{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,26]],"date-time":"2026-10-26T19:34:21Z","timestamp":1793043261802,"version":"4.5.0"},"reference-count":56,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"868","content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Sci. Signal."],"published-print":{"date-parts":[[2025,1,7]]},"abstract":"<jats:p>\n            Infection with herpes simplex virus type 1 (HSV-1) in the brains of\n            <jats:italic>APOE4<\/jats:italic>\n            carriers increases the risk of Alzheimer\u2019s disease (AD). We previously found that latent HSV-1 in a three-dimensional in vitro model of\n            <jats:italic>APOE4<\/jats:italic>\n            -heterozygous human brain tissue was reactivated in response to neuroinflammation caused by exposure to other pathogens. Because traumatic brain injury also causes neuroinflammation, we surmised that brain injury might similarly reactivate latent HSV-1. Here, we examined the effects of one or more controlled blows to our human brain model in the absence or presence of latent HSV-1 infection. After repeated, mild controlled blows, latently infected tissues showed reactivation of HSV-1; the production and accumulation of \u03b2 amyloid and phosphorylated tau (which promotes synaptic dysfunction and neurodegeneration); and activated gliosis, which is associated with destructive neuroinflammation. These effects are collectively associated with AD, dementia, and chronic traumatic encephalopathy (CTE) and were increased with additional injury but were absent in mock-infected tissue. Blocking the cytokine IL-1\u03b2 prevented the induction of amyloid and gliosis in latently infected monolayer cultures after scratch wounding. We thus propose that after repeated mechanical injuries to the brain, such as from direct blows to the head or jarring motions of the head, the resulting reactivation of HSV-1 in the brain may contribute to the development of AD and related diseases in some individuals.\n          <\/jats:p>","DOI":"10.1126\/scisignal.ado6430","type":"journal-article","created":{"date-parts":[[2025,1,7]],"date-time":"2025-01-07T18:58:42Z","timestamp":1736276322000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":43,"title":["Repetitive injury induces phenotypes associated with Alzheimer\u2019s disease by reactivating HSV-1 in a human brain tissue model"],"prefix":"10.1126","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0574-8395","authenticated-orcid":true,"given":"Dana M.","family":"Cairns","sequence":"first","affiliation":[{"name":"Department of Biomedical Engineering, Tufts University, Medford, MA 02155, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9000-3931","authenticated-orcid":true,"given":"Brooke M.","family":"Smiley","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, Tufts University, Medford, MA 02155, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-9537-0465","authenticated-orcid":true,"given":"Jordan A.","family":"Smiley","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, Tufts University, Medford, MA 02155, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasaman","family":"Khorsandian","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, Tufts University, Medford, MA 02155, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marilyn","family":"Kelly","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, Tufts University, Medford, MA 02155, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5167-5276","authenticated-orcid":true,"given":"Ruth F.","family":"Itzhaki","sequence":"additional","affiliation":[{"name":"Institute of Population Ageing, University of Oxford, Oxford OX2 6PR, UK."},{"name":"Division of Neuroscience, School of Biological Sciences, University of Manchester, Manchester M13 9PL, UK."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9245-7774","authenticated-orcid":true,"given":"David L.","family":"Kaplan","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, Tufts University, Medford, MA 02155, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(08)70164-9"},{"key":"e_1_3_2_3_2","unstructured":"K. Carlson S. Kehle L. Meis N. Greer R. MacDonald I. Rutks T. J. Wilt \u201cVA evidence-based synthesis program reports \u201d in The Assessment and Treatment of Individuals with History of Traumatic Brain Injury and Post-Traumatic Stress Disorder: A Systematic Review of the Evidence (US Department of Veterans Affairs 2009)."},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1007\/s13311-020-00840-7"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.3171\/2017.11.JNS171500"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1002\/alz.12315"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awac179"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.3389\/fncel.2019.00528"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1750-3639.2011.00513.x"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1111\/bpa.12532"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1002\/jmv.1890330403"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(96)10149-5"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-220287"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.3390\/vaccines9060679"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.2174\/1570159X15666170313122937"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00406-021-01286-4"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-191337"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.STR.0000086754.32238.DA"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(21)00144-4"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11845-021-02714-z"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1007\/s13555-021-00549-1"},{"key":"e_1_3_2_22_2","first-page":"e18022","article-title":"COVID-19 and herpes simplex virus infection: A cross-sectional study","volume":"13","author":"Shanshal M.","year":"2021","unstructured":"M. Shanshal, H. S. Ahmed, COVID-19 and herpes simplex virus infection: A cross-sectional study. 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Lim Development of a high-throughput quantitative platform using human cerebral organoids to study virus-induced neuroinflammation in Alzheimer\u2019s disease. bioRxiv 2024.03.21.585957 [Preprint] (2024). https:\/\/doi.org\/10.1101\/2024.03.21.585957.","DOI":"10.1101\/2024.03.21.585957"},{"key":"e_1_3_2_56_2","doi-asserted-by":"crossref","unstructured":"J. Sundstrom E. Vanderleeden N. J. Barton S. D. Redick P. Dawes L. F. Murray M. N. Olson K. Tran S. M. Chigas A. R. Orszulak G. M. Church B. Readhead H. S. Oh D. M. Harlan D. M. Knipe J. P. Wang Y. Chan E. T. Lim Herpes simplex virus 1 infection of human brain organoids and pancreatic stem cell-islets drives transcripts associated with Alzheimer\u2019s disease and autoimmune diseases. 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