Open AccessTargeted Restriction of Viral Gene Expression and Replication by the ZAP Antiviral System
Author(s) -
Mattia Ficarelli,
Stuart Neil,
Chad M. Swanson
Publication year - 2021
Publication title -
annual review of virology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.605
H-Index - 42
eISSN - 2327-0578
pISSN - 2327-056X
DOI - 10.1146/annurev-virology-091919-104213
Subject(s) - biology , exoribonuclease , viral replication , antiviral protein , rna , rna interference , translation (biology) , microbiology and biotechnology , gene expression , gene , virology , messenger rna , genetics , virus , rnase 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.