ID: 130
ID: 130
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编号：130
DOI：
10.1016/j.cyto.2015.08.157
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发表时间：
2015
期刊：
影响因子：
3.8
通讯作者：
Giotis E
中科院分区：
文献类型：
--
作者：
Giotis E
我们利用重组鸡IFN-α和适应CEF的传染性法氏囊病病毒疫苗株PBG98，在正常和刺激条件下，对日益流行的鸡DF-1细胞系及其原代祖鸡胚成纤维细胞（CEF）进行了微阵列分析。我们发现，与CEF相比，DF-1细胞具有较弱的先天免疫反应，并且鸡SOCS1 (ChSOCS1)，一种细胞因子信号的负调节因子，在DF-1细胞中的表达水平比CEF高13倍。我们发现，在CEF中过表达ChSOCS1降低了对病毒感染的磷酸化STAT1蛋白水平，但其“SOCS盒蛋白”结构域（在哺乳动物SOCS1中，与E3泛素连接酶复合物相互作用）对于抑制DF-1细胞中细胞因子诱导的JAK/STAT信号激活不是必需的。SOCS1在DF-1细胞中的过表达导致IFN-β、MX1、IFIT5和MDA5在PBG98感染后的表达显著相对降低，病毒产量增加。相反，在ifn刺激的DF-1细胞中，SOCS1的敲低增加了ISG诱导并降低了病毒产量。我们的研究结果表明，像其哺乳动物对应物一样，ChSOCS1减少了IFN信号通路的诱导。
We conducted microarray analysis of the increasingly popular chicken DF-1 cell line and its primary progenitor, chicken embryo fibroblast cells (CEF), in both normal and stimulated conditions using recombinant chicken IFN-α and the CEF-adapted infectious bursal disease virus vaccine strain PBG98. We found that DF-1 cells have an attenuated innate immune response compared to CEF, and also that chicken SOCS1 (ChSOCS1), a negative regulator of cytokine signaling, is expressed at levels 13-fold higher in DF-1 cells than in CEF. We found that overexpressing ChSOCS1 in CEF reduced levels of phosphorylated STAT1 protein in response to viral infection but that its “SOCS box protein” domain (which, in mammalian SOCS1, interacts with an E3 ubiquitin ligase complex) is not essential for the inhibition of cytokine-induced JAK/STAT signaling activation in DF-1 cells. Overexpression of SOCS1 in DF-1 cells led to a significant relative decrease in expression of IFN-β, MX1, IFIT5 and MDA5 in response to PBG98 infection, and increased viral yield. Conversely, knockdown of SOCS1 increased ISG induction and reduced viral yield in IFN-stimulated DF-1 cells. Our results show that, like its mammalian counterpart, ChSOCS1 reduces induction of the IFN signaling pathway.