{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T22:18:49Z","timestamp":1789769929377,"version":"4.0.1"},"reference-count":27,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T00:00:00Z","timestamp":1782259200000},"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:p>N-Myc and STAT interactor (NMI), initially identified as a Myc- and STAT-associated protein, is increasingly recognized as a regulatory node in innate antiviral immunity. Current evidence indicates that NMI does not exert a fixed antiviral or proviral effect. Instead, its functional output is shaped by interacting partners, signaling pathway context, subcellular localization, and stage of infection. In selected acute RNA virus models, NMI suppresses IRF7-dependent type I interferon (IFN-I) signaling. In the IAV model, this involves an NMI\u2013IFP35 complex coupled to the TRIM21\u2013IRF7 axis that promotes IRF7 degradation, suppresses IFN-I responses, and thereby facilitates viral replication. In foamy virus infection, by contrast, NMI directly binds the viral transactivator Tas, retains it in the cytoplasm, and suppresses viral transcription, thus acting as a host restriction factor. In human cytomegalovirus (HCMV) infection, NMI appears to function as a host pathway component targeted by viral antagonism, as the viral protein UL23 interferes with the NMI\u2013STAT1\/IFN-\u03b3 axis and dampens antiviral gene expression. In addition, extracellular NMI and IFP35 can function as damage-associated molecular patterns that amplify inflammation. Together, these findings support the view that NMI acts as a context-dependent molecular switch rather than a unidirectional effector in innate antiviral immunity.<\/jats:p>","DOI":"10.3389\/fimmu.2026.1864248","type":"journal-article","created":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T05:56:03Z","timestamp":1782280563000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["N-Myc and STAT interactor as a context-dependent switch in innate antiviral immunity"],"prefix":"10.3389","volume":"17","author":[{"given":"Lin","family":"Han","sequence":"first","affiliation":[{"name":"Department of Preventive Veterinary Medicine, College of Veterinary Medicine, Northeast Agricultural University","place":["Harbin, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinyao","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Preventive Veterinary Medicine, College of Veterinary Medicine, Northeast Agricultural University","place":["Harbin, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fangfang","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Preventive Veterinary Medicine, College of Veterinary Medicine, Northeast Agricultural University","place":["Harbin, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luyu","family":"Mao","sequence":"additional","affiliation":[{"name":"Department of Preventive Veterinary Medicine, College of Veterinary Medicine, Northeast Agricultural University","place":["Harbin, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongli","family":"Guo","sequence":"additional","affiliation":[{"name":"Department of Immunology, School of Basic Medical Sciences, Harbin Medical University","place":["Harbin, Heilongjiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingchun","family":"Gao","sequence":"additional","affiliation":[{"name":"Department of Preventive Veterinary Medicine, College of Veterinary Medicine, Northeast Agricultural University","place":["Harbin, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,6,24]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1038\/ni1303","article-title":"Innate immune recognition of viral infection","volume":"7","author":"Kawai","year":"2006","journal-title":"Nat Immunol"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1038\/s12276-021-00691-y","article-title":"Regulation of antiviral innate immune signaling and viral evasion following viral genome sensing","volume":"53","author":"Chathuranga","year":"2021","journal-title":"Exp Mol Med"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-immunol-032713-120231","article-title":"Interferon-stimulated genes: a complex web of host defenses","volume":"32","author":"Schneider","year":"2014","journal-title":"Annu Rev Immunol"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1189\/jlb.0603252","article-title":"Interferon-gamma: an overview of signals, mechanisms and functions","volume":"75","author":"Schroder","year":"2004","journal-title":"J Leukoc Biol"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1038\/s41577-018-0029-z","article-title":"IFN\u03b3: signalling, epigenetics and roles in immunity, metabolism, disease and cancer immunotherapy","volume":"18","author":"Ivashkiv","year":"2018","journal-title":"Nat Rev Immunol"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)80965-4","article-title":"Functional association of Nmi with Stat5 and Stat1 in IL-2- and IFNgamma-mediated signaling","volume":"96","author":"Zhu","year":"1999","journal-title":"Cell"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M006975200","article-title":"Interferon-inducible Myc\/STAT-interacting protein Nmi associates with IFP35 into a high molecular mass complex and inhibits proteasome-mediated degradation of IFP35","volume":"275","author":"Chen","year":"2000","journal-title":"J Biol Chem"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1300740","article-title":"Negative regulation of Nmi on virus-triggered type I IFN production by targeting IRF7","volume":"191","author":"Wang","year":"2013","journal-title":"J Immunol"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1016\/j.virol.2015.08.013","article-title":"Trim21 regulates Nmi-IFI35 complex-mediated inhibition of innate antiviral response","volume":"485","author":"Das","year":"2015","journal-title":"Virology"},{"key":"B10","doi-asserted-by":"publisher","first-page":"30","DOI":"10.1165\/rcmb.2020-0391OC","article-title":"NMI facilitates influenza A virus infection by promoting degradation of IRF7 through TRIM21","volume":"65","author":"Ouyang","year":"2021","journal-title":"Am J Respir Cell Mol Biol"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1016\/j.psj.2024.104269","article-title":"N-Myc and STAT interactor degrades interferon regulatory factor 7 mediated type I interferon signaling to promote duck Tembusu virus replication","volume":"103","author":"Luo","year":"2024","journal-title":"Poult Sci"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00799-14","article-title":"N-Myc interactor inhibits prototype foamy virus by sequestering viral Tas protein in the cytoplasm","volume":"88","author":"Hu","year":"2014","journal-title":"J Virol"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.02249-07","article-title":"IFP35 is involved in the antiviral function of interferon by association with the viral Tas transactivator of bovine foamy virus","volume":"82","author":"Tan","year":"2008","journal-title":"J Virol"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1006867","article-title":"Human cytomegalovirus UL23 inhibits transcription of IFN-gamma-stimulated genes and blocks antiviral IFN-gamma responses by interacting with human N-Myc interactor protein","volume":"14","author":"Feng","year":"2018","journal-title":"PloS Pathog"},{"key":"B15","doi-asserted-by":"publisher","first-page":"950","DOI":"10.1038\/s41467-017-00930-9","article-title":"NMI and IFP35 serve as proinflammatory DAMPs during cellular infection and injury","volume":"8","author":"Xiahou","year":"2017","journal-title":"Nat Commun"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.2300012","article-title":"Interaction of Nmi and IFP35 promotes mutual protein stabilization and IRF3 and IRF7 degradation to suppress type I IFN production in teleost fish","volume":"210","author":"Li","year":"2023","journal-title":"J Immunol"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1096\/fj.202301450RR","article-title":"N-MYC-interacting protein enhances type II interferon signaling by inhibiting STAT1 sumoylation","volume":"37","author":"Feng","year":"2023","journal-title":"FASEB J"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.02049","article-title":"TRIM21-from intracellular immunity to therapy","volume":"10","author":"Foss","year":"2019","journal-title":"Front Immunol"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.3390\/ijms24021683","article-title":"Multiple roles of TRIM21 in virus infection","volume":"24","author":"Li","year":"2023","journal-title":"Int J Mol Sci"},{"key":"B20","doi-asserted-by":"publisher","first-page":"493","DOI":"10.1146\/annurev-pathmechdis-012419-032847","article-title":"DAMPs, PAMPs, and LAMPs in immunity and sterile inflammation","volume":"15","author":"Zindel","year":"2020","journal-title":"Annu Rev Pathol"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.3390\/v3050561","article-title":"Foamy virus biology and its application for vector development","volume":"3","author":"Lindemann","year":"2011","journal-title":"Viruses"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1016\/j.virusres.2010.10.031","article-title":"Human cytomegalovirus immunity and immune evasion","volume":"157","author":"Jackson","year":"2011","journal-title":"Virus Res"},{"key":"B23","doi-asserted-by":"publisher","first-page":"87","DOI":"10.1038\/nri3787","article-title":"Type I interferons in infectious disease","volume":"15","author":"McNab","year":"2015","journal-title":"Nat Rev Immunol"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1016\/j.coviro.2011.10.008","article-title":"Interferon-stimulated genes and their antiviral effector functions","volume":"1","author":"Schoggins","year":"2011","journal-title":"Curr Opin Virol"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2021.110126","article-title":"IFP35 as a promising biomarker and therapeutic target for the syndromes induced by SARS-CoV-2 or influenza virus","volume":"37","author":"Yu","year":"2021","journal-title":"Cell Rep"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.3390\/v16050811","article-title":"Advancements in research on duck Tembusu virus infections","volume":"16","author":"Cheng","year":"2024","journal-title":"Viruses"},{"key":"B27","doi-asserted-by":"publisher","first-page":"4206","DOI":"10.1038\/s41467-026-72732-x","article-title":"The ISG Atlas: a loss-of-function analysis characterizes antiviral properties of interferon stimulated genes","volume":"17","author":"Krey","year":"2026","journal-title":"Nat Commun"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1864248\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T05:56:07Z","timestamp":1782280567000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1864248\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,24]]},"references-count":27,"alternative-id":["10.3389\/fimmu.2026.1864248"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2026.1864248","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,24]]},"article-number":"1864248"}}