4.3 Article Book Chapter

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

期刊

ANNUAL REVIEW OF VIROLOGY, VOL 8
卷 8, 期 -, 页码 265-283

出版社

ANNUAL REVIEWS
DOI: 10.1146/annurev-virology-091919-104213

关键词

ZAP; zinc finger antiviral protein; ZC3HAV1; PARP13; CpG dinucleotide; virus; interferon-stimulated gene

资金

  1. Medical Research Council [MR/S000844/1]
  2. European Union
  3. UK Medical Research Council [MR/R50225X/1]

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ZAP restricts the replication of a broad range of RNA and DNA viruses by directly binding viral RNA and targeting it for degradation. ZAP interacts with many cellular proteins, with only a few being essential for its antiviral activity.
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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