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Duck IFIT5 differentially regulates Tembusu virus replication and inhibits virus-triggered innate immune response
Cytokine ( IF 3.8 ) Pub Date : 2020-09-01 , DOI: 10.1016/j.cyto.2020.155161
Xuedong Wu 1 , Ke Liu 1 , Renyong Jia 2 , Yuhong Pan 1 , Mingshu Wang 2 , Shun Chen 2 , Mafeng Liu 2 , Dekang Zhu 2 , Xinxin Zhao 2 , Ying Wu 2 , Qiao Yang 2 , Shaqiu Zhang 2 , Juan Huang 2 , Ling Zhang 2 , Yunya Liu 2 , Bin Tian 1 , Leichang Pan 1 , Yanling Yu 1 , Mujeeb Ur Rehman 1 , Zhongqiong Yin 3 , Bo Jing 3 , Anchun Cheng 2
Affiliation  

Mammalian interferon-induced protein with tetratricopeptide repeats family proteins (IFITs) play important roles in host innate immune response to viruses. Recently, studies have shown that IFIT from poultry also plays a crucial part in antiviral function. This study first reports the regulation of duck Tembusu virus (DTMUV) replication by IFIT5 and the effect of duck IFIT5 (duIFIT5) on the innate immune response after DTMUV infection. Firstly, duIFIT5 was obviously increased in duck embryo fibroblast cells (DEFs) infected with DTMUV. Compared to the negative control, we found that in the duIFIT5-overexpressing group, the DTMUV titer at 24 h post infection (hpi) was significantly reduced, but the viral titer was strikingly increased at 48 hpi. Moreover, overexpression of duIFIT5 could significantly inhibit IFN-β transcription and IFN-β promoter activation at indicated time points after DTMUV infection. Further, in DTMUV-infected or poly(I:C)-stimulated DEFs, overexpression of duIFIT5 also significantly inhibited the activation of NF-κB and IRF7 promoters, as well as the activation of downstream IFN induced the interferon-stimulated response element (ISRE) promoter. Meanwhile, the transcription level of antiviral protein Mx, but not OASL, was obviously decreased at various time points. The opposite results were obtained by knockdown of duIFIT5 in DTMUV-infected or poly(I:C)-stimulated DEFs. Compared to the negative control, knockdown of duIFIT5 promoted DTMUV titer and DTMUV envelope (E) protein expression at 24 hpi, but DTMUV titer and E protein expression was markedly decreased at 48 hpi. Additionally, the promoters of IFN-β, NF-κB, IRF7 and ISRE were significantly activated in the duIFIT5 knockdown group. Collectively, duIFIT5 differentially regulates DTMUV replication and inhibits virus-triggered innate immune response.

中文翻译:

鸭子IFIT5差异调节Tembusu病毒复制并抑制病毒触发的先天免疫反应

哺乳动物干扰素诱导蛋白与四肽重复家族蛋白 (IFIT) 在宿主对病毒的先天免疫反应中发挥重要作用。最近,研究表明来自家禽的 IFIT 在抗病毒功能中也起着至关重要的作用。本研究首次报道了IFIT5对鸭坦布苏病毒(DTMUV)复制的调控以及鸭IFIT5(duIFIT5)对DTMUV感染后先天免疫反应的影响。首先,DTMUV感染的鸭胚胎成纤维细胞(DEFs)中duIFIT5明显增加。与阴性对照相比,我们发现在 duIFIT5 过表达组中,感染后 24 小时 (hpi) 的 DTMUV 滴度显着降低,但病毒滴度在 48 hpi 时显着增加。而且,在 DTMUV 感染后的指定时间点,duIFIT5 的过表达可以显着抑制 IFN-β 转录和 IFN-β 启动子激活。此外,在 DTMUV 感染或 poly(I:C) 刺激的 DEF 中,duIFIT5 的过表达也显着抑制了 NF-κB 和 IRF7 启动子的激活,以及下游 IFN 的激活诱导了干扰素刺激反应元件 (ISRE) ) 发起人。同时,抗病毒蛋白 Mx 的转录水平,而非 OASL,在不同时间点明显降低。通过在 DTMUV 感染或聚 (I:C) 刺激的 DEF 中敲除 duIFIT5,获得了相反的结果。与阴性对照相比,duIFIT5 的敲低在 24 hpi 时促进了 DTMUV 滴度和 DTMUV 包膜(E)蛋白表达,但 DTMUV 滴度和 E 蛋白表达在 48 hpi 时显着降低。此外,在duIFIT5敲低组中,IFN-β、NF-κB、IRF7和ISRE的启动子被显着激活。总的来说,duIFIT5 差异调节 DTMUV 复制并抑制病毒触发的先天免疫反应。
更新日期:2020-09-01
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