Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.
Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.
Viruses. 2010 Oct;2(10):2154-2168. doi: 10.3390/v2102154. Epub 2010 Sep 28.
The type I interferon system plays a critical role in limiting the spread of viral infection. Viruses induce the production of interferon (IFN), which after binding to the IFN-α/β receptor (IFNAR), and triggering of the JAK/STAT signaling cascade, results in the induction of interferon-stimulated genes (ISGs). These ISGs function to inhibit viral replication and to regulate the host immune response. Among these ISGs, the ubiquitin-like molecule, ISG15, is one of the most strongly induced proteins. Similar to ubiquitin, through an IFN induced conjugation cascade, ISG15 is covalently linked to a variety of cellular proteins, suggesting regulation of different cellular processes. Studies performed over the past several years have shown that ISG15 plays a central role in the host's antiviral response against many viruses. Mice lacking ISG15 display increased susceptibility to multiple viruses. Furthermore, several viruses have developed immune evasion strategies that directly target the ISG15 pathway. Work is now underway to determine the mechanism by which ISG15 functions as an antiviral molecule, such that therapies targeting this pathway can be developed in the future.
I 型干扰素系统在限制病毒感染的传播中起着至关重要的作用。病毒诱导干扰素（IFN）的产生，IFN 与 IFN-α/β 受体（IFNAR）结合，并触发 JAK/STAT 信号级联反应，导致干扰素刺激基因（ISGs）的诱导。这些 ISGs 可抑制病毒复制并调节宿主免疫反应。在这些 ISGs 中，泛素样分子 ISG15 是诱导最强烈的蛋白之一。与泛素相似，通过 IFN 诱导的缀合级联反应，ISG15 与多种细胞蛋白共价连接，表明对不同细胞过程的调节。过去几年的研究表明，ISG15 在宿主对多种病毒的抗病毒反应中起着核心作用。缺乏 ISG15 的小鼠对多种病毒的敏感性增加。此外，一些病毒已经开发出针对 ISG15 途径的免疫逃避策略。目前正在努力确定 ISG15 作为抗病毒分子的作用机制，以便将来可以开发针对该途径的治疗方法。
