{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T04:56:45Z","timestamp":1790657805444,"version":"4.1.0"},"posted":{"date-parts":[[2026,7,14]]},"group-title":"Immunology","reference-count":69,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T00:00:00Z","timestamp":1783987200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/publicdomain\/zero\/1.0\/"}],"funder":[{"name":"Division of Intramural Research, National Institute of Allergy and Infectious Diseases, NIH","award":["1ZIAAI001125-16"],"award-info":[{"award-number":["1ZIAAI001125-16"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,7,14]]},"abstract":"<jats:title>Summary<\/jats:title>\n                <jats:p>\n                  Type-I interferons (IFN-I) and IFN-stimulated genes (ISGs) are central to antiviral defense, while dysregulation can drive autoimmunity.\n                  <jats:italic>IFNB1<\/jats:italic>\n                  expression is controlled by a highly ordered multiprotein complex composed of IRF3\/7, NF\u03baB, and ATF2\/c-Jun (AP-1) that recruit coactivators and chromatin-remodeling proteins to expose the\n                  <jats:italic>IFNB1<\/jats:italic>\n                  promoter for the RNA polymerase II (RNA Pol II) transcriptional machinery. Here, we identified the paraspeckle protein non-POU domain-containing octamer-binding protein (NONO) as a critical facilitator of innate immune activation. Loss of NONO enhanced replication of multiple orthoflaviviruses including West Nile virus due to impaired induction of IFN-I and ISGs. NONO did not affect upstream signaling but instead promoted chromatin accessibility and promoter access for RNA Pol II to drive expression of\n                  <jats:italic>IFNB1<\/jats:italic>\n                  , ISGs, and proinflammatory cytokines. These findings position NONO as a key regulator of antiviral gene expression and reveal chromatin-levels of control that determine effective antiviral immunity.\n                <\/jats:p>","DOI":"10.64898\/2026.07.11.737985","type":"posted-content","created":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T00:00:12Z","timestamp":1784073612000},"source":"Crossref","is-referenced-by-count":1,"title":["The paraspeckle protein NONO potentiates the antiviral innate immune response through chromatin regulation"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7668-892X","authenticated-orcid":false,"given":"Adam","family":"Hage","sequence":"first","affiliation":[{"name":"Innate Immunity and Pathogenesis Section, Laboratory of Neurological Infections and Immunity, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT 59840, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mikhaila","family":"Janes","sequence":"additional","affiliation":[{"name":"Innate Immunity and Pathogenesis Section, Laboratory of Neurological Infections and Immunity, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT 59840, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Byron","family":"Shue","sequence":"additional","affiliation":[{"name":"Innate Immunity and Pathogenesis Section, Laboratory of Neurological Infections and Immunity, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT 59840, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tovah E.","family":"Markowitz","sequence":"additional","affiliation":[{"name":"Integrated Data Sciences Section, Research Technologies Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda MD 20892, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suhyeon","family":"Yoon","sequence":"additional","affiliation":[{"name":"Integrated Data Sciences Section, Research Technologies Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda MD 20892, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey G.","family":"Shannon","sequence":"additional","affiliation":[{"name":"Innate Immunity and Pathogenesis Section, Laboratory of Neurological Infections and Immunity, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT 59840, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul A.","family":"Beare","sequence":"additional","affiliation":[{"name":"Research Technologies Branch, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT 59840, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebecca M.","family":"Broeckel","sequence":"additional","affiliation":[{"name":"Innate Immunity and Pathogenesis Section, Laboratory of Virology, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT 59840, USA"},{"name":"Dispatch Biotherapeutics, Philadelphia, PA 19104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Justin B.","family":"Lack","sequence":"additional","affiliation":[{"name":"Integrated Data Sciences Section, Research Technologies Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda MD 20892, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Craig","family":"Martens","sequence":"additional","affiliation":[{"name":"Research Technologies Branch, Rocky Mountain Laboratories, National 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