ISG15 driven cellular responses to virus infection.
ISG15 driven cellular responses to virus infection.
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DOI：
10.1042/bst20220839
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发表时间：
2022-12-16
影响因子：
3.9
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中科院分区：
文献类型：
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对感染的抗病毒反应的特征之一是产生干扰素，随后产生干扰素刺激基因。干扰素刺激基因15(ISG15)是最早和最丰富的干扰素信号诱导蛋白之一，在宿主免疫中具有多种功能。ISG15是一种类似泛素的修饰物，可以在类似泛素化的过程中连接到底物上，称为ISG化。游离的非结合形式既可以存在于细胞内，也可以分泌出来作为细胞因子发挥作用。有趣的是，据报道，ISG15在感染过程中对免疫病理学的发展既有利又不利。本文综述了在人类感染模型中ISG15在抗病毒反应中的作用的最新研究结果，重点介绍了自噬、炎症反应和细胞代谢以及病毒对抗它们的策略。ISG化领域的势头稳步增强；然而，之前在小鼠模型中进行的许多病毒感染研究与最近在人类细胞中的发现形成了鲜明对比，这突显了我们需要总结目前对其在人类中潜在抗病毒功能的理解，并确定需要在未来研究中解决的知识差距。
One of the hallmarks of antiviral responses to infection is the production of interferons and subsequently of interferon stimulated genes. Interferon stimulated gene 15 (ISG15) is among the earliest and most abundant proteins induced upon interferon signalling, encompassing versatile functions in host immunity. ISG15 is a ubiquitin like modifier that can be conjugated to substrates in a process analogous to ubiquitylation and referred to as ISGylation. The free unconjugated form can either exist intracellularly or be secreted to function as a cytokine. Interestingly, ISG15 has been reported to be both advantageous and detrimental to the development of immunopathology during infection. This review describes recent findings on the role of ISG15 in antiviral responses in human infection models, with a particular emphasis on autophagy, inflammatory responses and cellular metabolism combined with viral strategies of counteracting them. The field of ISGylation has steadily gained momentum; however much of the previous studies of virus infections conducted in mouse models are in sharp contrast with recent findings in human cells, underscoring the need to summarise our current understanding of its potential antiviral function in humans and identify knowledge gaps which need to be addressed in future studies.