Epstein-Barr Virus Envelope Glycoprotein gp110 Inhibits IKKi-Mediated Activation of NF-κB and Promotes the Degradation of β-Catenin
Yingjie Guo, Lingxia Pan, Liding Wang, Shuai Wang, Jiangqin Fu, Wenqi Luo, Kezhen Wang, Xiaoqing Li, Chen Huang, Yintao Liu, Haoran Kang, Qiyuan Zeng, Xiuxia Fu, Zejin Huang, Wanying Li, Yingxin He, Linhai Li, Tao Peng, Haidi Yang, Meili Li, Bin Xiao, Mingsheng Cai
Abstract
Epstein-Barr virus (EBV) is a ubiquitous pathogen that infects almost all human beings, and the persistence of EBV in the host is largely due to immune escape mediated by its encoded products. Thus, elucidation of EBV's immune escape mechanisms will provide a new direction for the design of novel antiviral strategies and vaccine development. Here, we report that EBV-encoded gp110 serves as a novel viral immune evasion factor, which inhibits RIG-I-like receptor pathway-mediated interferon-β (IFN-β) production. Furthermore, we found that gp110 targeted two key proteins, inhibitor of NF-κB kinase (IKKi) and β-catenin, which mediate antiviral activity and the production of IFN-β. gp110 inhibited K63-linked polyubiquitination of IKKi and induced β-catenin degradation via the proteasome, resulting in decreased IFN-β production. In summary, our data provide new insights into the EBV-mediated immune evasion surveillance strategy.