{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T11:58:13Z","timestamp":1792670293934,"version":"4.5.0"},"reference-count":84,"publisher":"American Society for Microbiology","issue":"9","license":[{"start":{"date-parts":[[2015,5,1]],"date-time":"2015-05-01T00:00:00Z","timestamp":1430438400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["J Virol"],"published-print":{"date-parts":[[2015,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Oropouche virus (OROV) is a member of the\n            <jats:named-content content-type=\"genus-species\">Orthobunyavirus<\/jats:named-content>\n            genus in the\n            <jats:named-content content-type=\"genus-species\">Bunyaviridae<\/jats:named-content>\n            family and a prominent cause of insect-transmitted viral disease in Central and South America. Despite its clinical relevance, little is known about OROV pathogenesis. To define the host defense pathways that control OROV infection and disease, we evaluated OROV pathogenesis and immune responses in primary cells and mice that were deficient in the RIG-I-like receptor signaling pathway (MDA5, RIG-I, or MAVS), downstream regulatory transcription factors (IRF-3 or IRF-7), beta interferon (IFN-\u03b2), or the receptor for type I IFN signaling (IFNAR). OROV replicated to higher levels in primary fibroblasts and dendritic cells lacking MAVS signaling, the transcription factors IRF-3 and IRF-7, or IFNAR than in wild-type (WT) cells. In mice, deletion of IFNAR, MAVS, or IRF-3 and IRF-7 resulted in uncontrolled OROV replication, hypercytokinemia, extensive liver damage, and death, whereas WT congenic animals failed to develop disease. Unexpectedly, mice with a selective deletion of IFNAR on myeloid cells (CD11c Cre\n            <jats:sup>+<\/jats:sup>\n            <jats:italic>Ifnar<\/jats:italic>\n            <jats:sup>f\/f<\/jats:sup>\n            or LysM Cre\n            <jats:sup>+<\/jats:sup>\n            <jats:italic>Ifnar<\/jats:italic>\n            <jats:sup>f\/f<\/jats:sup>\n            ) did not sustain enhanced disease with OROV or a selective (flox\/flox) deletion La Crosse virus, a closely related encephalitic orthobunyavirus. In bone marrow chimera studies, recipient irradiated\n            <jats:italic>Ifnar<\/jats:italic>\n            <jats:sup>\u2212\/\u2212<\/jats:sup>\n            mice reconstituted with WT hematopoietic cells sustained high levels of OROV replication and liver damage, whereas WT mice reconstituted with\n            <jats:italic>Ifnar<\/jats:italic>\n            <jats:sup>\u2212\/\u2212<\/jats:sup>\n            bone marrow were resistant to disease. Collectively, these results establish a dominant protective role for MAVS, IRF-3 and IRF-7, and IFNAR in restricting OROV infection and tissue injury and suggest that IFN signaling in nonmyeloid cells contributes to the host defense against orthobunyaviruses.\n          <\/jats:p>\n          <jats:p>\n            <jats:bold>IMPORTANCE<\/jats:bold>\n            Oropouche virus (OROV) is an emerging arthropod-transmitted orthobunyavirus that causes episodic outbreaks of a debilitating febrile illness in humans in countries of South and Central America. The continued expansion of the range and number of its arthropod vectors increases the likelihood that OROV will spread into new regions. At present, the pathogenesis of OROV in humans or other vertebrate animals remains poorly understood. To define cellular mechanisms of control of OROV infection, we performed infection studies in a series of primary cells and mice that were deficient in key innate immune genes involved in pathogen recognition and control. Our results establish that a MAVS-dependent type I IFN signaling pathway has a dominant role in restricting OROV infection and pathogenesis\n            <jats:italic>in vivo<\/jats:italic>\n            .\n          <\/jats:p>","DOI":"10.1128\/jvi.00077-15","type":"journal-article","created":{"date-parts":[[2015,2,26]],"date-time":"2015-02-26T16:52:16Z","timestamp":1424969536000},"page":"4720-4737","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":77,"title":["Oropouche Virus Infection and Pathogenesis Are Restricted by MAVS, IRF-3, IRF-7, and Type I Interferon Signaling Pathways in Nonmyeloid Cells"],"prefix":"10.1128","volume":"89","author":[{"given":"Jose Luiz","family":"Proenca-Modena","sequence":"first","affiliation":[{"name":"Department of Medicine, Washington University School of Medicine, St. Louis, Missouri, USA"},{"name":"Department of Genetics, Evolution and Bioagents, Institute of Biology, University of Campinas (UNICAMP), Campinas, S\u00e3o Paulo, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renata","family":"Sesti-Costa","sequence":"additional","affiliation":[{"name":"Department of Pathology &amp; Immunology, Washington University School of Medicine, St. Louis, Missouri, USA"},{"name":"Department of Biochemistry and Immunology, University of S\u00e3o Paulo (USP) Ribeir\u00e3o Preto School of Medicine, S\u00e3o Paulo, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amelia K.","family":"Pinto","sequence":"additional","affiliation":[{"name":"Department of Medicine, Washington University School of Medicine, St. Louis, Missouri, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Justin M.","family":"Richner","sequence":"additional","affiliation":[{"name":"Department of Medicine, Washington University School of Medicine, St. Louis, Missouri, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helen M.","family":"Lazear","sequence":"additional","affiliation":[{"name":"Department of Medicine, Washington University School of Medicine, St. Louis, Missouri, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tiffany","family":"Lucas","sequence":"additional","affiliation":[{"name":"Department of Medicine, Washington University School of Medicine, St. Louis, Missouri, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer L.","family":"Hyde","sequence":"additional","affiliation":[{"name":"Department of Medicine, Washington University School of Medicine, St. Louis, Missouri, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael S.","family":"Diamond","sequence":"additional","affiliation":[{"name":"Department of Medicine, Washington University School of Medicine, St. Louis, Missouri, USA"},{"name":"Department of Pathology &amp; Immunology, Washington University School of Medicine, St. Louis, Missouri, USA"},{"name":"Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, Missouri, USA"},{"name":"Center for Human Immunology and Immunotherapy Programs, Washington University School of Medicine, St. Louis, Missouri, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","first-page":"695","volume-title":"Virus taxonomy classification and nomenclature of viruses","author":"Fauquet CM","year":"2005","unstructured":"Fauquet CM, Mayo MA, Maniloff J, Desselberger U, Ball LA. 2005. 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