Targeted Restriction of Viral Gene Expression and Replication by the ZAP Antiviral System
Targeted Restriction of Viral Gene Expression and Replication by the ZAP Antiviral System
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DOI：
10.1146/annurev-virology-091919-104213
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发表时间：
2021-01-01
期刊：
影响因子：
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通讯作者：
Swanson, Chad M.
中科院分区：
文献类型：
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作者：
Ficarelli, Mattia;Neil, Stuart J. D.;Swanson, Chad M.
锌指抗病毒蛋白（ZAP）限制了广泛的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。虽然参与介导选择性ZAP活性的RNA决定簇的全部范围尚不清楚，但ZAP结合CpG二核苷酸，决定了其靶特异性的至少一部分。ZAP与许多细胞蛋白相互作用，尽管只有少数已被证明是其抗病毒活性所必需的，包括3 '-5'核糖核酸外切酶外泌体复合物、TRIM 25和KHNYN。除了抑制病毒基因表达外，ZAP还直接和间接靶向细胞信使RNA的子集以调节先天免疫应答。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。对ZAP抗病毒系统的进一步了解可能有助于开发新的病毒疫苗和抗癌治疗。
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.