标题：Mint3 potentiates TLR3/4-and RIG-I-induced IFN-beta expression and antiviral immune responses
作者：Huai, Wanwan; Song, Hui; Yu, Zhongxia; Wang, Wenwen; Han, Lihui; Sakamoto, Takeharu; Seiki, Motoharu; Zhang, Lining; Zhang, Qunye; Z 更多 作者机构：[Huai, Wanwan; Song, Hui; Yu, Zhongxia; Wang, Wenwen; Han, Lihui; Zhang, Lining; Zhao, Wei] Shandong Univ, Sch Med, Dept Immunol, Jinan 250012, Shando 更多
通讯作者：Zhao, W;Zhao, W
通讯作者地址：[Zhao, W]Shandong Univ, Sch Med, Dept Immunol, Jinan 250012, Shandong, Peoples R China;[Zhao, W]Shandong Univ, Sch Med, Key Lab Infect & Immun Shandon 更多
来源：PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
关键词：interferon; viral infection; TLR; RIG-I; TRAF3
摘要：Type I IFNs (IFN-alpha/beta) play crucial roles in the elimination of invading viruses. Multiple immune cells including macrophages recognize viral infection through a variety of pattern recognition receptors, such as Toll-like receptors (TLRs) and retinoic acid-inducible gene-I (RIG-I)-like receptors, and initiate type I IFN secretion and subsequent antiviral immune responses. However, the mechanisms by which host immune cells can produce adequate amounts of type I IFNs and then eliminate viruses effectively remain to be further elucidated. In the present study, we show that munc18-1-interacting protein 3 (Mint3) expression can be markedly induced during viral infection in macrophages. Mint3 enhances TLR3/4- and RIG-I-induced IRF3 activation and IFN-beta production by promoting K63-linked polyubiquitination of TNF receptor-associated factor 3 (TRAF3). Consistently, Mint3 deficiency greatly attenuated antiviral immune responses and increased viral replication. Therefore, we have identified Mint3 as a physiological positive regulator of TLR3/4 and RIG-I-induced IFN-beta production and have outlined a feedback mechanism for the control of antiviral immune responses.