Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
J Innate Immun. 2009;1(5):397-404. doi: 10.1159/000226245.
The host innate immune response, including the production of type-I IFN, represents the primary line of defense against invading viral pathogens. Of the hundreds of IFN-stimulated genes (ISGs) discovered to date, ISG15 was one of the first identified and shown to encode a ubiquitin-like protein that functions, in part, as a modifier of protein function. Evidence implicating ISG15 as an innate immune protein with broad-spectrum antiviral activity continues to accumulate rapidly. This review will summarize recent findings on the innate antiviral activity of ISG15, with a focus on the interplay between ubiquitination and ISGylation pathways resulting in modulation of RNA virus assembly/budding. Indeed, ubiquitination is known to be proviral for some RNA viruses, whereas the parallel ISGylation pathway is known to be antiviral. A better understanding of the antiviral activities of ISG15 will enhance our fundamental knowledge of host innate responses to viral pathogens and may provide insight useful for the development of novel therapeutic approaches designed to enhance the immune response against such pathogens.
宿主固有免疫反应，包括 I 型干扰素的产生，是抵御入侵病毒病原体的第一道防线。在迄今为止发现的数百种干扰素刺激基因 (ISGs) 中，ISG15 是最早被发现并被证明编码一种泛素样蛋白的基因之一，该蛋白的部分功能是作为蛋白质功能的调节剂。越来越多的证据表明，ISG15 是一种具有广谱抗病毒活性的固有免疫蛋白。本文将综述 ISG15 的固有抗病毒活性的最新发现，重点关注泛素化和 ISG 化途径之间的相互作用，导致 RNA 病毒组装/出芽的调节。事实上，已知泛素化对某些 RNA 病毒是有利的，而平行的 ISG 化途径是抗病毒的。更好地了解 ISG15 的抗病毒活性将增强我们对宿主固有免疫反应的基本认识对病毒病原体，并可能为开发旨在增强针对此类病原体的免疫反应的新型治疗方法提供有用的见解。
