Latent Membrane Protein 1 of Epstein–Barr Virus Promotes RIG-I Degradation Mediated by Proteasome Pathway

• Main Authors: Chongfeng Xu, Lei Sun, Wenjun Liu, Ziyuan Duan
• Format: Article
• Language: English
• Published: Frontiers Media S.A. 2018-06-01
• Series: Frontiers in Immunology
• Subjects: RIG-I; LMP1; nasopharygeal carcinoma; Epstein–Barr virus cancer; immunotherapy of cancer
• Online Access: https://www.frontiersin.org/article/10.3389/fimmu.2018.01446/full

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.