacturing Practice (GMP) Development & Advanced Therapy Medicinal Products (ATMP) Design, Fraunhofer Institute for Cell Therapy and Immunology (IZI), Leipzig, Germany.; Institute for Translational Immunology, Brandenburg Medical School (MHB), Brandenburg an der Havel, Germany., Jasinski-Bergner S; Institute for Medical Immunology, Martin-Luther-University Halle-Wittenberg, Halle, Germany.; Institute for Translational Immunology, Brandenburg Medical School (MHB), Brandenburg an der Havel, Germany.
Jazyk:	angličtina
Zdroj:	Oncoimmunology [Oncoimmunology] 2023 Nov 27; Vol. 12 (1), pp. 2284483. Date of Electronic Publication: 2023 Nov 27 (Print Publication: 2023).
DOI:	10.1080/2162402X.2023.2284483
Abstrakt:	The human Epstein-Barr virus (EBV), as a member of the human γ 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. Competing Interests: No potential conflict of interest was reported by the author(s). (© 2023 The Author(s). Published with license by Taylor & Francis Group, LLC.)
Databáze:	MEDLINE
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