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.
摘要：
EB病毒(EBV)传染性单核细胞增多症的病原体，持续感染超过90％的成年人，并与几种人类癌症有关。为了建立终身感染，EBV干预宿主中I型干扰素（IFNI）依赖性抗病毒免疫的诱导。各种EBV基因如何帮助协调这一关键策略还没有完全定义。这里,我们揭示了EBV核抗原3A（EBNA3A）可能抑制IFNβ诱导的机制。使用邻近生物素化，我们鉴定了组蛋白乙酰转移酶P300，IFNβ转录复合物的成员，作为EBNA3A的结合伴侣。我们进一步表明，EBNA3A还与激活的IFN诱导转录因子IRF3相互作用，该因子与细胞核中的P300协作。这两个事件均由EBNA3A的N末端结构域介导。我们建议EBNA3A限制IRF3与IFNβ启动子的结合，从而阻碍下游IFNI信号传导。总的来说，我们的发现提示了一种新的EBV免疫逃避机制，受其潜伏期基因EBNA3A的影响。
