Targeted Restriction of Viral Gene Expression and Replication by the ZAP Antiviral System.

IF 8.1 1区 医学 Q1 VIROLOGY Annual Review of Virology Pub Date : 2021-09-29 Epub Date: 2021-06-15 DOI:10.1146/annurev-virology-091919-104213
Mattia Ficarelli, Stuart J D Neil, Chad M Swanson
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引用次数: 35

Abstract

The zinc finger antiviral protein (ZAP) restricts the replication of a broad range of RNA and DNA viruses. ZAP directly binds viral RNA, targeting it for degradation and inhibiting its translation. While the full scope of RNA determinants involved in mediating selective ZAP activity is unclear, ZAP binds CpG dinucleotides, dictating at least part of its target specificity. ZAP interacts with many cellular proteins, although only a few have been demonstrated to be essential for its antiviral activity, including the 3'-5' exoribonuclease exosome complex, TRIM25, and KHNYN. In addition to inhibiting viral gene expression, ZAP also directly and indirectly targets a subset of cellular messenger RNAs to regulate the innate immune response. Overall, ZAP protects a cell from viral infection by restricting viral replication and regulating cellular gene expression. Further understanding of the ZAP antiviral system may allow for novel viral vaccine and anticancer therapy development.

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ZAP抗病毒系统对病毒基因表达和复制的靶向限制。
锌指抗病毒蛋白(ZAP)限制了多种RNA和DNA病毒的复制。ZAP直接结合病毒RNA,靶向其降解并抑制其翻译。虽然介导选择性ZAP活性的RNA决定因素的全部范围尚不清楚,但ZAP结合CpG二核苷酸,至少部分决定了其目标特异性。ZAP与许多细胞蛋白相互作用,尽管只有少数已被证明对其抗病毒活性至关重要,包括3'-5'外核糖核酸酶外泌体复合物,TRIM25和KHNYN。除了抑制病毒基因表达外,ZAP还直接或间接地靶向细胞信使rna的一个子集来调节先天免疫反应。总的来说,ZAP通过限制病毒复制和调节细胞基因表达来保护细胞免受病毒感染。进一步了解ZAP抗病毒系统可能有助于开发新的病毒疫苗和抗癌疗法。
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来源期刊
CiteScore
19.40
自引率
0.90%
发文量
28
期刊介绍: The Annual Review of Virology serves as a conduit for disseminating thrilling advancements in our comprehension of viruses spanning animals, plants, bacteria, archaea, fungi, and protozoa. Its reviews illuminate novel concepts and trajectories in basic virology, elucidating viral disease mechanisms, exploring virus-host interactions, and scrutinizing cellular and immune responses to virus infection. These reviews underscore the exceptional capacity of viruses as potent probes for investigating cellular function.
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