{"doi":"10.3390/cells13231978","title":"Herpes Simplex Virus 1 Infection of Human Brain Organoids and Pancreatic Stem Cell-Islets Drives Organoid-Specific Transcripts Associated with Alzheimer’s Disease and Autoimmune Diseases","abstract":"Viral infections leading to inflammation have been implicated in several common diseases, such as Alzheimer's disease (AD) and type 1 diabetes (T1D). 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's 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.","journal":"Cells","year":2024,"id":429556,"datarank":0.3616293827457611,"base_score":2.1972245773362196,"endowment":2.1972245773362196,"self_citation_contribution":0.32958368660043297,"citation_network_contribution":0.032045696145328144,"self_endowment_contribution":0.32958368660043297,"citer_contribution":0.032045696145328144,"corpus_percentile":null,"corpus_rank":null,"citation_count":8,"citer_count":7,"citers_with_citation_signal":1,"citers_with_endowment":1,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9574,"is_data_producer":true,"deposit_databanks":{"GEO":["GSE272361"]},"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":999712,"name":"Emma Vanderleeden","orcid":null,"position":1,"is_corresponding":false},{"id":775832,"name":"Nathaniel Barton","orcid":"0000-0002-0383-7741","position":2,"is_corresponding":false},{"id":439665,"name":"Sambra D. 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Church","orcid":"0000-0003-3535-2076","position":10,"is_corresponding":false},{"id":16904,"name":"Ben Readhead","orcid":"0000-0003-4353-9965","position":11,"is_corresponding":false},{"id":1150123,"name":"Hyung Suk Oh","orcid":"0000-0002-1739-0389","position":12,"is_corresponding":false},{"id":295051,"name":"David M. Harlan","orcid":"0000-0002-6938-8109","position":13,"is_corresponding":false},{"id":392218,"name":"David M. Knipe","orcid":"0000-0003-1554-6236","position":14,"is_corresponding":false},{"id":104332,"name":"Jennifer Wang","orcid":"0000-0002-2556-9100","position":15,"is_corresponding":false},{"id":587109,"name":"Yingleong Chan","orcid":"0000-0003-4474-6114","position":16,"is_corresponding":false},{"id":60376,"name":"Elaine T. 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