{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T06:16:52Z","timestamp":1783577812514,"version":"3.55.0"},"reference-count":42,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T00:00:00Z","timestamp":1783555200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Circular RNAs (circRNAs) are covalently closed endogenous RNAs that regulate gene expression at the post transcriptional level and have been implicated in antiviral immunity. However, their functional roles and regulatory mechanisms during influenza A virus (IAV) infection remain incompletely defined.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>circZFYVE1 expression was profiled in A549 cells infected with the WSN strain of IAV using RT qPCR under time course and dose response conditions. The mechanistic function of circZFYVE1 was investigated through miRNA target prediction, luciferase reporter assays, and functional assays assessing its role as a competing endogenous RNA (ceRNA) and its impact on innate antiviral signaling.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>circZFYVE1 expression was induced in a time  and dose dependent manner following WSN infection. Mechanistically, circZFYVE1 acts as a ceRNA by sponging hsa miR 4435, thereby relieving miRNA mediated suppression of the processing body associated protein LSM14A and enhancing innate antiviral signaling during infection.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>These findings define a circRNA\u2013miRNA\u2013mRNA regulatory axis that links IAV infection to innate antiviral responses, providing new insights into circRNA mediated host defenses. The circZFYVE1\/LSM14A pathway represents a potential target for future studies aimed at modulating endogenous antiviral immunity.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1841925","type":"journal-article","created":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T05:36:18Z","timestamp":1783575378000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["CircZFYVE1 functions as a competitive endogenous RNA to enhance LSM14A-mediated antiviral defense against influenza A virus"],"prefix":"10.3389","volume":"17","author":[{"given":"Bingchen","family":"Qiao","sequence":"first","affiliation":[{"name":"Ministry of Education (MOE) Joint International Research Laboratory of Animal Health and Food Safety, Engineering Center of Animal Immunity of Jiangsu Province, College of Veterinary Medicine, Nanjing Agricultural University","place":["Nanjing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiqing","family":"Zheng","sequence":"additional","affiliation":[{"name":"Ministry of Education (MOE) Joint International Research Laboratory of Animal Health and Food Safety, Engineering Center of Animal Immunity of Jiangsu Province, College of Veterinary Medicine, Nanjing Agricultural University","place":["Nanjing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoting","family":"Zhang","sequence":"additional","affiliation":[{"name":"Ministry of Education (MOE) Joint International Research Laboratory of Animal Health and Food Safety, Engineering Center of Animal Immunity of Jiangsu Province, College of Veterinary Medicine, Nanjing Agricultural University","place":["Nanjing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Menglu","family":"Fan","sequence":"additional","affiliation":[{"name":"Ministry of Education (MOE) Joint International Research Laboratory of Animal Health and Food Safety, Engineering Center of Animal Immunity of Jiangsu Province, College of Veterinary Medicine, Nanjing Agricultural University","place":["Nanjing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiyuan","family":"Liu","sequence":"additional","affiliation":[{"name":"Ministry of Education (MOE) Joint International Research Laboratory of Animal Health and Food Safety, Engineering Center of Animal Immunity of Jiangsu Province, College of Veterinary Medicine, Nanjing Agricultural University","place":["Nanjing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linjuan","family":"Wu","sequence":"additional","affiliation":[{"name":"Ministry of Education (MOE) Joint International Research Laboratory of Animal Health and Food Safety, Engineering Center of Animal Immunity of Jiangsu Province, College of Veterinary Medicine, Nanjing Agricultural University","place":["Nanjing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan","family":"Su","sequence":"additional","affiliation":[{"name":"Ministry of Education (MOE) Joint International Research Laboratory of Animal Health and Food Safety, Engineering Center of Animal Immunity of Jiangsu Province, College of Veterinary Medicine, Nanjing Agricultural University","place":["Nanjing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jihui","family":"Ping","sequence":"additional","affiliation":[{"name":"Ministry of Education (MOE) Joint International Research Laboratory of Animal Health and Food Safety, Engineering Center of Animal Immunity of Jiangsu Province, College of Veterinary Medicine, Nanjing Agricultural University","place":["Nanjing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,7,9]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a038356","article-title":"Human influenza epidemiology","volume":"11","author":"Ryu","year":"2021","journal-title":"Cold Spring Harb Perspect Med"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1240532","article-title":"H7N9 influenza viruses are transmissible in ferrets by respiratory droplet","volume":"341","author":"Zhang","year":"2013","journal-title":"Science"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1080\/22221751.2024.2343912","article-title":"Evolution of H7N9 highly pathogenic avian influenza virus in the context of vaccination","volume":"13","author":"Hou","year":"2024","journal-title":"Emerg Microbes Infect"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1080\/22221751.2025.2509748","article-title":"Characterization of emerging H3N3 avian influenza viruses in poultry in China","volume":"14","author":"Yan","year":"2025","journal-title":"Emerg Microbes Infect"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1261\/rna.047126.114","article-title":"Circular RNAs: diversity of form and function","volume":"20","author":"Lasda","year":"2014","journal-title":"Rna"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2021.742984","article-title":"Functional roles of non-coding RNAs in the interaction between host and influenza A virus","volume":"12","author":"Sajjad","year":"2021","journal-title":"Front Microbiol"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1016\/j.omtn.2021.05.022","article-title":"Recent research progress on circular RNAs: biogenesis, properties, functions, and therapeutic potential","volume":"25","author":"Sharma","year":"2021","journal-title":"Mol Ther Nucleic Acids"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2022.04.021","article-title":"Circular RNAs: characterization, cellular roles, and applications","volume":"185","author":"Liu","year":"2022","journal-title":"Cell"},{"key":"B9","doi-asserted-by":"publisher","first-page":"84","DOI":"10.1016\/j.jconrel.2022.05.043","article-title":"Circular RNA: an emerging frontier in RNA therapeutic targets, RNA therapeutics, and mRNA vaccines","volume":"348","author":"Liu","year":"2022","journal-title":"J Ctrl Release"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.2890","article-title":"Detecting and characterizing circular RNAs","volume":"32","author":"Jeck","year":"2014","journal-title":"Nat Biotechnol"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2019.04.020","article-title":"Circle the wagons: circular RNAs control innate immunity","volume":"177","author":"Wilusz","year":"2019","journal-title":"Cell"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1016\/j.tibs.2020.08.006","article-title":"Circular RNAs in immune response and viral infection","volume":"45","author":"Yan","year":"2020","journal-title":"Trends Biochem Sci"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2023.106946","article-title":"CircRNA in ocular neovascular diseases: fundamental mechanism and clinical potential","volume":"197","author":"Zhang","year":"2023","journal-title":"Pharmacol Res"},{"key":"B14","doi-asserted-by":"publisher","first-page":"597","DOI":"10.1038\/s41568-024-00721-7","article-title":"Circular RNA in cancer","volume":"24","author":"Conn","year":"2024","journal-title":"Nat Rev Cancer"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1009438","article-title":"Circular RNA circDtx1 regulates IRF3-mediated antiviral immune responses through suppression of miR-15a-5p-dependent TRIF downregulation in teleost fish","volume":"17","author":"Zheng","year":"2021","journal-title":"PloS Pathog"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1011577","article-title":"The circRNA circVAMP3 restricts influenza A virus replication by interfering with NP and NS1 proteins","volume":"19","author":"Min","year":"2023","journal-title":"PloS Pathog"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1080\/15476286.2023.2272118","article-title":"Regulatory circular RNAs in viral diseases: applications in diagnosis and therapy","volume":"20","author":"Wang","year":"2023","journal-title":"RNA Biol"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.2147\/CMAR.S272983","article-title":"Circ-ATP5H induces Hepatitis B virus replication and expression by regulating miR-138-5p\/TNFAIP3 axis","volume":"12","author":"Jiang","year":"2020","journal-title":"Cancer Manag Res"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1011894","article-title":"circMORC3-encoded novel protein negatively regulates antiviral immunity through synergizing with host gene MORC3","volume":"19","author":"Wang","year":"2023","journal-title":"PloS Pathog"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1016\/j.vetmic.2022.109390","article-title":"Identification and characterization of circular RNAs in the A549 cells following Influenza A virus infection","volume":"267","author":"Guo","year":"2022","journal-title":"Vet Microbiol"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.01017-21","article-title":"A novel intronic circular RNA antagonizes influenza virus by absorbing a microRNA that degrades CREBBP and accelerating IFN-\u03b2 production","volume":"12","author":"Qu","year":"2021","journal-title":"mBio"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1261\/rna.2302706","article-title":"RNA-associated protein 55 (RAP55) localizes to mRNA processing bodies and stress granules","volume":"12","author":"Yang","year":"2006","journal-title":"RNA"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1203405109","article-title":"LSm14A is a processing body-associated sensor of viral nucleic acids that initiates cellular antiviral response in the early phase of viral infection","volume":"109","author":"Li","year":"2012","journal-title":"Proc Natl Acad Sci USA"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00647-12","article-title":"The NS1 protein of influenza A virus interacts with cellular processing bodies and stress granules through RNA-associated protein 55 (RAP55) during virus infection","volume":"86","author":"Mok","year":"2012","journal-title":"J Virol"},{"key":"B25","first-page":"97","article-title":"A Highly Efficient Strategy for Overexpressing circRNAs","volume-title":"Methods Mol Biol","author":"Liu","year":"2018"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1006\/meth.2001.1262","article-title":"Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method","volume":"25","author":"Livak","year":"2001","journal-title":"Methods (San Diego Calif)"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1080\/22221751.2025.2502007","article-title":"CircMYO9A inhibits influenza A virus replication by dampening haemagglutinin cleavage via increasing SERPINE1\/PAI-1 expression","volume":"14","author":"Zheng","year":"2025","journal-title":"Emerg Microbes Infect"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1038\/s41423-019-0265-6","article-title":"The zinc-finger protein ZFYVE1 modulates TLR3-mediated signaling by facilitating TLR3 ligand binding","volume":"17","author":"Zhong","year":"2020","journal-title":"Cell Mol Immunol"},{"key":"B29","doi-asserted-by":"publisher","first-page":"22","DOI":"10.1016\/j.molcel.2017.02.017","article-title":"Circ-ZNF609 is a circular RNA that can be translated and functions in myogenesis","volume":"66","author":"Legnini","year":"2017","journal-title":"Mol Cell"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1002\/wrna.1685","article-title":"Circular RNA translation, a path to hidden proteome","volume":"13","author":"Sinha","year":"2022","journal-title":"Wiley Interdiscip Rev RNA"},{"key":"B31","first-page":"67","article-title":"Circular RNAs act as miRNA sponges","volume-title":"Circular Rnas: Biogenesis and Functions","author":"Panda","year":"2018"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2017.05.023","article-title":"Coordinated circRNA biogenesis and function with NF90\/NF110 in viral infection","volume":"67","author":"Li","year":"2017","journal-title":"Mol Cell"},{"key":"B33","doi-asserted-by":"publisher","first-page":"3500","DOI":"10.1016\/j.ymthe.2022.09.021","article-title":"A protein encoded by circular ZNF609 RNA induces acute kidney injury by activating the AKT\/mTOR-autophagy pathway","volume":"30","author":"Ouyang","year":"2022","journal-title":"Mol Ther"},{"key":"B34","doi-asserted-by":"publisher","first-page":"4795","DOI":"10.1038\/s41467-022-32311-2","article-title":"Circular EZH2-encoded EZH2-92aa mediates immune evasion in glioblastoma via inhibition of surface NKG2D ligands","volume":"13","author":"Zhong","year":"2022","journal-title":"Nat Commun"},{"key":"B35","doi-asserted-by":"publisher","first-page":"52","DOI":"10.1124\/jpet.122.001085","article-title":"The functions and mechanisms of translatable circular RNAs","volume":"384","author":"Liu","year":"2023","journal-title":"J Pharmacol Exp Ther"},{"key":"B36","doi-asserted-by":"publisher","first-page":"91","DOI":"10.1007\/s00018-024-05148-9","article-title":"CircYthdc2 generates polypeptides through two translation strategies to facilitate virus escape","volume":"81","author":"Zheng","year":"2024","journal-title":"Cell Mol Life Sci"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1038\/nature11993","article-title":"Natural RNA circles function as efficient microRNA sponges","volume":"495","author":"Hansen","year":"2013","journal-title":"Nature"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2022.975223","article-title":"Circular RNA circ_0076631 promotes coxsackievirus B3 infection through modulating viral translation by sponging miR-214-3p","volume":"13","author":"Qin","year":"2022","journal-title":"Front Microbiol"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.01232-23","article-title":"Hsa_circ_0007321 regulates Zika virus replication through miR-492\/NFKBID\/NF-kappaB signaling pathway","volume":"97","author":"Kang","year":"2023","journal-title":"J Virol"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1186\/s13567-024-01291-0","article-title":"circRNA_8521 promotes Senecavirus A infection by sponging miRNA-324 to regulate LC3A","volume":"55","author":"Yang","year":"2024","journal-title":"Vet Res"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21041511","article-title":"The central role of non-structural protein 1 (NS1) in influenza biology and infection","volume":"21","author":"Rosario-Ferreira","year":"2020","journal-title":"Int J Mol Sci"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1010505","article-title":"Influenza A virus NS1 protein hijacks YAP\/TAZ to suppress TLR3-mediated innate immune response","volume":"18","author":"Zhang","year":"2022","journal-title":"PloS Pathog"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1841925\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T05:36:20Z","timestamp":1783575380000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1841925\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,9]]},"references-count":42,"alternative-id":["10.3389\/fimmu.2026.1841925"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2026.1841925","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,9]]},"article-number":"1841925"}}