Constitutively elevated levels of SOCS1 suppress innate responses in DF-1 immortalised chicken fibroblast cells.
Constitutively elevated levels of SOCS1 suppress innate responses in DF-1 immortalised chicken fibroblast cells.
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DOI：
10.1038/s41598-017-17730-2
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发表时间：
2017-12-13
影响因子：
4.6
通讯作者：
Skinner MA
中科院分区：
文献类型：
--
作者：
Giotis ES;Ross CS;Robey RC;Nohturfft A;Goodbourn S;Skinner MA
自发永生化的DF-1细胞系正在迅速取代其祖细胞原代鸡胚成纤维细胞（CEF），用于研究禽流感等禽病毒，但尚未报道比较其先天免疫表型的综合研究。我们进行了DF-1和CEFs的微阵列分析，在正常和刺激条件下使用鸡干扰素-α（chIFN-α）和减毒的传染性法氏囊病病毒疫苗株PBG 98。我们发现DF-1与CEF相比具有减弱的先天反应。细胞因子信号传导抑制因子1（chSOCS 1）的基础表达水平，是哺乳动物细胞因子信号传导的负调节因子，DF-1中的表达水平比CEF高16倍。chSOCS 1“SOCS盒”结构域（在哺乳动物中，与E3泛素连接酶复合物相互作用）对于抑制DF-1中精氨酸诱导的JAK/STAT信号传导激活不是必需的。在chIFN-α刺激的DF-1中过表达SOCS 1导致干扰素刺激的基因（ISG; MX 1和IFIT 5）表达相对降低，并增加PBG 98感染后的病毒产量。相反，SOCS 1的敲除增强了ISG的诱导，并降低了chIFN-α刺激的DF-1中的病毒产量。因此，SOCS 1减少鸡细胞中IFN信号通路的诱导，并可增强病毒复制。
The spontaneously immortalised DF-1 cell line is rapidly replacing its progenitor primary chicken embryo fibroblasts (CEFs) for studies on avian viruses such as avian influenza but no comprehensive study has as yet been reported comparing their innate immunity phenotypes. We conducted microarray analyses of DF-1 and CEFs, under both normal and stimulated conditions using chicken interferon-α (chIFN-α) and the attenuated infectious bursal disease virus vaccine strain PBG98. We found that DF-1 have an attenuated innate response compared to CEFs. Basal expression levels of Suppressor of Cytokine Signalling 1 (chSOCS1), a negative regulator of cytokine signalling in mammals, are 16-fold higher in DF-1 than in CEFs. The chSOCS1 “SOCS box” domain (which in mammals, interacts with an E3 ubiquitin ligase complex) is not essential for the inhibition of cytokine-induced JAK/STAT signalling activation in DF-1. Overexpression of SOCS1 in chIFN-α-stimulated DF-1 led to a relative decrease in expression of interferon-stimulated genes (ISGs; MX1 and IFIT5) and increased viral yield in response to PBG98 infection. Conversely, knockdown of SOCS1 enhanced induction of ISGs and reduced viral yield in chIFN-α-stimulated DF-1. Consequently, SOCS1 reduces induction of the IFN signalling pathway in chicken cells and can potentiate virus replication.
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影响因子：
5.5
作者：
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通讯作者：
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影响因子：
5.3
作者：
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作者：
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DOI：
10.3390/v6041672
发表时间：
2014-04-11
期刊：
Viruses
影响因子：
--
作者：
Jordan I;Sandig V
通讯作者：
Sandig V
影响因子：
5.4
作者：
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通讯作者：
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