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The prototypic alphavirus, Sindbis virus (SINV), primarily infects neurons in mice, resulting in neurologic disease involving both the brain and spinal cord. Interferon (IFN) regulatory factor (IRF) 7-deficient mice (\n                    <jats:italic>Irf7<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    ) rapidly succumb to SINV infection with extensive immunopathology while wildtype mice experience only mild disease and recover. IRF7 is widely recognized to be the main transcription factor required for the amplification of type I IFN, specifically IFN\u03b1, as\n                    <jats:italic>Irf7<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice do not produce IFN\u03b1 but do express IFN\u03b2. However, based on the current experimental evidence, it is not clear if the severe outcome of SINV infection in\n                    <jats:italic>Irf7<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice is due to the absence of IFN\u03b1 or heretofore unappreciated noncanonical actions of IRF7. In this study, we demonstrate that the administration of IFN\u03b1 to\n                    <jats:italic>Irf7<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice early in infection restricted SINV replication and largely rescued the animals from severe disease and mortality but did not alter the nature of CNS inflammation. Further, Cre-Lox-mediated deletion of\n                    <jats:italic>Irf7<\/jats:italic>\n                    in myeloid cells (\n                    <jats:italic>Irf7<\/jats:italic>\n                    <jats:sup>fl\/fl<\/jats:sup>\n                    Lyz2-cre mice) resulted in severe disease and lethality despite significantly higher peak levels of IFN\u03b1 than WT animals, suggesting that the lethal phenotype of\n                    <jats:italic>Irf7<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice was attributed to the myeloid cell-specific loss of IRF7 and not to the loss of IFN\u03b1 production. Both\n                    <jats:italic>Irf7<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    and\n                    <jats:italic>Irf7<\/jats:italic>\n                    <jats:sup>fl\/fl<\/jats:sup>\n                    Lyz2-cre mice had increased levels of monocytes infiltrating into the brain compared to WT, indicating a potential role for IRF7 in the trafficking and activation of myeloid cells. Therefore, while IFN\u03b1 supplementation may contribute to reducing disease severity by restricting virus replication, disease was ultimately exacerbated by the increased infiltration of inflammatory myeloid cells in\n                    <jats:italic>Irf7<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice.\n                  <\/jats:p>","DOI":"10.1186\/s12974-026-03936-7","type":"journal-article","created":{"date-parts":[[2026,6,25]],"date-time":"2026-06-25T02:24:51Z","timestamp":1782354291000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["IRF7 deficiency in myeloid cells results in increased disease severity and death during alphavirus encephalomyelitis despite intact expression of type I interferons"],"prefix":"10.1186","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8603-4046","authenticated-orcid":false,"given":"Benjamin H.","family":"Nguyen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elise","family":"Stanley","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wanmin","family":"Dai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth M.","family":"Troisi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diane E.","family":"Griffin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,6,25]]},"reference":[{"issue":"2","key":"3936_CR1","doi-asserted-by":"publisher","first-page":"12","DOI":"10.1007\/s11910-017-0724-3","volume":"17","author":"CT Doughty","year":"2017","unstructured":"Doughty CT, Yawetz S, Lyons J. 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