{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T10:15:04Z","timestamp":1785406504371,"version":"3.56.0"},"posted":{"date-parts":[[2026,2,25]]},"group-title":"Neuroscience","reference-count":62,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,2,25]],"date-time":"2026-02-25T00:00:00Z","timestamp":1771977600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"award":["105190"],"award-info":[{"award-number":["105190"]}],"id":[{"id":"https:\/\/ror.org\/0375f4d26","id-type":"ROR","asserted-by":"publisher"}]},{"award":["R35NS116835"],"award-info":[{"award-number":["R35NS116835"]}],"id":[{"id":"https:\/\/ror.org\/01s5ya894","id-type":"ROR","asserted-by":"publisher"}]},{"award":["T32 NS121727"],"award-info":[{"award-number":["T32 NS121727"]}],"id":[{"id":"https:\/\/ror.org\/01s5ya894","id-type":"ROR","asserted-by":"publisher"}]},{"award":["F31NS141599"],"award-info":[{"award-number":["F31NS141599"]}],"id":[{"id":"https:\/\/ror.org\/01s5ya894","id-type":"ROR","asserted-by":"publisher"}]},{"award":["R01AG081599"],"award-info":[{"award-number":["R01AG081599"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]},{"award":["U54 AG054349"],"award-info":[{"award-number":["U54 AG054349"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,2,25]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Recent studies revealed key immunological mechanisms within the central nervous system (CNS) that contribute to Alzheimer\u2019s disease pathology. Additionally, analyses of human AD datasets have also associated viral encephalitis exposure (i.e., viral-induced neuroinflammation) with the development of AD and dementia, highlighting the need to better understand how viral encephalitis and neuroimmune mechanisms within the brain may impact AD pathologies such as A\u03b2 plaque deposition. Intracranial infection of susceptible mice with the neurotropic JHM strain of murine coronavirus (JHMV) results in acute encephalomyelitis characterized by viral infection of glia and a robust inflammatory response comprised of monocytes\/macrophages and T cells that aid in controlling viral replication.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>To determine how coronavirus-induced encephalitis may impact established A\u03b2 plaque deposition, we intracranially inoculated JHMV into aged 5xFAD model of amyloidosis. We utilize immunohistochemical and biochemical analysis to assess the impact on existing A\u03b2 pathology. We also utilize spatial transcriptomic imaging to explore how viral encephalitis affects cellular responses to plaque pathology with single-cell resolution.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>\n                    In aged 5xFAD mice, JHMV-induced encephalitis at 12 days p.i. resulted in minimal changes to overall A\u03b2 protein within the brain. However, viral encephalitis induces CD4\n                    <jats:sup>+<\/jats:sup>\n                    and CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cell infiltration and more\n                    <jats:italic>Lgals3\/<\/jats:italic>\n                    MAC2-expressing macrophages surrounding dense-core A\u03b2 plaques, which appear more compacted in JHMV-infected 5xFAD brains compared to uninfected 5xFAD controls. We compared gene expression within JHMV-infected 5xFAD mice and uninfected controls to identify distinct cellular responses to A\u03b2 plaques that differed. Utilizing differential gene expression and pathway analysis, we found that viral encephalitis increased the proportion of myeloid cells in the 5xFAD brain, which also showed down-regulated disease-associated (DAM) pathways involving A\u03b2 clearance, response to lipids, and macrophage activation within the post-encephalitis 5xFAD brains.\n                  <\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Together, these findings suggest an attenuated myeloid cell response to A\u03b2 plaque burden in 5xFAD mice following acute viral encephalitis. Future experiments aim to further dissect inflammatory mechanisms between infiltrating myeloid cells, T cells, and the progression of A\u03b2 and tau pathology. Data derived from these experiments will further elucidate the viral-induced neuroimmune mechanisms that affect AD pathology and offer an opportunity to determine how these neuropathologic changes, such as subsequent neuronal damage, occur.<\/jats:p>\n                <\/jats:sec>","DOI":"10.64898\/2026.02.23.707587","type":"posted-content","created":{"date-parts":[[2026,2,25]],"date-time":"2026-02-25T17:30:15Z","timestamp":1772040615000},"source":"Crossref","is-referenced-by-count":0,"title":["Characterization of effects of a neurotropic murine coronavirus infection on Alzheimer\u2019s disease neuropathology of 5xFAD mice"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4243-8372","authenticated-orcid":false,"given":"Dominic I.","family":"Javonillo","sequence":"first","affiliation":[{"name":"Department of Neurobiology & Behavior, University of California, Irvine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susana","family":"Furman","sequence":"additional","affiliation":[{"name":"Department of Neurobiology & Behavior, University of California, Irvine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucas","family":"Le","sequence":"additional","affiliation":[{"name":"Department of Neurobiology & Behavior, University of California, Irvine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kellie","family":"Fernandez","sequence":"additional","affiliation":[{"name":"Department of Neurobiology & Behavior, University of California, Irvine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jazmyn","family":"Mulford","sequence":"additional","affiliation":[{"name":"Department of Neurobiology & Behavior, University of California, Irvine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vidushi","family":"Singla","sequence":"additional","affiliation":[{"name":"Department of Neurobiology & Behavior, University of California, Irvine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roshni","family":"Jha","sequence":"additional","affiliation":[{"name":"Department of Neurobiology & Behavior, University of California, Irvine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kate Inman","family":"Tsourmas","sequence":"additional","affiliation":[{"name":"Department of Neurobiology & Behavior, University of California, Irvine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nellie E.","family":"Kwang","sequence":"additional","affiliation":[{"name":"Department of Neurobiology & Behavior, University of California, Irvine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kim N.","family":"Green","sequence":"additional","affiliation":[{"name":"Department of Neurobiology & Behavior, University of California, Irvine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas E.","family":"Lane","sequence":"additional","affiliation":[{"name":"Department of Neurobiology & Behavior, University of California, Irvine"},{"name":"Deparment of Molecular Biology & Biochemistry, University of California, Irvine"},{"name":"Center for Virus Research, University of California, Irvine"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026022718500799000_2026.02.23.707587v1.1","unstructured":"Alzheimer\u2019s Association. 2023 Alzheimer\u2019s Disease Facts and Figures. 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