{"title":"Targeted Restriction of Viral Gene Expression and Replication by the ZAP Antiviral System.","authors":"Mattia Ficarelli, Stuart J D Neil, Chad M Swanson","doi":"10.1146/annurev-virology-091919-104213","DOIUrl":null,"url":null,"abstract":"<p><p>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.</p>","PeriodicalId":48761,"journal":{"name":"Annual Review of Virology","volume":null,"pages":null},"PeriodicalIF":8.1000,"publicationDate":"2021-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"35","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Annual Review of Virology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1146/annurev-virology-091919-104213","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2021/6/15 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"VIROLOGY","Score":null,"Total":0}
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.
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.