{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,27]],"date-time":"2026-01-27T16:06:30Z","timestamp":1769529990189,"version":"3.49.0"},"reference-count":102,"publisher":"Oxford University Press (OUP)","issue":"10","license":[{"start":{"date-parts":[[2020,5,1]],"date-time":"2020-05-01T00:00:00Z","timestamp":1588291200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["1DP1DA043915"],"award-info":[{"award-number":["1DP1DA043915"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010280","name":"John H. 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Remarkably, RdRP mice never develop autoinflammation, interferonopathy, or other discernible abnormalities. In this study, we used RNA sequencing and other methods to analyze ISG expression across five time points from fetal development to adulthood in wild-type and RdRP mice. In RdRP mice, the proportion of upregulated ISGs increased during development, with the most dramatic induction occurring 2 wk postnatally. The amplified ISG profile is then maintained lifelong. Molecular pathways and biological functions associated with innate immune and IFN signaling are only activated postnatally, suggesting constrained fetal responsiveness to innate immune stimuli. Biological functions supporting replication of viruses are only inhibited postnatally. We further determined that the RdRP is expressed at low levels and that blocking Ifnar1 reverses the amplified ISG transcriptome in adults. In conclusion, the upregulated ISG profile of RdRP mice is mostly triggered early postnatally, is maintained through adulthood, and requires ongoing type I IFN signaling to maintain it. The model provides opportunities to study the systems biology of innate immunity and to determine how sustained ISG upregulation can be compatible with robust health.<\/jats:p>","DOI":"10.4049\/jimmunol.1901421","type":"journal-article","created":{"date-parts":[[2020,4,10]],"date-time":"2020-04-10T19:35:12Z","timestamp":1586547312000},"page":"2791-2807","source":"Crossref","is-referenced-by-count":3,"title":["Development of IFN-Stimulated Gene Expression from Embryogenesis through Adulthood, with and without Constitutive MDA5 Pathway Activation"],"prefix":"10.1093","volume":"204","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6433-9263","authenticated-orcid":false,"given":"Laura","family":"Bankers","sequence":"first","affiliation":[{"name":"Division of Infectious Diseases, Anschutz Medical Campus, University of Colorado Denver School of Medicine , Aurora, CO 80045"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0552-5415","authenticated-orcid":false,"given":"Caitlin","family":"Miller","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Anschutz Medical Campus, University of Colorado Denver School of Medicine , Aurora, CO 80045"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guoqi","family":"Liu","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Anschutz Medical Campus, University of Colorado Denver School of Medicine , Aurora, CO 80045"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5614-5570","authenticated-orcid":false,"given":"Chommanart","family":"Thongkittidilok","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Anschutz Medical Campus, University of Colorado Denver School of Medicine , Aurora, CO 80045"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"James","family":"Morrison","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Anschutz Medical Campus, University of Colorado Denver School of Medicine , Aurora, CO 80045"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1598-5415","authenticated-orcid":false,"given":"Eric M","family":"Poeschla","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Anschutz Medical Campus, University of Colorado Denver School of Medicine , Aurora, CO 80045"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2020,5,15]]},"reference":[{"key":"2025030417511886700_r1","doi-asserted-by":"crossref","first-page":"360","DOI":"10.1038\/nrmicro.2016.45","article-title":"Viral evasion of intracellular DNA and RNA sensing","volume":"14","author":"Chan","year":"2016","journal-title":"Nat. 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Biotechnol."},{"key":"2025030417511886700_r49","doi-asserted-by":"crossref","first-page":"562","DOI":"10.1038\/nprot.2012.016","article-title":"Differential gene and transcript expression analysis of RNA-seq experiments with TopHat and Cufflinks. [Published erratum appears in 2014 Nat. Protoc. 9: 2513.]","volume":"7","author":"Trapnell","year":"2012","journal-title":"Nat. Protoc."},{"key":"2025030417511886700_r50","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1186\/s13059-016-0881-8","article-title":"A survey of best practices for RNA-seq data analysis. [Published erratum appears in 2016 Genome Biol. 17: 181.]","volume":"17","author":"Conesa","year":"2016","journal-title":"Genome Biol."},{"key":"2025030417511886700_r51","author":"Goff","year":"2013"},{"key":"2025030417511886700_r52","author":"Plotly Technologies Inc","year":"2015"},{"key":"2025030417511886700_r53","doi-asserted-by":"crossref","first-page":"D1040","DOI":"10.1093\/nar\/gks1215","article-title":"Interferome v2.0: an updated database of annotated interferon-regulated genes","volume":"41","author":"Rusinova","year":"2013","journal-title":"Nucleic Acids Res."},{"key":"2025030417511886700_r54","author":"QIAGEN Inc"},{"key":"2025030417511886700_r55","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1038\/75556","article-title":"Gene ontology: tool for the unification of biology. The Gene Ontology Consortium","volume":"25","author":"Ashburner","year":"2000","journal-title":"Nat. Genet."},{"key":"2025030417511886700_r56","doi-asserted-by":"crossref","first-page":"D330","DOI":"10.1093\/nar\/gky1055","article-title":"The gene ontology resource: 20 years and still GOing strong","volume":"47","author":"The Gene Ontology Consortium","year":"2019","journal-title":"Nucleic Acids Res."},{"key":"2025030417511886700_r57","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1093\/nar\/gkn923","article-title":"Bioinformatics enrichment tools: paths toward the comprehensive functional analysis of large gene lists","volume":"37","author":"Huang","year":"2009","journal-title":"Nucleic Acids Res."},{"key":"2025030417511886700_r58","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1038\/nprot.2008.211","article-title":"Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources","volume":"4","author":"Huang","year":"2009","journal-title":"Nat. Protoc."},{"key":"2025030417511886700_r59","doi-asserted-by":"crossref","first-page":"458","DOI":"10.1038\/nm.3108","article-title":"Differential innate immune response programs in neuronal subtypes determine susceptibility to infection in the brain by positive-stranded RNA viruses","volume":"19","author":"Cho","year":"2013","journal-title":"Nat. Med."},{"key":"2025030417511886700_r60","doi-asserted-by":"crossref","first-page":"912","DOI":"10.1189\/jlb.69.6.912","article-title":"Functional classification of interferon-stimulated genes identified using microarrays","volume":"69","author":"de Veer","year":"2001","journal-title":"J. Leukoc. Biol."},{"key":"2025030417511886700_r61","doi-asserted-by":"crossref","first-page":"690","DOI":"10.1111\/j.1365-2893.2006.00732.x","article-title":"Expressional screening of interferon-stimulated genes for antiviral activity against hepatitis C virus replication","volume":"13","author":"Itsui","year":"2006","journal-title":"J. Viral Hepat."},{"key":"2025030417511886700_r62","doi-asserted-by":"crossref","first-page":"8332","DOI":"10.1128\/JVI.02199-09","article-title":"Identification of five interferon-induced cellular proteins that inhibit west nile virus and dengue virus infections","volume":"84","author":"Jiang","year":"2010","journal-title":"J. Virol."},{"key":"2025030417511886700_r63","doi-asserted-by":"crossref","first-page":"513","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. 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Immunol."},{"key":"2025030417511886700_r67","doi-asserted-by":"crossref","first-page":"2295","DOI":"10.1101\/gad.11.18.2295","article-title":"Rho GTPases and signaling networks","volume":"11","author":"Van Aelst","year":"1997","journal-title":"Genes Dev."},{"key":"2025030417511886700_r68","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1016\/j.tcb.2005.01.002","article-title":"Regulation of innate immunity by Rho GTPases","volume":"15","author":"Bokoch","year":"2005","journal-title":"Trends Cell Biol."},{"key":"2025030417511886700_r69","doi-asserted-by":"crossref","DOI":"10.3390\/cells8070733","article-title":"RhoA as a key regulator of innate and adaptive immunity","author":"Bros","year":"2019","journal-title":"Cells."},{"key":"2025030417511886700_r70","doi-asserted-by":"crossref","first-page":"pe1","DOI":"10.1126\/stke.3162006pe1","article-title":"The significance of interferon-gamma-triggered internalization of tight-junction proteins in inflammatory bowel disease","volume":"2006","author":"Chiba","year":"2006","journal-title":"Sci. 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Biochem."},{"key":"2025030417511886700_r77","doi-asserted-by":"crossref","first-page":"684","DOI":"10.1016\/j.it.2015.09.009","article-title":"Impact of early-life exposures on immune maturation and susceptibility to disease","volume":"36","author":"Gollwitzer","year":"2015","journal-title":"Trends Immunol."},{"key":"2025030417511886700_r78","doi-asserted-by":"crossref","first-page":"1562","DOI":"10.1126\/science.1164511","article-title":"Maternal alloantigens promote the development of tolerogenic fetal regulatory T cells in utero","volume":"322","author":"Mold","year":"2008","journal-title":"Science"},{"key":"2025030417511886700_r79","doi-asserted-by":"crossref","first-page":"271","DOI":"10.4049\/jimmunol.1700859","article-title":"Embryonic lethality and host immunity of RelA-deficient mice are mediated by both apoptosis and necroptosis","volume":"200","author":"Xu","year":"2018","journal-title":"J. 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Dis."},{"key":"2025030417511886700_r89","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1016\/S0378-1119(99)00516-8","article-title":"Ermap, a gene coding for a novel erythroid specific adhesion\/receptor membrane protein","volume":"242","author":"Ye","year":"2000","journal-title":"Gene"},{"key":"2025030417511886700_r90","doi-asserted-by":"crossref","first-page":"652","DOI":"10.1038\/ni807","article-title":"Hlx is induced by and genetically interacts with T-bet to promote heritable T(H)1 gene induction","volume":"3","author":"Mullen","year":"2002","journal-title":"Nat. Immunol."},{"key":"2025030417511886700_r91","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1083\/jcb.145.2.413","article-title":"The integrin alpha9beta1 mediates adhesion to activated endothelial cells and transendothelial neutrophil migration through interaction with vascular cell adhesion molecule-1","volume":"145","author":"Taooka","year":"1999","journal-title":"J. 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