Guanylate Binding Protein 4 Negatively Regulates Virus-Induced Type I IFN and Antiviral Response by Targeting IFN Regulatory Factor 7
Guanylate Binding Protein 4 Negatively Regulates Virus-Induced Type I IFN and Antiviral Response by Targeting IFN Regulatory Factor 7
复制标题
鸟苷酸结合蛋白 4 通过靶向 IFN 调节因子 7 负向调节病毒诱导的 I 型 IFN 和抗病毒反应
DOI：
10.4049/jimmunol.1003691
复制
发表时间：
2011-12-15
影响因子：
4.4
通讯作者：
Sun, Bing
中科院分区：
文献类型：
--
作者：
Hu, Yu;Wang, Jie;Sun, Bing
IRF7被认为是病毒触发诱导I型ifn （IFN-I）的主调控因子。在这项研究中，我们发现GBP4病毒诱导的蛋白与IRF7相互作用，作为IFN-I反应的负调节因子。GBP4的过表达抑制病毒触发的irf7依赖性信号的激活，但对NF-kappa B信号没有影响，而GBP4的敲低则有相反的作用。此外，仙台病毒感染细胞中GBP4被沉默的上清液更有效地抑制了水泡性口炎病毒的复制。竞争性共免疫沉淀实验表明，过表达GBP4会破坏TRAF6和IRF7之间的相互作用，导致TRAF6介导的IRF7泛素化受损。我们的研究结果表明，GBP4是病毒引发的IFN-I产生的负调节因子，并且被鉴定为靶向IRF7并抑制其功能的新蛋白。中华免疫学杂志，2011,18(7):656 - 662。
IRF7 is known as the master regulator in virus-triggered induction of type I IFNs (IFN-I). In this study, we identify GBP4 virus-induced protein interacting with IRF7 as a negative regulator for IFN-I response. Overexpression of GBP4 inhibits virus-triggered activation of IRF7-dependent signaling, but has no effect on NF-kappa B signaling, whereas the knockdown of GBP4 has opposite effects. Furthermore, the supernatant from Sendai virus-infected cells in which GBP4 have been silenced inhibits the replication of vesicular stomatitis virus more efficiently. Competitive coimmunoprecipitation experiments indicate that overexpression of GBP4 disrupts the interactions between TRAF6 and IRF7, resulting in impaired TRAF6-mediated IRF7 ubiquitination. Our results suggest that GBP4 is a negative regulator of virus-triggered IFN-I production, and it is identified as a novel protein targeting IRF7 and inhibiting its function. The Journal of Immunology, 2011, 187: 6456-6462.