{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T06:47:51Z","timestamp":1789541271310,"version":"build-2803163510"},"reference-count":74,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2022,9,17]],"date-time":"2022-09-17T00:00:00Z","timestamp":1663372800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100006108","name":"NIH","doi-asserted-by":"publisher","award":["R03TR002937"],"award-info":[{"award-number":["R03TR002937"]}],"id":[{"id":"10.13039\/100006108","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006108","name":"NIH","doi-asserted-by":"publisher","award":["P20GM103546"],"award-info":[{"award-number":["P20GM103546"]}],"id":[{"id":"10.13039\/100006108","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006108","name":"NIH","doi-asserted-by":"publisher","award":["R41TR003929"],"award-info":[{"award-number":["R41TR003929"]}],"id":[{"id":"10.13039\/100006108","id-type":"DOI","asserted-by":"publisher"}]},{"name":"UM Center for Translational Medicine","award":["R03TR002937"],"award-info":[{"award-number":["R03TR002937"]}]},{"name":"UM Center for Translational Medicine","award":["P20GM103546"],"award-info":[{"award-number":["P20GM103546"]}]},{"name":"UM Center for Translational Medicine","award":["R41TR003929"],"award-info":[{"award-number":["R41TR003929"]}]},{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","award":["R03TR002937"],"award-info":[{"award-number":["R03TR002937"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","award":["P20GM103546"],"award-info":[{"award-number":["P20GM103546"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","award":["R41TR003929"],"award-info":[{"award-number":["R41TR003929"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Rift Valley fever virus (RVFV) is a pathogenic human and livestock RNA virus that poses a significant threat to public health and biosecurity. During RVFV infection, the atypical kinase RIOK3 plays important roles in the innate immune response. Although its exact functions in innate immunity are not completely understood, RIOK3 has been shown to be necessary for mounting an antiviral interferon (IFN) response to RVFV in epithelial cells. Furthermore, after immune stimulation, the splicing pattern for RIOK3 mRNA changes markedly, and RIOK3\u2032s dominant alternatively spliced isoform, RIOK3 X2, exhibits an opposite effect on the IFN response by dampening it. Here, we further investigate the roles of RIOK3 and its spliced isoform in other innate immune responses to RVFV, namely the NF\u03baB-mediated inflammatory response. We find that while RIOK3 is important for negatively regulating this inflammatory pathway, its alternatively spliced isoform, RIOK3 X2, stimulates it. Overall, these data demonstrate that both RIOK3 and its X2 isoform have unique roles in separate innate immune pathways that respond to RVFV infection.<\/jats:p>","DOI":"10.3390\/v14092064","type":"journal-article","created":{"date-parts":[[2022,9,21]],"date-time":"2022-09-21T00:08:09Z","timestamp":1663718889000},"page":"2064","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["RIOK3 and Its Alternatively Spliced Isoform Have Disparate Roles in the Innate Immune Response to Rift Valley Fever Virus (MP12) Infection"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0238-1156","authenticated-orcid":false,"given":"Thomas C.","family":"Bisom","sequence":"first","affiliation":[{"name":"Department of Chemistry and Biochemistry, University of Montana, Missoula, MT 59801, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luke A.","family":"White","sequence":"additional","affiliation":[{"name":"Division of Biological Sciences, University of Montana, Missoula, MT 59801, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean-Marc","family":"Lanchy","sequence":"additional","affiliation":[{"name":"Division of Biological Sciences, University of Montana, Missoula, MT 59801, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8087-5362","authenticated-orcid":false,"given":"J. Stephen","family":"Lodmell","sequence":"additional","affiliation":[{"name":"Division of Biological Sciences, University of Montana, Missoula, MT 59801, USA"},{"name":"Center for Biomolecular Structure and Dynamics, University of Montana, Missoula, MT 59801, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,9,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1586","DOI":"10.3389\/fimmu.2019.01586","article-title":"Comparative Structure and Function Analysis of the RIG-I-Like Receptors: RIG-I and MDA5","volume":"10","author":"Brisse","year":"2019","journal-title":"Front. Immunol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"730","DOI":"10.1038\/ni1087","article-title":"The RNA helicase RIG-I has an essential function in double-stranded RNA-induced innate antiviral responses","volume":"5","author":"Yoneyama","year":"2004","journal-title":"Nat. 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