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

Mattia Ficarelli; Stuart J.D. Neil; Chad M. Swanson

doi:10.1146/annurev-virology-091919-104213

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

Mattia Ficarelli, Stuart J.D. Neil, Chad M. Swanson^*

^*Corresponding author for this work

Infectious Diseases

Research output: Contribution to journal › Article › peer-review

43 Citations (Scopus)

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 prime -5 prime 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.

Original language	English
Pages (from-to)	265-283
Number of pages	19
Journal	Annual Review of Virology
Volume	8
Issue number	1
DOIs	https://doi.org/10.1146/annurev-virology-091919-104213
Publication status	Published - 29 Sept 2021

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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 prime -5 prime 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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Targeted Restriction of Viral Gene Expression and Replication by the ZAP Antiviral System

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