{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T21:50:26Z","timestamp":1790718626689,"version":"4.1.0"},"reference-count":53,"publisher":"American Society for Microbiology","issue":"10","license":[{"start":{"date-parts":[[2023,10,31]],"date-time":"2023-10-31T00:00:00Z","timestamp":1698710400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/doi.org\/10.1128\/ASMCopyrightv2"},{"start":{"date-parts":[[2023,10,31]],"date-time":"2023-10-31T00:00:00Z","timestamp":1698710400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"name":"HHS | National Institutes of Health","award":["R01 NS087539"],"award-info":[{"award-number":["R01 NS087539"]}]},{"name":"HHS | National Institutes of Health","award":["R01 NS038932"],"award-info":[{"award-number":["R01 NS038932"]}]},{"name":"HHS | National Institutes of Health","award":["T32 AI007417"],"award-info":[{"award-number":["T32 AI007417"]}]},{"name":"HHS | National Institutes of Health","award":["T32 OD011089"],"award-info":[{"award-number":["T32 OD011089"]}]},{"name":"HHS | National Institutes of Health","award":["K01 OD026529"],"award-info":[{"award-number":["K01 OD026529"]}]},{"name":"HHS | National Institutes of Health","award":["F31 NS101775"],"award-info":[{"award-number":["F31 NS101775"]}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["J Virol"],"published-print":{"date-parts":[[2023,10,31]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Central nervous system (CNS) infection with Sindbis virus (SINV), the prototypic alphavirus, results in encephalomyelitis in a well-established mouse model that is used to characterize immune factors important in controlling viral infection in neurons. We have previously shown that interferon regulatory factor (IRF) 7 is required for survival from SINV encephalomyelitis, as mice deficient in IRF7 (\n            <jats:italic>Irf7<\/jats:italic>\n            <jats:sup>\u2212\/\u2212<\/jats:sup>\n            ) develop paralysis and fatal disease within 7\u20138 days after infection without clearing infectious virus from the CNS. To determine the contributions of this innate immune factor in the prevention of fatal disease, we characterized the antiviral immune response to SINV infection in\n            <jats:italic>Irf7<\/jats:italic>\n            <jats:sup>\u2212\/\u2212<\/jats:sup>\n            and C57BL\/6J [wild-type (WT)] mice.\n            <jats:italic>\n              Irf7\n              <jats:sup>\u2212\/<\/jats:sup>\n            <\/jats:italic>\n            <jats:sup>\u2212<\/jats:sup>\n            mice had prolonged and widespread viral infection in motor neuron-rich regions of the CNS associated with more rapid and severe immunopathology in these regions. Proportions of CD8\n            <jats:sup>+<\/jats:sup>\n            T cells and inflammatory macrophages were higher in\n            <jats:italic>Irf7<\/jats:italic>\n            <jats:sup>\u2212\/\u2212<\/jats:sup>\n            mice following infection, but T cells infiltrating the CNS produced fewer antiviral cytokines than in WT mice. Levels of IFN-\u03b3 and SINV-specific antibody in motor neuron-rich regions of the brain were comparable or higher than WT, indicating that IRF7 deficiency does not impair expression of these immune factors important in facilitating viral clearance. Therefore, IRF7 is required for the clearance of SINV from motor neuron-rich regions of the CNS through a mechanism that either is necessary for the neuronal response to currently identified mediators of infectious virus clearance or enables the production of additional antiviral factor(s) needed for clearance.\n          <\/jats:p>\n          <jats:sec>\n            <jats:title>IMPORTANCE<\/jats:title>\n            <jats:p>\n              Viral encephalomyelitis outcome is dependent on host responses to neuronal infection. Interferon (IFN) is an important component of the innate response, and IFN regulatory factor (IRF) 7 is an inducible transcription factor for the synthesis of IFN-\u03b1. IRF7-deficient mice develop fatal paralysis after CNS infection with Sindbis virus, while wild-type mice recover.\n              <jats:italic>Irf7<\/jats:italic>\n              <jats:sup>\u2212\/\u2212<\/jats:sup>\n              mice produce low levels of IFN-\u03b1 but high levels of IFN-\u03b2 with induction of IFN-stimulated genes, so the reason for this difference is not understood. The current study shows that\n              <jats:italic>Irf7<\/jats:italic>\n              <jats:sup>\u2212\/\u2212<\/jats:sup>\n              mice developed inflammation earlier but failed to clear virus from motor neuron-rich regions of the brainstem and spinal cord. Levels of IFN-\u03b3 and virus-specific antibody were comparable, indicating that IRF7 deficiency does not impair expression of these known viral clearance factors. Therefore, IRF7 is either necessary for the neuronal response to currently identified mediators of clearance or enables the production of additional antiviral factor(s) needed for clearance.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1128\/jvi.00959-23","type":"journal-article","created":{"date-parts":[[2023,9,29]],"date-time":"2023-09-29T13:02:29Z","timestamp":1695992549000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":7,"title":["Interferon regulatory factor 7 modulates virus clearance and immune responses to alphavirus encephalomyelitis"],"prefix":"10.1128","volume":"97","author":[{"given":"Elizabeth M.","family":"Troisi","sequence":"first","affiliation":[{"name":"W. Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health , Baltimore, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8603-4046","authenticated-orcid":false,"given":"Benjamin H.","family":"Nguyen","sequence":"additional","affiliation":[{"name":"W. Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health , Baltimore, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0916-360X","authenticated-orcid":false,"given":"Victoria K.","family":"Baxter","sequence":"additional","affiliation":[{"name":"W. Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health , Baltimore, Maryland, USA"},{"name":"Department of Molecular and Comparative Pathobiology, Johns Hopkins School of Medicine , Baltimore, Maryland, USA"},{"name":"Department of Pathology and Laboratory Medicine, University of North Carolina at Chapel Hill , Chapel Hill, North Carolina, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6643-2429","authenticated-orcid":false,"given":"Diane E.","family":"Griffin","sequence":"additional","affiliation":[{"name":"W. 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