Xu Chongfeng, Sun Lei, Liu Wenjun, Duan Ziyuan
Genetic Resources Center, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, China.
CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China.
Front Immunol. 2018 Jun 28;9:1446. doi: 10.3389/fimmu.2018.01446. eCollection 2018.
RIG-I signaling is critical to host innate immune response against RNA virus infection, and also can be activated against many kinds of cancer. Oncogene LMP1 of Epstein-Barr virus (EBV) contributes to various tumors progress. In this study, we have provided strong evidence that LMP1 inhibits Sendai virus mediated type I interferon production and downregulates RIG-I signaling pathway by promotion RIG-I degradation dependent on proteasome. Nineteen kinds of E3 ligase are identified by IP-MS as LMP1-interactors, they are candidate E3s, which are possibly recruited by LMP1 to mediate RIG-I degradation. CHIP is among these E3s, which has been reported to lead RIG-I degradation. Notably, we find C666-1, an EBV-positive nasopharyngeal carcinoma cell line, expresses low level of RIG-I, even treated with IFN-α, RIG-I expression could not be induced. This evidence indicates that EBV employs a unique strategy to evade RIG-I mediated immune responses.
维甲酸诱导基因I（RIG-I）信号传导对于宿主针对RNA病毒感染的固有免疫反应至关重要，并且也可针对多种癌症被激活。爱泼斯坦-巴尔病毒（EBV）的癌基因潜伏膜蛋白1（LMP1）促进各种肿瘤进展。在本研究中，我们提供了强有力的证据表明，LMP1抑制仙台病毒介导的I型干扰素产生，并通过促进依赖蛋白酶体的RIG-I降解来下调RIG-I信号通路。通过免疫沉淀-质谱法（IP-MS）鉴定出19种E3连接酶为LMP1相互作用蛋白，它们是候选E3s，可能被LMP1招募以介导RIG-I降解。CHIP是这些E3s之一，据报道它可导致RIG-I降解。值得注意的是，我们发现EBV阳性鼻咽癌细胞系C666-1表达低水平的RIG-I，即使在用α-干扰素处理后，RIG-I表达也不能被诱导。这一证据表明EBV采用独特策略逃避RIG-I介导的免疫反应。
