Preprint Article Version 1 This version is not peer-reviewed

Herpes Simplex Virus 1 Infection of Human Brain Organoids and Pancreatic Stem Cell-Islets Drives Transcripts Associated with Alzheimer’s Disease and Autoimmune Diseases

Version 1 : Received: 15 July 2024 / Approved: 16 July 2024 / Online: 16 July 2024 (08:27:19 CEST)

How to cite: Sundstrom, J.; Vanderleeden, E.; Barton, N. J.; Redick, S. D.; Dawes, P.; Murray, L. F.; Olson, M. N.; Tran, K.; Chigas, S. M.; Orszulak, A. R.; Church, G. M.; Readhead, B.; Oh, H.; Harlan, D. M.; Knipe, D. M.; Wang, J. P.; Chan, Y.; Lim, E. T. Herpes Simplex Virus 1 Infection of Human Brain Organoids and Pancreatic Stem Cell-Islets Drives Transcripts Associated with Alzheimer’s Disease and Autoimmune Diseases. Preprints 2024, 2024071267. https://doi.org/10.20944/preprints202407.1267.v1 Sundstrom, J.; Vanderleeden, E.; Barton, N. J.; Redick, S. D.; Dawes, P.; Murray, L. F.; Olson, M. N.; Tran, K.; Chigas, S. M.; Orszulak, A. R.; Church, G. M.; Readhead, B.; Oh, H.; Harlan, D. M.; Knipe, D. M.; Wang, J. P.; Chan, Y.; Lim, E. T. Herpes Simplex Virus 1 Infection of Human Brain Organoids and Pancreatic Stem Cell-Islets Drives Transcripts Associated with Alzheimer’s Disease and Autoimmune Diseases. Preprints 2024, 2024071267. https://doi.org/10.20944/preprints202407.1267.v1

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 dissoci-ated 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. ACV treatment of sc-islets did not rescue transcript expression 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. Collectively, this studies pro-vide insight to the molecular effects of inflammation in AD and T1D.

Keywords

stem cell islets; cerebral organoids; Type 1 diabetes; Alzheimer’s disease; innate immune; neurodegenerative diseases; autoimmune diseases; acyclovir; herpes simplex virus 1

Subject

Biology and Life Sciences, Immunology and Microbiology

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