8月16日，國(guó)際學(xué)術(shù)期刊《Journal of Immunology》在線發(fā)表了中國(guó)科學(xué)院上海生物化學(xué)與細(xì)胞生物學(xué)研究所孫兵研究組題為“Negative Regulation of Nmi on Virus-Triggered Type I IFN Production by Targeting IRF7”的研究論文,。報(bào)道了病毒誘導(dǎo)的分子NMI（N-Myc and STATs interactor）可以促進(jìn)IRF7泛素化,，通過蛋白酶體途徑降解，從而抑制宿主細(xì)胞的抗病毒反應(yīng),，是一個(gè)病毒介導(dǎo)的免疫反應(yīng)負(fù)性調(diào)控蛋白,。
病毒感染宿主細(xì)胞以后，可以誘發(fā)抗病毒免疫反應(yīng),。宿主細(xì)胞的模式識(shí)別分子RIG-I和MDA-5可以識(shí)別胞內(nèi)的病毒RNA,。通過接頭分子VISA(也稱為MAVS、IPS-1或Cardif)引發(fā)下游信號(hào)分子信號(hào)傳遞,，促進(jìn)轉(zhuǎn)錄因子IRF3/IRF7和NF-kB的激活,，進(jìn)而誘導(dǎo)I型干擾素和炎性因子的產(chǎn)生，其中IRF7是誘導(dǎo)I型干擾素產(chǎn)生的關(guān)鍵性轉(zhuǎn)錄因子之一,。
孫兵研究組博士生王潔,、楊波等發(fā)現(xiàn)NMI分子可以負(fù)性調(diào)控病毒誘導(dǎo)的I型干擾素產(chǎn)生,。Sendai virus感染細(xì)胞后,，NMI分子被誘導(dǎo)表達(dá)，NMI可以作用于IRF7并促進(jìn)IRF7的K48位泛素化以及蛋白酶體途徑降解,。體外過表達(dá)NMI可以抑制IFN-a/b的表達(dá),，而下調(diào)NMI則促進(jìn)IFN-a/b的表達(dá),。進(jìn)一步在NMI轉(zhuǎn)基因小鼠身上感染Sendai virus，其肺部的IFN-a/b表達(dá)明顯降低,。
I型干擾素在抗病毒過程中發(fā)揮了關(guān)鍵的作用,，而它的表達(dá)又是受到精細(xì)的調(diào)控，過度表達(dá)將造成機(jī)體損害,。該研究揭示了一種新的抗病毒反應(yīng)調(diào)控和保持免疫平衡的機(jī)制,。
該項(xiàng)工作得到了國(guó)家科技部、國(guó)家基金委的資助,。（生物谷Bioon.com）
doi:10.4049/jimmunol.1300740
PMC:
PMID:
Negative Regulation of Nmi on Virus-Triggered Type I IFN Production by Targeting IRF7.
Wang J, Yang B, Hu Y, Zheng Y, Zhou H, Wang Y, Ma Y, Mao K, Yang L, Lin G, Ji Y, Wu X, Sun B.
Viral infection causes host cells to produce type I IFNs, which play a critical role in viral clearance. IFN regulatory factor (IRF) 7 is the master regulator of type I IFN-dependent immune responses. In this article, we report that N-Myc and STATs interactor (Nmi), a Sendai virus-inducible protein, interacted with IRF7 and inhibited virus-triggered type I IFN production. The overexpression of Nmi inhibited the Sendai virus-triggered induction of type I IFNs, whereas the knockdown of Nmi promoted IFN production. Furthermore, the enhanced production of IFNs resulting from Nmi knockdown was sufficient to protect cells from infection by vesicular stomatitis virus. In addition, Nmi was found to promote the K48-linked ubiquitination of IRF7 and the proteasome-dependent degradation of this protein. Finally, an impairment of antiviral responses is also detectable in Nmi-transgenic mice. These findings suggest that Nmi is a negative regulator of the virus-triggered induction of type I IFNs that targets IRF7.
