Cheng Yuqiang, Liu Yunxia, Wang Yingying, Niu Qiaona, Gao Quanxin, Fu Qiang, Ma Jingjiao, Wang Hengan, Yan Yaxian, Ding Chan, Sun Jianhe
Shanghai Key Laboratory of Veterinary Biotechnology, Key Laboratory of Urban Agriculture (South), Ministry of Agriculture, School of Agriculture and Biology, Shanghai Jiao Tong University, Shanghai 200240, China.
Shanghai Zoo, 2381 Hongqiao Road, Shanghai 200335, China.
Dev Comp Immunol. 2017 Nov;76:334-342. doi: 10.1016/j.dci.2017.07.001. Epub 2017 Jul 3.
The recognition of pathogenic DNA is important to the initiation of antiviral responses. Here, we report the identification of the first avian DEAD (Asp-Glu-Ala-Asp) box polypeptide 41 (DDX41), an important DNA sensor, in chicken cells. In our study, we confirmed that chDDX41 is not an interferon-inducible gene. Knockdown of chDDX41 expression by shRNA blocked the ability of DF-1 cells to mount an IFN-β response to DNA and associated viruses. ChDDX41 mRNAs could be upregulated by double-stranded DNA (dsDNA) analogue poly(dA:dT), but not by double-stranded RNA (dsRNA) analogue poly(I:C). In poly(dA:dT) stimulation assays, the immune molecules involved in the DDX41-mediated IFN-β pathway in human cells were universally upregulated in chicken cells. Via coimmunoprecipitation (Co-IP) experiments, we found that chDDX41 could strongly interact with chicken stimulator of IFN genes (chSTING). Therefore, our results suggest that chDDX41 is involved in the dsDNA- and dsDNA virus-mediated chDDX41-chSTING-IFN-β signaling pathway in chicken cells.
识别致病DNA对抗病毒反应的启动至关重要。在此，我们报告了在鸡细胞中首次鉴定出重要的DNA传感器——禽源DEAD（天冬氨酸-谷氨酸-丙氨酸-天冬氨酸）框多肽41（DDX41）。在我们的研究中，我们证实chDDX41不是干扰素诱导基因。用shRNA敲低chDDX41的表达可阻断DF-1细胞对DNA及相关病毒产生IFN-β反应的能力。chDDX41 mRNA可被双链DNA（dsDNA）类似物聚（dA:dT）上调，但不能被双链RNA（dsRNA）类似物聚（I:C）上调。在聚（dA:dT）刺激试验中，人类细胞中参与DDX41介导的IFN-β途径的免疫分子在鸡细胞中普遍上调。通过免疫共沉淀（Co-IP）实验，我们发现chDDX41能与鸡干扰素基因刺激物（chSTING）强烈相互作用。因此，我们的结果表明chDDX41参与了鸡细胞中dsDNA和dsDNA病毒介导的chDDX41-chSTING-IFN-β信号通路。
