TRIM Proteins in Host Defense and Viral Pathogenesis
TRIM Proteins in Host Defense and Viral Pathogenesis
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DOI：
10.1007/s40588-020-00150-8
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发表时间：
2020-08-08
影响因子：
5.2
通讯作者：
Rajsbaum, Ricardo
中科院分区：
文献类型：
--
作者：
Giraldo, Maria, I;Hage, Adam;Rajsbaum, Ricardo
TRIM （Tripartite motif）蛋白是一大类参与不同细胞功能的E3泛素连接酶。特别令人感兴趣的是它们在先天免疫、炎症和病毒复制中的作用。我们讨论了TRIM蛋白在病毒感染过程中导致致病性增加的新作用。TRIM蛋白调节不同的抗病毒和炎症信号通路，主要通过促进参与I型干扰素和nf - κ B通路的模式识别受体、衔接蛋白、激酶和转录因子等重要因子的泛素化。因此，病毒已经发展出针对TRIMs的免疫逃避机制。新的证据表明，病毒有能力直接利用TRIMs和泛素化过程来增强病毒的复制周期，从而增加发病机制。一份关于TRIM7的新报告也强调了TRIMs通过病毒蛋白泛素化的潜在前病毒作用，并提出了一种新的机制，即病毒包膜蛋白的泛素化可能是组织和物种向性的决定因素。TRIM蛋白在促进宿主防御病毒感染中具有重要功能；然而，病毒已经适应了逃避TRIMs介导的免疫反应，并可以劫持TRIMs最终增加病毒的发病机制。只有了解特定的TRIM-病毒相互作用并使用更多的体内方法，我们才能了解如何利用TRIM功能开发治疗方法来减少病毒的发病机制。
Purpose of Review Tripartite motif (TRIM) proteins are a large group of E3 ubiquitin ligases involved in different cellular functions. Of special interest are their roles in innate immunity, inflammation, and virus replication. We discuss novel roles of TRIM proteins during virus infections that lead to increased pathogenicity.Recent Findings TRIM proteins regulate different antiviral and inflammatory signaling pathways, mostly by promoting ubiquitination of important factors including pattern recognition receptors, adaptor proteins, kinases, and transcription factors that are involved in type I interferon and NF-kappa B pathways. Therefore, viruses have developed mechanisms to target TRIMs for immune evasion. New evidence is emerging indicating that viruses have the ability to directly use TRIMs and the ubiquitination process to enhance the viral replication cycle and cause increased pathogenesis. A new report on TRIM7 also highlights the potential pro-viral role of TRIMs via ubiquitination of viral proteins and suggests a novel mechanism by which ubiquitination of virus envelope protein may provide determinants of tissue and species tropism.Summary TRIM proteins have important functions in promoting host defense against virus infection; however, viruses have adapted to evade TRIM-mediated immune responses and can hijack TRIMs to ultimately increase virus pathogenesis. Only by understanding specific TRIM-virus interactions and by using more in vivo approaches can we learn how to harness TRIM function to develop therapeutic approaches to reduce virus pathogenesis.