N-myc and STAT interactor degrades interferon regulatory factor 7 mediated type I interferon signaling to promote duck Tembusu virus replication

N-myc 和 STAT 相互作用蛋白降解干扰素调节因子 7 介导的 I 型干扰素信号传导,促进鸭坦布苏病毒复制

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作者:Wanshuang Luo, Wenjun Cai, Anchun Cheng, Mingshu Wang, Shun Chen, Juan Huang, Qiao Yang, Ying Wu, Di Sun, Dekang Zhu, Mafeng Liu, Xinxin Zhao, Shaqiu Zhang, Xumin Ou, Bin Tian, Zhongqiong Yin, Renyong Jia

Abstract

N-myc and STAT interactor (NMI) is an interferon-induced protein, which plays a variety of biological functions by participating in signal transduction and transcriptional activation, it has been reported to regulate antiviral response of different viruses in many species. However, the role of NMI in ducks during Duck Tembusu Virus (DTMUV) infection is completely unknown. In order to reveal whether duck NMI (duNMI) is involved in the antiviral response in the process of DTMUV infection and its role, we cloned and identified duNMI gene, and conducted sequence analysis of duNMI, the open reading frame region of duNMI gene is 1,137 bp, encoding 378 amino acid residues (aa), including 3 domains, Coiled-coil domain (22-126aa), NMI/IFP 35 domain 1 (NID1) domain (174-261aa) and NMI/IFP 35 domain 2 (NID2) domain (272-360aa). Analysis of tissue distribution of duNMI in 7-day-old ducks shows that the expression of duNMI is the highest in harderian gland, followed by small intestine and pancreas. Subsequently, we found that mRNA level of duNMI increases significantly after DTMUV stimulation, and overexpression of duNMI inhibits DTMUV replication in a dose-dependent manner. Besides, duNMI inhibits the transcriptional activity of IFN-I related cytokines. Specifically, we confirmed that duNMI interacts with duck regulatory factor 7 (duIRF7) through NID1 and NID2 domains and inhibit its expression and activated-IFN-β. These results support that duNMI is an inhibitor of antiviral innate immune response in the process of DTMUV infection, which will provide a theoretical basis for the prevention of DTMUV infection.

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