Fensterl Volker, Sen Ganes C
Department of Molecular Genetics, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, Ohio, USA.
Department of Molecular Genetics, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, Ohio, USA
J Virol. 2015 Mar;89(5):2462-8. doi: 10.1128/JVI.02744-14. Epub 2014 Nov 26.
A major component of the protective antiviral host defense is contributed by the intracellular actions of the proteins encoded by interferon-stimulated genes (ISGs); among these are the interferon-induced proteins with tetratricopeptide repeats (IFITs), consisting of four members in human and three in mouse. IFIT proteins do not have any known enzyme activity. Instead, they inhibit virus replication by binding and regulating the functions of cellular and viral proteins and RNAs. Although all IFITs are comprised of multiple copies of the degenerate tetratricopeptide repeats, their distinct tertiary structures enable them to bind different partners and affect host-virus interactions differently. The recent use of Ifit knockout mouse models has revealed novel antiviral functions of these proteins and new insights into the specificities of ISG actions. This article focuses on human and murine IFIT1 and IFIT2 by reviewing their mechanisms of action, their critical roles in protecting mice from viral pathogenesis, and viral strategies to evade IFIT action.
保护性抗病毒宿主防御的一个主要组成部分是由干扰素刺激基因（ISG）编码的蛋白质的细胞内作用所贡献的；其中包括具有四肽重复序列的干扰素诱导蛋白（IFIT），人类中有四个成员，小鼠中有三个成员。IFIT蛋白没有任何已知的酶活性。相反，它们通过结合和调节细胞和病毒蛋白及RNA的功能来抑制病毒复制。尽管所有IFIT都由多个简并四肽重复序列组成，但其独特的三级结构使它们能够结合不同的伙伴，并以不同方式影响宿主与病毒的相互作用。最近使用Ifit基因敲除小鼠模型揭示了这些蛋白质的新抗病毒功能以及对ISG作用特异性的新见解。本文通过综述人类和小鼠IFIT1及IFIT2的作用机制、它们在保护小鼠免受病毒发病机制影响方面的关键作用以及病毒逃避IFIT作用的策略，重点关注这两种蛋白。
