IFITM3 inhibits virus-triggered induction of type I interferon by mediating autophagosome-dependent degradation of IRF3
IFITM3 inhibits virus-triggered induction of type I interferon by mediating autophagosome-dependent degradation of IRF3
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IFITM3 通过介导自噬体依赖性 IRF3 降解来抑制病毒触发的 I 型干扰素诱导
DOI：
10.1038/cmi.2017.15
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发表时间：
2018-09-01
影响因子：
24.1
通讯作者：
Liu, Yu
中科院分区：
文献类型：
--
作者：
Jiang, Li-Qun;Xia, Tian;Liu, Yu
干扰素诱导的跨膜蛋白 3 (IFITM3) 是一种限制因子，可由病毒感染和干扰素 (IFN) 诱导。它抑制许多病毒的进入和复制，这些病毒与受体的使用无关，但依赖于内体中发生的过程。在这项研究中，我们证明 IFITM3 在以负反馈方式调节 RNA 病毒触发的 IFN-β 产生中发挥重要作用。 IFITM3 的过表达抑制仙台病毒触发的 IFN-β 诱导，而 IFITM3 的敲低则具有相反的效果。我们还表明，IFITM3 与 IRF3 组成性相关，并通过介导 IRF3 的自噬降解来调节 IRF3 的稳态。这些发现表明 IFITM3 对 RNA 病毒触发的 I 型 IFN 产生和细胞抗病毒反应具有新的抑制功能。
Interferon-induced transmembrane protein 3 (IFITM3) is a restriction factor that can be induced by viral infection and interferons (IFNs). It inhibits the entry and replication of many viruses, which are independent of receptor usage but dependent on processes that occur in endosomes. In this study, we demonstrate that IFITM3 plays important roles in regulating the RNA-virus-triggered production of IFN-β in a negative-feedback manner. Overexpression of IFITM3 inhibited Sendai virus-triggered induction of IFN-β, whereas knockdown of IFITM3 had the opposite effect. We also showed that IFITM3 was constitutively associated with IRF3 and regulated the homeostasis of IRF3 by mediating the autophagic degradation of IRF3. These findings suggest a novel inhibitory function of IFITM3 on the RNA-virus-triggered production of type I IFNs and cellular antiviral responses.