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Deckers, Thomas

University of British Columbia

Multiple sclerosis (MS) is a chronic neurodegenerative disease that results in the destruction of the myelin sheath by autoreactive immune cells that infiltrate into the central nervous system (CNS) through the blood brain barrier. The mechanisms underlying the onset and progression of MS remain poorly understood, and treatment options for late-stage progressive MS are limited. Therefore, there is a need for deeper understanding of the factors affecting MS pathology. Endogenous retroviruses (ERVs) are found in MS patient blood and brains and are linked to inflammation and other autoimmune diseases. However, the cause and effect of ERV expression in MS remain largely unknown. We analyzed three public bulk RNA-seq datasets of MS patient samples to study changes in ERV expression across different regions of the brain. We found that ERVs correlate with several genes that support necroptosis in the corpus callosum. Through a phylogenetic analysis, we identified GATA2 transcription factor as a putative regulator of ERV expression in MS. Furthermore, using an unbiased approach, we found that ERVs that correlate with GATA2 also correlate with a set of immune genes and heat shock proteins from the Hsp70 family across multiple independent MS cohorts. Using snRNA-seq, we found that these ERVs are mainly expressed in neurons, while others are expressed in microglia and ependymal cells. Lastly, we identified a set of ERVs that are expressed by peripheral B cells in MS patients, some of which also correlated with abundance of cytomegalovirus transcript. Together, we uncovered ERVs that have previously not been associated with MS and found novel associations between ERV expression and different aspects of MS biology.

Text

2025-04-23

Attribution-NonCommercial 4.0 International

http://hdl.handle.net/2429/90717

Bioinformatics

University of British Columbia

UBCV

http://creativecommons.org/licenses/by-nc/4.0/