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Of note, herpes simplex virus 1 (HSV-1) has been reported to be associated with AD. We sought to identify the transcriptomic changes due to HSV-1 infection and anti-viral drug (acyclovir, ACV) treatment of HSV-1 infection in dissociated cells from human cerebral organoids (dcOrgs) versus stem cell-derived pancreatic islets (sc-islets) to gain potential biological insights into the relevance of HSV-1-induced inflammation in AD and T1D. We observed that differentially expressed genes (DEGs) in HSV-1-infected sc-islets were enriched for genes associated with several autoimmune diseases, most significantly, T1D, but also rheumatoid arthritis, psoriasis, Crohn\u2019s disease, and multiple sclerosis, whereas DEGs in HSV-1-infected dcOrgs were exclusively enriched for genes associated with AD. The ACV treatment of sc-islets was not as effective in rescuing transcript perturbations of autoimmune disease-associated genes. Finally, we identified gene ontology categories that were enriched for DEGs that were in common across, or unique to, viral treatment of dcOrgs and sc-islets, such as categories involved in the transferase complex, mitochondrial, and autophagy function. In addition, we compared transcriptomic signatures from HSV-1-infected sc-islets with sc-islets that were infected with the coxsackie B virus (CVB) that had been associated with T1D pathogenesis. Collectively, this study provides tissue-specific insights into the molecular effects of inflammation in AD and T1D.<\/jats:p>","DOI":"10.3390\/cells13231978","type":"journal-article","created":{"date-parts":[[2024,11,29]],"date-time":"2024-11-29T08:24:14Z","timestamp":1732868654000},"page":"1978","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Herpes Simplex Virus 1 Infection of Human Brain Organoids and Pancreatic Stem Cell-Islets Drives Organoid-Specific Transcripts Associated with Alzheimer\u2019s Disease and Autoimmune Diseases"],"prefix":"10.3390","volume":"13","author":[{"given":"Jonathan","family":"Sundstrom","sequence":"first","affiliation":[{"name":"Department of Medicine, Division of Innate Immunity, University of Massachusetts Chan Medical School, Worcester, MA 01605, USA"},{"name":"Department of Molecular, Cell and Cancer Biology, University of Massachusetts Chan Medical School, Worcester, MA 01605, USA"},{"name":"Department of Neurology, University of Massachusetts Chan Medical School, Worcester, MA 01605, USA"},{"name":"NeuroNexus Institute, University of Massachusetts Chan Medical School, Worcester, MA 01605, USA"},{"name":"Department of Genomics and Computational Biology, University of Massachusetts Chan Medical School, Worcester, MA 01605, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emma","family":"Vanderleeden","sequence":"additional","affiliation":[{"name":"Department of Medicine, Diabetes Center of Excellence, University of Massachusetts Chan Medical School, Worcester, MA 01605, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0383-7741","authenticated-orcid":false,"given":"Nathaniel J.","family":"Barton","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Innate Immunity, University of Massachusetts Chan Medical School, Worcester, MA 01605, 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University of Massachusetts Chan Medical School, Worcester, MA 01605, USA"},{"name":"NeuroNexus Institute, University of Massachusetts Chan Medical School, Worcester, MA 01605, USA"},{"name":"Department of Genomics and Computational Biology, University of Massachusetts Chan Medical School, Worcester, MA 01605, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,11,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1016\/S0140-6736(96)10149-5","article-title":"Herpes simplex virus type 1 in brain and risk of Alzheimer\u2019s disease","volume":"349","author":"Itzhaki","year":"1997","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"eaay8828","DOI":"10.1126\/sciadv.aay8828","article-title":"A 3D human brain-like tissue model of herpes-induced Alzheimer\u2019s disease","volume":"6","author":"Cairns","year":"2020","journal-title":"Sci. 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