PDF(Pubmed)
Abstract：
Several viruses are now known to code for deubiquitinating proteases in their genomes. Ubiquitination is an essential post-translational modification of cellular substrates involved in many processes in the cell, including in innate immune signalling. This post-translational modification is regulated by the ubiquitin conjugation machinery, as well as various host deubiquitinating enzymes. The conjugation of ubiquitin chains to several innate immune related factors is often needed to induce downstream signalling, shaping the antiviral response. Viral deubiquitinating proteins, besides often having a primary function in the viral replication cycle by cleaving the viral polyprotein, are also able to cleave ubiquitin chains from such host substrates, in that way exerting a function in innate immune evasion. The presence of viral deubiquitinating enzymes has been firmly established for numerous animal-infecting viruses, such as some well-researched and clinically important nidoviruses, and their presence has now been confirmed in several plant viruses as well. Viral proteases in general have long been highlighted as promising drug targets, with a current focus on small molecule inhibitors. In this review, we will discuss the range of viral deubiquitinating proteases known to date, summarise the various avenues explored to inhibit such proteases and discuss novel strategies and models intended to inhibit and study these specific viral enzymes.
摘要：
现在已知几种病毒在其基因组中编码去泛素化蛋白酶。泛素化是细胞底物的重要翻译后修饰，参与细胞中的许多过程，包括先天免疫信号。这种翻译后修饰受泛素缀合机制的调节，以及各种宿主去泛素化酶。泛素链与几种先天免疫相关因子的结合通常需要诱导下游信号传导。塑造抗病毒反应。病毒去泛素蛋白，除了通常通过切割病毒多蛋白在病毒复制周期中具有主要功能外，还能够从这些宿主底物上切割泛素链，以这种方式发挥先天免疫逃避的功能。病毒去泛素化酶的存在已经在许多动物感染病毒中得到了证实，例如一些经过充分研究和临床上重要的病毒，现在已经在几种植物病毒中证实了它们的存在。一般来说，病毒蛋白酶一直被强调为有前途的药物靶标。目前专注于小分子抑制剂。在这次审查中,我们将讨论迄今为止已知的病毒去泛素化蛋白酶的范围，总结探索的各种途径来抑制这些蛋白酶，并讨论旨在抑制和研究这些特定病毒酶的新策略和模型。
