{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T21:33:19Z","timestamp":1791408799087,"version":"4.3.3"},"reference-count":54,"publisher":"Public Library of Science (PLoS)","issue":"12","license":[{"start":{"date-parts":[[2024,12,17]],"date-time":"2024-12-17T00:00:00Z","timestamp":1734393600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"the National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["32192454"],"award-info":[{"award-number":["32192454"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"name":"the National Key Research and Development Programs of China","award":["2021YFD1801102"],"award-info":[{"award-number":["2021YFD1801102"]}]},{"name":"the Fundamental Research Funds for the Central Universities","award":["2022-KYY-517101-0005"],"award-info":[{"award-number":["2022-KYY-517101-0005"]}]},{"name":"Hangzhou Chengxi Sci-tech innovation Corridor Management Committee"}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>Circular RNAs (circRNAs) exert diverse biological functions in different processes. However, the role of circRNAs during virus infection is mostly unknown. Herein, we explored the characteristics of host circRNAs using alphaherpesvirus pseudorabies virus (PRV) as a model. PRV infection upregulated the expression of circRNA circ29164, which does not encode a protein. RNA pulldown assays identified that circ29164 interacts with the microRNA ssc-miRNA-24-3p. Further analysis indicated that ssc-miR-24-3p targets the mRNA encoding kelch-like ECH-associated protein 1 (KEAP1), and circ29164 competitively binds to ssc-miR-24-3p to prevent it binding to <jats:italic>Keap1<\/jats:italic>. Apoptosis detection demonstrated that circ29164 or <jats:italic>Keap1<\/jats:italic> overexpression, but not knockdown, induced caspase 3 activity and the release of cytochrome C from mitochondria, and inhibited PRV replication. Taken together, these data identified a previously undiscovered circRNA, circ29164, which inhibits PRV replication by competitively binding to ssc-24-3p to maintain KEAP1 levels.<\/jats:p>","DOI":"10.1371\/journal.ppat.1012712","type":"journal-article","created":{"date-parts":[[2024,12,17]],"date-time":"2024-12-17T18:40:09Z","timestamp":1734460809000},"page":"e1012712","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":8,"title":["A previously unidentified circRNA inhibits virus replication by regulating the miR-24-3p\/KEAP1 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apoptotic program in cell-free extracts: requirement for dATP and cytochrome c","volume":"86","author":"X Liu","year":"1996","journal-title":"CELL"},{"issue":"6","key":"ppat.1012712.ref027","doi-asserted-by":"crossref","first-page":"516","DOI":"10.1038\/sj.cdd.4400527","article-title":"Apoptosis inducing factor (AIF): a phylogenetically old, caspase-independent effector of cell death.","volume":"6","author":"HK Lorenzo","year":"1999","journal-title":"CELL DEATH DIFFER"},{"issue":"2","key":"ppat.1012712.ref028","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1016\/S1097-2765(02)00442-2","article-title":"Three-dimensional structure of the apoptosome: implications for assembly, procaspase-9 binding, and activation","volume":"9","author":"D Acehan","year":"2002","journal-title":"MOL CELL"},{"issue":"3","key":"ppat.1012712.ref029","doi-asserted-by":"crossref","first-page":"304","DOI":"10.1093\/jnci\/djx166","article-title":"Novel Role of FBXW7 Circular RNA in Repressing Glioma 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