{Reference Type}: Journal Article
{Title}: Epstein-Barr virus nuclear antigen EBNA3A modulates IRF3-dependent IFNβ expression.
{Author}: Landman SL;Ressing ME;Gram AM;Tjokrodirijo RTN;van Veelen PA;Neefjes J;Hoeben RC;van der Veen AG;Berlin I;
{Journal}: J Biol Chem
{Volume}: 300
{Issue}: 9
{Year}: 2024 Aug 8
暂无{DOI}: 10.1016/j.jbc.2024.107645
{Abstract}: 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.