Section of Virology, School of Medicine, St Mary's Campus, Imperial College London, London, W2 1PG, UK.
Institute for Infection and Immunity, St George's, University of London, London, SW17 0RE, UK.
Sci Rep. 2017 Dec 13;7(1):17485. doi: 10.1038/s41598-017-17730-2.
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.
自发永生化的 DF-1 细胞系正在迅速取代其原代鸡胚成纤维细胞（CEF），用于研究禽流感病毒，如禽流感，但迄今为止尚未有比较它们先天免疫表型的综合研究报告。我们使用鸡干扰素-α（chIFN-α）和减毒传染性法氏囊病病毒疫苗株 PBG98，对 DF-1 和 CEF 进行了正常和刺激条件下的微阵列分析。我们发现，DF-1 的先天反应较 CEF 减弱。细胞因子信号抑制物 1（chSOCS1）的基础表达水平，在哺乳动物中是细胞因子信号的负调节剂，在 DF-1 中的表达水平比 CEF 高 16 倍。在 DF-1 中，SOCS1 的 chSOCS1“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）对于抑制细胞因子诱导的 JAK/STAT 信号激活不是必需的。在 chIFN-α 刺激的 DF-1 中转染 SOCS1 过表达，导致干扰素刺激基因（ISGs；MX1 和 IFIT5）的表达相对减少，并且对 PBG98 感染的病毒产量增加。相反，SOCS1 的敲低增强了 chIFN-α 刺激的 DF-1 中 ISGs 的诱导，并降低了病毒产量。因此，SOCS1 降低了鸡细胞中 IFN 信号通路的诱导，并可能增强病毒复制。
