{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T15:10:15Z","timestamp":1785424215878,"version":"3.56.0"},"posted":{"date-parts":[[2026,3,17]]},"group-title":"Immunology","reference-count":85,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,3,17]],"date-time":"2026-03-17T00:00:00Z","timestamp":1773705600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.biorxiv.org\/about\/FAQ#license"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["R00 AG53412"],"award-info":[{"award-number":["R00 AG53412"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"id":[{"id":"https:\/\/ror.org\/03f1p6998","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,3,17]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Viral pathogens cause neurologic sequelae during acute and post-acute phases of infection. CD8\n                  <jats:sup>+<\/jats:sup>\n                  T cells are hypothesized to contribute to these effects, but the mechanisms through which they act are poorly understood. We posited that viral infections and\/or antiviral immune responses induce DNA damage, which may underlie neuronal dysfunction. Using a model of neurotropic flavivirus infection, we found that genes associated with interstrand crosslinking (ICL) DNA damage were upregulated post-infection, temporally congruent with T cell infiltration. Using an\n                  <jats:italic>in vitro<\/jats:italic>\n                  co-culture system, our results demonstrate that CD8\n                  <jats:sup>+<\/jats:sup>\n                  T cells induced ICL-like damage in primary neurons, independent of antigen-specific interactions or direct contact. Human transcriptomic data also showed overexpression of genes associated with ICL damage in the brains of people with Parkinson\u2019s disease, Alzheimer\u2019s disease, and multiple sclerosis, which are neurologic diseases characterized by neuroinflammation. Together, these data indicate that CD8\n                  <jats:sup>+<\/jats:sup>\n                  T cells cause genotoxic DNA damage in neurons, which may underlie the neurologic dysfunction seen in neurodegenerative conditions.\n                <\/jats:p>\n                <jats:sec>\n                  <jats:title>Summary<\/jats:title>\n                  <jats:p>\n                    Results indicate that CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells induce interstrand crosslinking-like DNA damage in neurons independent of antigen-specificity in a mouse model of viral infection,\n                    <jats:italic>in vitro<\/jats:italic>\n                    primary cell culture system, and human neurologic diseases. These findings provide insight on the mechanistic connection between neuroinflammation and neurologic dysfunction.\n                  <\/jats:p>\n                <\/jats:sec>","DOI":"10.64898\/2026.03.14.711737","type":"posted-content","created":{"date-parts":[[2026,3,17]],"date-time":"2026-03-17T22:15:14Z","timestamp":1773785714000},"source":"Crossref","is-referenced-by-count":0,"title":["CD8\u207a T cells induce interstrand crosslinking-associated DNA damage in neurons"],"prefix":"10.64898","author":[{"given":"Britanie M.","family":"Blackhurst","sequence":"first","affiliation":[{"name":"Department of Biological Sciences, University of North Carolina at Charlotte, Charlotte, North Carolina, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aayush","family":"Bhatt","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, University of North Carolina at Charlotte, Charlotte, North Carolina, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emily","family":"Kretchmer","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, University of North Carolina at Charlotte, Charlotte, North Carolina, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Autumn E.","family":"Tucker","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, University of North Carolina at Charlotte, Charlotte, North Carolina, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bree","family":"Kurtz","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, University of North Carolina at Charlotte, Charlotte, North Carolina, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katie L.","family":"Reagin","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, University of North Carolina at Charlotte, Charlotte, North Carolina, 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