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• W2743000789 abstract "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 miR-BHRF1-2-5p 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. IMPORTANCE IL-1 signaling plays an important role in inflammation and early activation of host innate immune responses following virus infection. Here, we demonstrate that a viral miRNA downregulates the IL-1 receptor 1 during EBV infection, which consequently alters the responsiveness of cells to IL-1 stimuli and changes the cytokine expression levels within infected cell populations. We postulate that this viral miRNA activity not only disrupts IL-1 autocrine and paracrine signaling loops that can alert effector cells to sites of infection but also provides a survival advantage by dampening excessive inflammation that may be detrimental to the infected cell." @default.
• W2743000789 created "2017-08-17" @default.
• W2743000789 creator A5013247732 @default.
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• W2743000789 creator A5037458498 @default.
• W2743000789 creator A5068129114 @default.
• W2743000789 creator A5087872669 @default.
• W2743000789 date "2017-11-01" @default.
• W2743000789 modified "2023-10-10" @default.
• W2743000789 title "An Epstein-Barr Virus MicroRNA Blocks Interleukin-1 (IL-1) Signaling by Targeting IL-1 Receptor 1" @default.
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• W2743000789 doi "https://doi.org/10.1128/jvi.00530-17" @default.
• W2743000789 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/5640834" @default.
• W2743000789 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/28794034" @default.
• W2743000789 hasPublicationYear "2017" @default.
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