{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T07:05:57Z","timestamp":1780383957271,"version":"3.54.1"},"update-to":[{"DOI":"10.1371\/journal.ppat.1009545","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2021,5,6]],"date-time":"2021-05-06T00:00:00Z","timestamp":1620259200000}}],"reference-count":38,"publisher":"Public Library of Science (PLoS)","issue":"4","license":[{"start":{"date-parts":[[2021,4,26]],"date-time":"2021-04-26T00:00:00Z","timestamp":1619395200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["U54 AI150470"],"award-info":[{"award-number":["U54 AI150470"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["R01AI50111"],"award-info":[{"award-number":["R01AI50111"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>\n                    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\n                    <jats:italic>ZAP<\/jats:italic>\n                    and its paralogue\n                    <jats:italic>PARP12<\/jats:italic>\n                    share an ancestral gene that arose prior to extensive eukaryote divergence, and the\n                    <jats:italic>ZAP<\/jats:italic>\n                    lineage diverged from the\n                    <jats:italic>PARP12<\/jats:italic>\n                    lineage in tetrapods. Notably, the CpG content of modern eukaryote genomes varies widely, and\n                    <jats:italic>ZAP<\/jats:italic>\n                    -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.\n                  <\/jats:p>","DOI":"10.1371\/journal.ppat.1009545","type":"journal-article","created":{"date-parts":[[2021,4,26]],"date-time":"2021-04-26T15:50:47Z","timestamp":1619452247000},"page":"e1009545","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":69,"title":["Origin and evolution of the zinc finger antiviral protein"],"prefix":"10.1371","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9333-1540","authenticated-orcid":true,"given":"Daniel","family":"Gon\u00e7alves-Carneiro","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew A.","family":"Takata","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9651-3892","authenticated-orcid":true,"given":"Heley","family":"Ong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9083-8696","authenticated-orcid":true,"given":"Amanda","family":"Shilton","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2368-3719","authenticated-orcid":true,"given":"Paul D.","family":"Bieniasz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2021,4,26]]},"reference":[{"issue":"1","key":"ppat.1009545.ref001","doi-asserted-by":"crossref","first-page":"667","DOI":"10.1146\/annurev-immunol-042617-053309","article-title":"RIG-I and Other RNA Sensors in Antiviral Immunity","volume":"36","author":"KT Chow","year":"2018","journal-title":"Annu Rev Immunol"},{"issue":"1","key":"ppat.1009545.ref002","doi-asserted-by":"crossref","first-page":"567","DOI":"10.1146\/annurev-virology-092818-015756","article-title":"Interferon-Stimulated Genes: What Do They All Do?","volume":"6","author":"JW Schoggins","year":"2019","journal-title":"Annu Rev Virol"},{"issue":"6","key":"ppat.1009545.ref003","doi-asserted-by":"crossref","first-page":"286","DOI":"10.1016\/j.tim.2011.03.006","article-title":"Two-stepping through time: mammals and viruses","volume":"19","author":"NR Meyerson","year":"2011","journal-title":"Trends Microbiol"},{"issue":"5587","key":"ppat.1009545.ref004","doi-asserted-by":"crossref","first-page":"1703 LP","DOI":"10.1126\/science.1074276","article-title":"Inhibition of Retroviral RNA Production by ZAP, a CCCH-Type Zinc Finger Protein","volume":"297","author":"G Gao","year":"2002","journal-title":"Science (80-)"},{"issue":"23","key":"ppat.1009545.ref005","doi-asserted-by":"crossref","first-page":"12781 LP","DOI":"10.1128\/JVI.78.23.12781-12787.2004","article-title":"The Zinc Finger Antiviral Protein Directly Binds to Specific Viral mRNAs through the CCCH Zinc Finger Motifs","volume":"78","author":"X Guo","year":"2004","journal-title":"J Virol"},{"issue":"5","key":"ppat.1009545.ref006","doi-asserted-by":"crossref","first-page":"2391 LP","DOI":"10.1128\/JVI.01601-06","article-title":"Inhibition of Filovirus Replication by the Zinc Finger Antiviral Protein","volume":"81","author":"S M\u00fcller","year":"2007","journal-title":"J Virol"},{"issue":"1","key":"ppat.1009545.ref007","doi-asserted-by":"crossref","first-page":"e1006145","DOI":"10.1371\/journal.ppat.1006145","article-title":"TRIM25 Enhances the Antiviral Action of Zinc-Finger Antiviral Protein (ZAP)","volume":"13","author":"MMH Li","year":"2017","journal-title":"PLOS Pathog"},{"issue":"9","key":"ppat.1009545.ref008","doi-asserted-by":"crossref","first-page":"e00088","DOI":"10.1128\/JVI.00088-17","article-title":"TRIM25 Is Required for the Antiviral Activity of Zinc Finger Antiviral Protein. 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