An Epstein-Barr virus microRNA blocks interleukin-1 (IL-1) signaling by targeting IL-1 receptor 1

Camille M. Skinner, Nikita S. Ivanov, Sarah A. Barr, Yan Chen, Rebecca Skalsky

Research output: Contribution to journalArticle

20 Scopus citations

Abstract

Epstein-Barr virus (EBV) encodes > 44 viral microRNAs (miRNAs) that are differentially expressed throughout infection, can be detected in Epstein-Barr virus (EBV)-positive tumors, and manipulate several biological processes, including cell proliferation, apoptosis, and immune responses. Here, we show that EBV BHRF1-2 miRNAs block NF-κB activation following treatment with proinflammatory cytokines, specifically interleukin-1β (IL-1β). Analysis of EBV PAR-CLIP miRNA targetome data sets combined with pathway analysis revealed multiple BHRF1-2 miRNA targets involved in interleukin signaling pathways. By further analyzing changes in cellular gene expression patterns, we identified the IL-1 receptor 1 (IL1R1) as a direct target of miR-BHRF1-2-5p. Targeting the IL1R1 3= untranslated region (UTR) by EBV miRBHRF1- 2-5p was confirmed using 3=-UTR luciferase reporter assays and Western blot assays. Manipulation of EBV BHRF1-2 miRNA activity in latently infected B cells altered steady-state cytokine levels and disrupted IL-1β responsiveness. These studies demonstrate functionally relevant BHRF1-2 miRNA interactions during EBV infection, which is an important step in understanding their roles in pathogenesis.

Original languageEnglish (US)
Article numbere00530-17
JournalJournal of Virology
Volume91
Issue number21
DOIs
StatePublished - Nov 1 2017

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Keywords

  • Cytokines
  • Epstein-Barr virus
  • Herpesviruses
  • Interleukins
  • microRNA
  • RNA interference

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

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