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干扰素刺激基因:新平台与计算方法

Interferon-stimulated genes: new platforms and computational approaches.

作者信息

Green Richard, Ireton Reneé C, Gale Michael

机构信息

Department of Immunology and the Center for Innate Immunity and Immune Disease (CIIID), University of Washington, Seattle, WA, USA.

出版信息

Mamm Genome. 2018 Aug;29(7-8):593-602. doi: 10.1007/s00335-018-9755-6. Epub 2018 Jul 7.

Abstract

Interferon-stimulated genes (ISGs) are the effectors of interferon (IFN) actions and play major roles in innate immune defense against microbial infection. During virus infection, ISGs impart antiviral actions to control virus replication and spread but can also contribute to disease pathology if their expression is unchecked. Antiviral ISGs have been identified by a variety of biochemical, genetic, and virologic methods. New computational approaches are expanding and redefining ISGs as responders to a variety of stimuli beyond IFNs, including virus infection, stress, and other events that induce cytokines. These studies reveal that the expression of ISG subsets link to interferon regulatory factors (IRF)s, NF-kB, and other transcription factors that impart gene expression in specific cell types independently of IFNs, including stem cells and other cell types where ISGs are constitutively expressed. Here, we provide a broad overview of ISGs, define virus-induced genes (VSG)s, and discuss the application of computational approaches and bioinformatics platforms to evaluate the functional role of ISGs in epigenetics, immune programming, and vaccine responses.

摘要

干扰素刺激基因(ISGs)是干扰素(IFN)作用的效应器,在针对微生物感染的固有免疫防御中发挥主要作用。在病毒感染期间,ISGs发挥抗病毒作用以控制病毒复制和传播,但如果其表达不受控制,也可能导致疾病病理变化。抗病毒ISGs已通过多种生化、遗传和病毒学方法得以鉴定。新的计算方法正在扩展并重新定义ISGs,将其视为对包括病毒感染、应激和其他诱导细胞因子的事件在内的多种IFN以外刺激的反应者。这些研究表明,ISG亚群的表达与干扰素调节因子(IRF)、核因子-κB(NF-κB)以及其他转录因子相关,这些转录因子在特定细胞类型中独立于IFN赋予基因表达,包括干细胞和其他组成性表达ISGs的细胞类型。在此,我们对ISGs进行广泛概述,定义病毒诱导基因(VSG),并讨论计算方法和生物信息学平台在评估ISGs在表观遗传学、免疫编程和疫苗反应中的功能作用方面的应用。

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