Intracellular osteopontin stabilizes TRAF3 to positively regulate innate antiviral response.
Intracellular osteopontin stabilizes TRAF3 to positively regulate innate antiviral response.
复制标题
细胞内骨桥蛋白稳定 TRAF3 以积极调节先天抗病毒反应
DOI：
10.1038/srep23771
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发表时间：
2016-03-30
影响因子：
4.6
通讯作者：
Gao C
中科院分区：
文献类型：
--
作者：
Zhao K;Zhang M;Zhang L;Wang P;Song G;Liu B;Wu H;Yin Z;Gao C
骨桥蛋白（OPN）是一种多功能蛋白，参与先天免疫和获得性免疫。然而，OPN，尤其是胞内型OPN（iOPN）在天然抗病毒免疫应答中的作用仍不清楚。在这里，我们证明了iOPN是保护宿主免受病毒感染的重要正调节因子。OPN缺陷或敲低显著减弱病毒诱导的IRF 3活化、IFN-β产生和抗病毒应答。一致地，OPN缺陷型小鼠比WT小鼠更易受VSV感染。在机制上，发现iOPN与肿瘤坏死因子受体（TNFR）相关因子3（TRAF 3）相互作用，并通过iOPN的C末端片段抑制Triad 3A介导的K48连接的多聚泛素化和TRAF 3降解。因此，我们的研究结果描绘了iOPN的新功能，即通过稳定TRAF 3在先天性抗病毒免疫中充当正调节剂。
Osteopontin (OPN) is a multifunctional protein involved in both innate immunity and adaptive immunity. However, the function of OPN, especially the intracellular form OPN (iOPN) on innate antiviral immune response remains elusive. Here, we demonstrated that iOPN is an essential positive regulator to protect the host from virus infection. OPN deficiency or knockdown significantly attenuated virus-induced IRF3 activation, IFN-β production and antiviral response. Consistently, OPN-deficient mice were more susceptible to VSV infection than WT mice. Mechanistically, iOPN was found to interact with tumor necrosis factor receptor (TNFR)-associated factor 3 (TRAF3) and inhibit Triad3A-mediated K48-linked polyubiquitination and degradation of TRAF3 through the C-terminal fragment of iOPN. Therefore, our findings delineated a new function for iOPN to act as a positive regulator in innate antiviral immunity through stabilization of TRAF3.