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We examined whether IL-1 signaling contributes to the encephalitis observed in mouse adenovirus type 1 (MAV-1) infection, using mice lacking the IL-1 receptor (<jats:italic>Il1r1<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup>mice).<jats:italic>Il1r1<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup>mice demonstrated reduced survival, greater disruption of the blood-brain barrier (BBB), higher brain viral loads, and higher brain inflammatory cytokine and chemokine levels than control C57BL\/6J mice. We also examined infections of mice defective in IL-1\u03b2 production (<jats:italic>Pycard<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup>mice) and mice defective in trafficking of Toll-like receptors to the endosome (<jats:italic>Unc93b1<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup>mice).<jats:italic>Pycard<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup>and<jats:italic>Unc93b1<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup>mice showed lower survival (similar to<jats:italic>Il1r1<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup>mice) than control mice but, unlike<jats:italic>Il1r1<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup>mice, did not have increased brain viral loads or BBB disruption. Based on the brain cytokine levels, MAV-1-infected<jats:italic>Unc93b1<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup>mice had a very different inflammatory profile from infected<jats:italic>Il1r1<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup>and<jats:italic>Pycard<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup>mice. Histological examination demonstrated pathological findings consistent with encephalitis in control and knockout mice; however, intranuclear viral inclusions were seen only in<jats:italic>Il1r1<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup>mice. A time course of infection of control and<jats:italic>Il1r1<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup>mice evaluating the kinetics of viral replication and cytokine production revealed differences between the mouse strains primarily at 7 to 8 days after infection, when mice began succumbing to MAV-1 infection. In the absence of IL-1 signaling, we noted an increase in the transcription of type I interferon (IFN)-stimulated genes. Together, these results indicate that IL-1 signaling is important during MAV-1 infection and suggest that, in its absence, increased IFN-\u03b2 signaling may result in increased neuroinflammation.<\/jats:p><jats:p><jats:bold>IMPORTANCE<\/jats:bold>The investigation of encephalitis pathogenesis produced by different viruses is needed to characterize virus and host-specific factors that contribute to disease. MAV-1 produces viral encephalitis in its natural host, providing a good model for studying factors involved in encephalitis development. We investigated the role of IL-1 signaling during MAV-1-induced encephalitis. Unexpectedly, the lack of IL-1 signaling increased the mortality and inflammation in mice infected with MAV-1. Also, there was an increase in the transcription of type I IFN-stimulated genes that correlated with the observed increased mortality and inflammation. The findings highlight the complex nature of encephalitis and suggests that IL-1 has a protective effect for the development of MAV-1-induced encephalitis.<\/jats:p>","DOI":"10.1128\/jvi.02106-16","type":"journal-article","created":{"date-parts":[[2016,12,1]],"date-time":"2016-12-01T03:30:38Z","timestamp":1480563038000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":15,"title":["A Protective Role for Interleukin-1 Signaling during Mouse Adenovirus Type 1-Induced Encephalitis"],"prefix":"10.1128","volume":"91","author":[{"given":"Luiza A.","family":"Castro-Jorge","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology, University of Michigan, Ann Arbor, Michigan, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carla D.","family":"Pretto","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of Michigan, Ann Arbor, 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