Epstein-Barr virus envelope glycoprotein 110 inhibits NF-κB activation by interacting with NF-κB subunit p65.
Epstein-Barr virus envelope glycoprotein 110 inhibits NF-κB activation by interacting with NF-κB subunit p65.
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eb病毒包膜糖蛋白110通过与NF-κB亚基p65相互作用抑制NF-κB活化。
DOI：
10.1016/j.jbc.2023.104613
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发表时间：
2023-05
影响因子：
4.8
通讯作者：
Li, Meili
中科院分区：
文献类型：
--
作者：
Cai, Mingsheng;Xiao, Bin;Wang, Yuanfang;Wang, Kezhen;Luo, Wenqi;Fu, Jiangqin;Wang, Shuai;Deng, Shenyu;Li, Bolin;Gong, Lan;Zhong, Jiayi;Hu, Li;Pan, Lingxia;Wang, Liding;Liu, Yintao;Huang, Chen;Li, Xiaoqing;Zeng, Qiyuan;Kang, Haoran;Li, Linhai;Zan, Jie;Peng, Tao;Yang, Haidi;Li, Meili
EB病毒（Epstein-Barr virus，EBV）是嗜淋巴细胞病毒家族的成员，与人类恶性肿瘤密切相关。据报道，包膜糖蛋白110（gp 110）在EB病毒的融合、DNA复制和核衣壳组装中起着重要作用。然而，尚未确定gp 110是否参与调节宿主的先天免疫。在本研究中，我们发现gp 110在生理条件下抑制肿瘤坏死因子α介导的NF- κB启动子活性和下游NF- κ B调节的细胞因子的产生。使用双荧光素酶报告基因分析，我们发现gp 110可能阻碍NF-κB反式激活亚基p65下游的NF-κB启动子激活。随后，我们使用免疫共沉淀试验证明，gp 110相互作用与p65在EB病毒裂解感染，和C-末端的gp 110的胞质区域是关键的相互作用域与p65。此外，我们确定，gp 110可以结合到N-末端Rel同源和C-末端结构域的p65。另外，gp 110可能不会干扰p65与非反式激活亚基p50的关联，但我们发现它抑制了p65的激活磷酸化（在Ser 536）和核转位，我们还发现这是由gp 110的C-末端胞质区域执行的。这些结果提示，gp 110蛋白可能是EBV对抗宿主天然免疫反应的重要成分，这对揭示EBV的感染性和致病机制也有一定的帮助。
Epstein–Barr virus (EBV) is a member of the lymphotropic virus family and is highly correlated with some human malignant tumors. It has been reported that envelope glycoprotein 110 (gp110) plays an essential role in viral fusion, DNA replication, and nucleocapsid assembly of EBV. However, it has not been established whether gp110 is involved in regulating the host's innate immunity. In this study, we found that gp110 inhibits tumor necrosis factor α–mediated NF- κB promoter activity and the downstream production of NF- κB-regulated cytokines under physiological conditions. Using dual-luciferase reporter assays, we showed that gp110 might impede the NF-κB promoter activation downstream of NF-κB transactivational subunit p65. Subsequently, we used coimmunoprecipitation assays to demonstrate that gp110 interacts with p65 during EBV lytic infection, and that the C-terminal cytoplasmic region of gp110 is the key interaction domain with p65. Furthermore, we determined that gp110 can bind to the N-terminal Rel homologous and C-terminal domains of p65. Alternatively, gp110 might not disturb the association of p65 with nontransactivational subunit p50, but we showed it restrains activational phosphorylation (at Ser536) and nuclear translocation of p65, which we also found to be executed by the C-terminal cytoplasmic region of gp110. Altogether, these data suggest that the surface protein gp110 may be a vital component for EBV to antagonize the host's innate immune response, which is also helpful for revealing the infectivity and pathogenesis of EBV.
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