Discipline of Infectious Diseases and Immunology, Faculty of Medicine and Health, Charles Perkins Centre, University of Sydney, Camperdown, NSW, Australia.
School of Microbiology, University College Cork, Cork, Ireland.
Front Immunol. 2019 Dec 11;10:2751. doi: 10.3389/fimmu.2019.02751. eCollection 2019.
The critical role of interferons (IFNs) in mediating the innate immune response to cytomegalovirus (CMV) infection is well established. However, in recent years the functional importance of the IFN-independent antiviral response has become clearer. IFN-independent, IFN regulatory factor 3 (IRF3)-dependent interferon-stimulated gene (ISG) regulation in the context of CMV infection was first documented 20 years ago. Since then several IFN-independent, IRF3-dependent ISGs have been characterized and found to be among the most influential in the innate response to CMV. These include virus inhibitory protein, endoplasmic reticulum-associated IFN-inducible (viperin), ISG15, members of the interferon inducible protein with tetratricopeptide repeats (IFIT) family, interferon-inducible transmembrane (IFITM) proteins and myxovirus resistance proteins A and B (MxA, MxB). IRF3-independent, IFN-independent activation of canonically IFN-dependent signaling pathways has also been documented, such as IFN-independent biphasic activation of signal transducer and activator of transcription 1 (STAT1) during infection of monocytes, differential roles of mitochondrial and peroxisomal mitochondrial antiviral-signaling protein (MAVS), and the ability of human CMV (HCMV) immediate early protein 1 (IE1) protein to reroute IL-6 signaling and activation of STAT1 and its associated ISGs. This review examines the role of identified IFN-independent ISGs in the antiviral response to CMV and describes pathways of IFN-independent innate immune response induction by CMV.
干扰素 (IFNs) 在介导巨细胞病毒 (CMV) 感染的先天免疫反应中起着至关重要的作用，这一点已得到充分证实。然而，近年来，IFN 非依赖性抗病毒反应的功能重要性变得更加清晰。20 年前首次记录了 IFN 非依赖性、IRF3 依赖性干扰素刺激基因 (ISG) 调节在 CMV 感染背景下的作用。此后，已经鉴定了几种 IFN 非依赖性、IRF3 依赖性 ISGs，并发现它们在 CMV 先天反应中最具影响力。这些包括病毒抑制蛋白、内质网相关 IFN 诱导 (viperin)、ISG15、干扰素诱导蛋白具有四肽重复 (IFIT) 家族的成员、干扰素诱导跨膜 (IFITM) 蛋白和粘液病毒抗性蛋白 A 和 B (MxA、MxB)。IRF3 非依赖性、IFN 非依赖性激活经典 IFN 依赖性信号通路也已被记录，例如在单核细胞感染期间，转录激活因子 1 (STAT1) 的 IFN 非依赖性双相激活、线粒体和过氧化物酶体抗病毒信号蛋白 (MAVS) 的差异作用，以及人巨细胞病毒 (HCMV) 早期蛋白 1 (IE1) 蛋白重路由 IL-6 信号和 STAT1 及其相关 ISGs 的激活的能力。这篇综述考察了已鉴定的 IFN 非依赖性 ISGs 在 CMV 抗病毒反应中的作用，并描述了 CMV 诱导 IFN 非依赖性先天免疫反应的途径。
