PNAS:山东大学赵伟研究组发表抗病毒免疫研究成果
近日，国际著名学术期刊《美国国家科学院院刊》杂志在线发表了山东大学基础医学院免疫学系赵伟教授课题组的研究成果“Mint3 potentiates TLR3/4- and RIG-I-induced IFN-β expression and antiviral immune responses”(“Mint3促进TLR3/4和RIG-I介导的IFN-β产生及抗病毒免疫反应”)。研究生怀婉婉和宋慧为共同第一作者，赵伟教授为论文通讯作者。
病毒性疾病时刻威胁人类健康，如乙型肝炎和2002年曾在我国流行的SARS等。因此，如何有效预防和控制病毒性疾病的发生和流行，是医学领域的重大需求。天然免疫作为人体的第一道防线，在抗病毒感染中发挥非常重要的作用，也是设计疫苗和抗病毒药物的理想靶点。病毒感染可诱导多种宿主因子表达，组成一个天然免疫的调节网络，共同参与机体抗病毒免疫反应的调控。赵伟教授课题组发现病毒感染可诱导Mint3表达;Mint3可通过促进抗病毒信号通路中的关键分子TRAF3的聚集和泛素化修饰，进而反馈性促进I型干扰素的分泌。Mint3基因缺失，可导致病毒在体内复制增多，组织损伤加重。因此，Mint3在机体抗病毒感染中发挥重要的信号增强作用。这一研究成果以病毒与宿主相互作用为切入点, 进一步揭示了抗病毒天然免疫信号网络;通过发现病毒、宿主相互作用的关键节点分子，可为抗病毒药物研制提供更为理想的靶点。
原文链接：
Mint3 potentiates TLR3/4- and RIG-I–induced IFN-β expression and antiviral immune responses
原文摘要：
Type I IFNs (IFN-α/β) 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-β 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-β production and have outlined a feedback mechanism for the control of antiviral immune responses.
作者：赵伟
