{"doi":"10.1128/jvi.00872-22","title":"A Nuclear Export Signal in KHNYN Required for Its Antiviral Activity Evolved as ZAP Emerged in Tetrapods","abstract":"The interferon system is part of the innate immune response that inhibits viruses and other pathogens. This system emerged approximately 500 million years ago in early vertebrates. Since then, some genes have evolved to become antiviral interferon-stimulated genes (ISGs) while others evolved so their encoded protein could interact with proteins encoded by ISGs and contribute to their activity. However, this remains poorly characterized. ZAP is an ISG that arose during tetrapod evolution and inhibits viral replication. Because KHNYN interacts with ZAP and is required for its antiviral activity against retroviruses, we conducted an evolutionary analysis to determine how specific amino acids in KHNYN evolved after ZAP emerged. This identified a nuclear export signal that evolved in tetrapods and is required for KHNYN to traffic in the cell and interact with ZAP. Overall, specific residues in KHNYN evolved to allow it to act as a cofactor for ZAP antiviral activity.","journal":"Journal of Virology","year":2023,"id":360038,"datarank":0.3453877639491069,"base_score":2.302585092994046,"endowment":2.302585092994046,"self_citation_contribution":0.3453877639491069,"citation_network_contribution":0.0,"self_endowment_contribution":0.3453877639491069,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":9,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.957,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":679609,"name":"Mattia Ficarelli","orcid":"0000-0002-9380-132X","position":1,"is_corresponding":false},{"id":270783,"name":"Harry Wilson","orcid":"0000-0002-3185-1073","position":2,"is_corresponding":false},{"id":576033,"name":"Dorota Kmieć","orcid":"0000-0001-7302-6015","position":3,"is_corresponding":false},{"id":833065,"name":"Rebecca L Youle","orcid":"0000-0002-8309-8562","position":4,"is_corresponding":false},{"id":719592,"name":"Joseph J. Wanford","orcid":"0000-0002-8099-8696","position":5,"is_corresponding":false},{"id":833062,"name":"Helena Winstone","orcid":"0000-0003-1936-6638","position":6,"is_corresponding":false},{"id":245461,"name":"Charlotte Odendall","orcid":"0000-0002-8398-7669","position":7,"is_corresponding":false},{"id":709717,"name":"Ian A. Taylor","orcid":"0000-0002-6763-3852","position":8,"is_corresponding":false},{"id":270799,"name":"Stuart J. D. Neil","orcid":"0000-0003-3306-5831","position":9,"is_corresponding":false},{"id":679610,"name":"Chad M. Swanson","orcid":"0000-0002-6650-3634","position":10,"is_corresponding":false},{"id":679608,"name":"María José Lista","orcid":"0009-0009-5476-5547","position":0,"is_corresponding":true}],"reference_count":79,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T01:14:01.896928Z","pmid":"36633408","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}