DDX58/IFIH1介导的干扰素α/β诱导
中文名称
通路描述
RIG-I样核酸内切酶（RLHs）是核糖核酸诱导基因-I（RIG-I，DDX58）和黑色素瘤分化相关基因5（MDA5，IFIH1）的RNA核酸内切酶，它们识别存在于细胞质中的病毒双链RNA（dsRNA）。(Yoneyama M & Fujita T 2007, 2008)。在病毒感染期间，正链RNA病毒家族（如黄病毒科和冠状病毒科）会产生dsRNA，而负链RNA病毒家族（如副粘病毒科和副黏病毒科）和DNA病毒家族（如疱疹病毒科和腺病毒科）也会产生dsRNA (Weber F et al. 2006; Son KN et al. 2015)。功能上，RIG-I（DDX58）和MDA5（IFIH1）以相似的方式正调控IFN基因，但它们对不同病毒物种的反应不同。DDX58（RIG-I）对于检测流感病毒、仙台病毒、VSV和日本脑炎病毒（JEV）是必需的，而IFIH1（MDA5）对于感知脑脊髓炎病毒（EMCV）、Mengo病毒和Theiler病毒是必需的，这些病毒都属于正链RNA病毒科。RIG-I和MDA5信号导致IKKε和（TKK结合激酶1）TBK1的激活，这两种丝氨酸/苏氨酸激酶磷酸化干扰素调节因子3和7（IRF3和IRF7）。在磷酸化后，IRF3和IRF7转位到细胞核内，随后诱导干扰素α（IFNA）和干扰素β（IFNB）基因转录 (Yoneyama M et al. 2004; Yoneyama M & Fujita T 2007, 2008)。
英文描述
DDX58/IFIH1-mediated induction of interferon-alpha/beta RIG-I-like helicases (RLHs) the retinoic acid inducible gene-I (RIG-I, DDX58) and melanoma differentiation associated gene 5 (MDA5, IFIH1) are RNA helicases that recognize viral double-stranded RNA (dsRNA) present within the cytoplasm (Yoneyama M & Fujita T 2007, 2008). Upon viral infection dsRNA is generated by positive-strand RNA virus families such as Flaviviridae and Coronaviridae, negative-strand RNA virus families including Orthomyxoviridae and Paramyxoviridae, and DNA virus families such as Herpesviridae and Adenoviridae (Weber F et al. 2006; Son KN et al. 2015). Functionally RIG-I (DDX58) and MDA5 (IFIH1) positively regulate the IFN genes in a similar fashion, however they differ in their response to different viral species. DDX58 (RIG-I) is essential for detecting influenza virus, Sendai virus, VSV and Japanese encephalitis virus (JEV), whereas IFIH1 (MDA5) is essential in sensing encephalomyocarditis virus (EMCV), Mengo virus and Theiler's virus, all of which belong to the picornavirus family. RIG-I and MDA5 signalling results in the activation of IKK epsilon and (TKK binding kinase 1) TBK1, two serine/threonine kinases that phosphorylate interferon regulatory factor 3 and 7 (IRF3 and IRF7). Upon phosphorylation, IRF3 and IRF7 translocate to the nucleus and subsequently induce interferon alpha (IFNA) and interferon beta (IFNB) gene transcription (Yoneyama M et al. 2004; Yoneyama M & Fujita T 2007, 2008).
所含基因
23 个基因