Epstein-Barr virus nuclear antigen EBNA3A modulates IRF3-dependent IFNβ expression.

Autor:	Landman SL; Department of Cell and Chemical Biology, Leiden University Medical Center (LUMC), Leiden, the Netherlands; Oncode Institute, Leiden University Medical Center (LUMC), Leiden, the Netherlands., Ressing ME; Department of Cell and Chemical Biology, Leiden University Medical Center (LUMC), Leiden, the Netherlands., Gram AM; Department of Cell and Chemical Biology, Leiden University Medical Center (LUMC), Leiden, the Netherlands., Tjokrodirijo RTN; Center for Proteomics & Metabolomics, LUMC, Leiden, the Netherlands., van Veelen PA; Center for Proteomics & Metabolomics, LUMC, Leiden, the Netherlands., Neefjes J; Department of Cell and Chemical Biology, Leiden University Medical Center (LUMC), Leiden, the Netherlands; Oncode Institute, Leiden University Medical Center (LUMC), Leiden, the Netherlands., Hoeben RC; Department of Cell and Chemical Biology, Leiden University Medical Center (LUMC), Leiden, the Netherlands., van der Veen AG; Department of Immunology, LUMC, Leiden, the Netherlands., Berlin I; Department of Cell and Chemical Biology, Leiden University Medical Center (LUMC), Leiden, the Netherlands; Oncode Institute, Leiden University Medical Center (LUMC), Leiden, the Netherlands. Electronic address: i.berlin@lumc.nl.
Jazyk:	angličtina
Zdroj:	The Journal of biological chemistry [J Biol Chem] 2024 Sep; Vol. 300 (9), pp. 107645. Date of Electronic Publication: 2024 Aug 08.
DOI:	10.1016/j.jbc.2024.107645
Abstrakt:	Epstein-Barr virus (EBV), the causative agent of infectious mononucleosis, persistently infects over 90% of the human adult population and is associated with several human cancers. To establish life-long infection, EBV tampers with the induction of type I interferon (IFN I)-dependent antiviral immunity in the host. How various EBV genes help orchestrate this crucial strategy is incompletely defined. Here, we reveal a mechanism by which the EBV nuclear antigen 3A (EBNA3A) may inhibit IFNβ induction. Using proximity biotinylation we identify the histone acetyltransferase P300, a member of the IFNβ transcriptional complex, as a binding partner of EBNA3A. We further show that EBNA3A also interacts with the activated IFN-inducing transcription factor interferon regulatory factor 3 that collaborates with P300 in the nucleus. Both events are mediated by the N-terminal domain of EBNA3A. We propose that EBNA3A limits the binding of interferon regulatory factor 3 to the IFNβ promoter, thereby hampering downstream IFN I signaling. Collectively, our findings suggest a new mechanism of immune evasion by EBV, affected by its latency gene EBNA3A. Competing Interests: Conflict of interest The authors declare that they have no conflicts of interest with the contents of this article. (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu