Identification and characterization of the anti-viral interferon lambda 3 as direct target of the Epstein-Barr virus microRNA-BART7-3p
ABSTRACTThe 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...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2023-12-01
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| Series: | OncoImmunology |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/2162402X.2023.2284483 |
| _version_ | 1797367161190088704 |
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| author | Juliane Blümke Marcus Bauer Christoforos Vaxevanis Andreas Wilfer Ofer Mandelboim Claudia Wickenhauser Barbara Seliger Simon Jasinski-Bergner |
| author_facet | Juliane Blümke Marcus Bauer Christoforos Vaxevanis Andreas Wilfer Ofer Mandelboim Claudia Wickenhauser Barbara Seliger Simon Jasinski-Bergner |
| author_sort | Juliane Blümke |
| collection | DOAJ |
| description | ABSTRACTThe 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. |
| first_indexed | 2024-03-08T17:13:24Z |
| format | Article |
| id | doaj.art-ec0c7d38ed094b57973adee9d2b4259f |
| institution | Directory Open Access Journal |
| issn | 2162-402X |
| language | English |
| last_indexed | 2024-03-08T17:13:24Z |
| publishDate | 2023-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | OncoImmunology |
| spelling | doaj.art-ec0c7d38ed094b57973adee9d2b4259f2024-01-03T19:25:37ZengTaylor & Francis GroupOncoImmunology2162-402X2023-12-0112110.1080/2162402X.2023.2284483Identification and characterization of the anti-viral interferon lambda 3 as direct target of the Epstein-Barr virus microRNA-BART7-3pJuliane Blümke0Marcus Bauer1Christoforos Vaxevanis2Andreas Wilfer3Ofer Mandelboim4Claudia Wickenhauser5Barbara Seliger6Simon Jasinski-Bergner7Institute for Medical Immunology, Martin-Luther-University Halle-Wittenberg, Halle, GermanyInstitute for Pathology, Martin-Luther-University Halle-Wittenberg, Halle, GermanyInstitute for Medical Immunology, Martin-Luther-University Halle-Wittenberg, Halle, GermanyInstitute for Pathology, Martin-Luther-University Halle-Wittenberg, Halle, GermanyDepartment of Immunology, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, IsraelInstitute for Pathology, Martin-Luther-University Halle-Wittenberg, Halle, GermanyInstitute for Medical Immunology, Martin-Luther-University Halle-Wittenberg, Halle, GermanyInstitute for Medical Immunology, Martin-Luther-University Halle-Wittenberg, Halle, GermanyABSTRACTThe 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.https://www.tandfonline.com/doi/10.1080/2162402X.2023.2284483EBVEBV target genesIFNL3immune escapemicroRNA |
| spellingShingle | Juliane Blümke Marcus Bauer Christoforos Vaxevanis Andreas Wilfer Ofer Mandelboim Claudia Wickenhauser Barbara Seliger Simon Jasinski-Bergner Identification and characterization of the anti-viral interferon lambda 3 as direct target of the Epstein-Barr virus microRNA-BART7-3p OncoImmunology EBV EBV target genes IFNL3 immune escape microRNA |
| title | Identification and characterization of the anti-viral interferon lambda 3 as direct target of the Epstein-Barr virus microRNA-BART7-3p |
| title_full | Identification and characterization of the anti-viral interferon lambda 3 as direct target of the Epstein-Barr virus microRNA-BART7-3p |
| title_fullStr | Identification and characterization of the anti-viral interferon lambda 3 as direct target of the Epstein-Barr virus microRNA-BART7-3p |
| title_full_unstemmed | Identification and characterization of the anti-viral interferon lambda 3 as direct target of the Epstein-Barr virus microRNA-BART7-3p |
| title_short | Identification and characterization of the anti-viral interferon lambda 3 as direct target of the Epstein-Barr virus microRNA-BART7-3p |
| title_sort | identification and characterization of the anti viral interferon lambda 3 as direct target of the epstein barr virus microrna bart7 3p |
| topic | EBV EBV target genes IFNL3 immune escape microRNA |
| url | https://www.tandfonline.com/doi/10.1080/2162402X.2023.2284483 |
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