Mouse superkiller-2-like helicase DDX60 is dispensable for type I IFN induction and immunity to multiple viruses.
Mouse superkiller-2-like helicase DDX60 is dispensable for type I IFN induction and immunity to multiple viruses.
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DOI：
10.1002/eji.201545794
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发表时间：
2015-12
影响因子：
5.4
通讯作者：
Reis e Sousa C
中科院分区：
文献类型：
--
作者：
Goubau D;van der Veen AG;Chakravarty P;Lin R;Rogers N;Rehwinkel J;Deddouche S;Rosewell I;Hiscott J;Reis e Sousa C
IFN-α/β通过诱导许多编码抗病毒防御效应物的基因的表达，使细胞能够对抗病毒感染。其中之一，Ski 2样DExH盒解旋酶DDX 60，最近被认为与人类细胞对丙型肝炎病毒的抗性有关，以及与通过视黄酸诱导基因1样受体（RLR）诱导IFN-α/β有关，视黄酸诱导基因1样受体（RLR）以细胞内在方式检测RNA病毒的存在。在这里，我们试图研究DDX 60在IFN-α/β诱导和抵抗病毒感染中的作用。对Ddx 60缺陷小鼠的成纤维细胞和骨髓细胞的分析显示，响应于RLR激动剂、RNA病毒或其他刺激，IFN-α/β的产生没有受损。此外，DDX 60的过表达不增强IFN诱导，并且DDX 60不与RLR相互作用或从病毒感染的细胞捕获RLR激动剂。我们也没有发现Ddx 60缺陷鼠细胞或小鼠对甲型流感病毒、脑心肌炎病毒、辛德毕斯病毒、牛痘病毒或单纯疱疹病毒1感染的抵抗力有任何损害。这些结果对DDX 60作为RLR反应的广泛作用正调节剂的报告作用提出了质疑，并暗示它可能作为特定病毒或一类病毒的高度特异性限制因子发挥作用。
IFN‐α/β allow cells to fight virus infection by inducing the expression of many genes that encode effectors of antiviral defense. One of these, the Ski2‐like DExH‐box helicase DDX60, was recently implicated in resistance of human cells to hepatitis C virus, as well as in induction of IFN‐α/β by retinoic acid inducible gene 1‐like receptors (RLRs) that detect the presence of RNA viruses in a cell‐intrinsic manner. Here, we sought to investigate the role of DDX60 in IFN‐α/β induction and in resistance to virus infection. Analysis of fibroblasts and myeloid cells from Ddx60‐deficient mice revealed no impairment in IFN‐α/β production in response to RLR agonists, RNA viruses, or other stimuli. Moreover, overexpression of DDX60 did not potentiate IFN induction and DDX60 did not interact with RLRs or capture RLR agonists from virally infected cells. We also failed to identify any impairment in Ddx60‐deficient murine cells or mice in resistance to infection with influenza A virus, encephalomyocarditis virus, Sindbis virus, vaccinia virus, or herpes simplex virus‐1. These results put in question the reported role of DDX60 as a broad‐acting positive regulator of RLR responses and hint at the possibility that it may function as a restriction factor highly specific for a particular virus or class of viruses.