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

Juliane Blümke, Marcus Bauer, Christoforos Vaxevanis, Andreas Wilfer, Ofer Mandelboim, Claudia Wickenhauser, Barbara Seliger, Simon Jasinski-Bergner*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

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.

Original languageAmerican English
Article number2284483
JournalOncoImmunology
Volume12
Issue number1
DOIs
StatePublished - 2023

Bibliographical note

Publisher Copyright:
© 2023 The Author(s). Published with license by Taylor & Francis Group, LLC.

Keywords

  • EBV
  • EBV target genes
  • IFNL3
  • immune escape
  • microRNA

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