ArticlePLoS pathogens2021
Origin and evolution of the zinc finger antiviral protein.
Article in PLoS pathogens, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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Who cites it
43 citing papers in PubMed, 68 citations in OpenAlex.
- SPRY domains encode ubiquitin ligase specificity for ZAP and RIG-I.PLoS pathogens · 2026Article
- Small RNA-mediated regulation of cross-kingdom gene expression in sugar beet genotypes resistant and susceptible to rhizomania.The Journal of general virology · 2025Article
- KHNYN is a manganese-dependent endoribonuclease required for ZAP-mediated antiviral restriction.Nucleic acids research · 2025Article
- Codon Usage Bias Analysis of Citrus Leaf Blotch Virus.Viruses · 2025Article
- Mammalian antiviral proteins ZAP and KHNYN can independently restrict CpG-enriched avian viruses.PLoS biology · 2025Article
- West Nile virus vaccine candidates attenuated by dinucleotide enrichment are immunogenic and protective against lethal infection.PLoS pathogens · 2025Article
- Mammalian ZAP and KHNYN can independently restrict CpG-enriched avian viruses.bioRxiv : the preprint server for biology · 2025Article
- HIV-2 evades restriction by ZAP through adaptations in the U3 LTR region despite increased CpG levels.Nucleic acids research · 2025Article
- Impact of the Zinc Antiviral Protein on the Genomic Composition of RNA Viruses Infecting Vertebrates.Molecular biology and evolution · 2025Article
- Host ZAP activity correlates with the levels of CpG suppression in primate lentiviruses.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Modulation of host gene expression by the zinc finger antiviral protein.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Human Riboviruses: A Comprehensive Study.Journal of molecular evolution · 2025Review
- Zinc-finger PARP proteins ADP-ribosylate alphaviral proteins and are required for interferon-γ-mediated antiviral immunity.Science advances · 2025Article
- Functional anatomy of zinc finger antiviral protein complexes.Nature communications · 2024Article
- A minimal complex of KHNYN and zinc-finger antiviral protein binds and degrades single-stranded RNA.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Evolutionary analysis of ZAP and its cofactors identifies intrinsically disordered regions as central elements in host-pathogen interactions.Computational and structural biotechnology journal · 2024Article
- Endogenous ZAP is associated with altered Zika virus infection phenotype.Virology journal · 2024Article
- Antiviral Effects of Avian Interferon-Stimulated Genes.Animals : an open access journal from MDPI · 2024Review
- Dual Roles of Host Zinc Finger Proteins in Viral RNA Regulation: Decay or Stabilization.International journal of molecular sciences · 2024Review
- Depletion of CpG dinucleotides in bacterial genomes may represent an adaptation to high temperatures.NAR genomics and bioinformatics · 2024Article
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
The human zinc finger antiviral protein (ZAP) recognizes RNA by binding to CpG dinucleotides. Mammalian transcriptomes are CpG-poor, and ZAP may have evolved to exploit this feature to specifically target non-self viral RNA. Phylogenetic analyses reveal that ZAP and its paralogue PARP12 share an ancestral gene that arose prior to extensive eukaryote divergence, and the ZAP lineage diverged from the PARP12 lineage in tetrapods. Notably, the CpG content of modern eukaryote genomes varies widely, and ZAP-like genes arose subsequent to the emergence of CpG-suppression in vertebrates. Human PARP12 exhibited no antiviral activity against wild type and CpG-enriched HIV-1, but ZAP proteins from several tetrapods had antiviral activity when expressed in human cells. In some cases, ZAP antiviral activity required a TRIM25 protein from the same or related species, suggesting functional co-evolution of these genes. Indeed, a hypervariable sequence in the N-terminal domain of ZAP contributed to species-specific TRIM25 dependence in antiviral activity assays. Crosslinking immunoprecipitation coupled with RNA sequencing revealed that ZAP proteins from human, mouse, bat and alligator exhibit a high degree of CpG-specificity, while some avian ZAP proteins appear more promiscuous. Together, these data suggest that the CpG- rich RNA directed antiviral activity of ZAP-related proteins arose in tetrapods, subsequent to the onset of CpG suppression in certain eukaryote lineages, with subsequent species-specific adaptation of cofactor requirements and RNA target specificity.
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