Gruchot, JoelJoelGruchotReiche, LauraLauraReicheWerner, LuisaLuisaWernerHerrero, FelisaFelisaHerreroSchira-Heinen, JessicaJessicaSchira-HeinenMeyer, UrsUrsMeyerKüry, PatrickPatrickKüry2024-10-262024-10-262024-06-27https://boris-portal.unibe.ch/handle/20.500.12422/178587The endogenous retrovirus type W (HERV-W) is a human-specific entity, which was initially discovered in multiple sclerosis (MS) patient derived cells. We initially found that the HERV-W envelope (ENV) protein negatively affects oligodendrogenesis and controls microglial cell polarization towards a myelinated axon associated and damaging phenotype. Such first functional assessments were conducted ex vivo, given the human-specific origin of HERV-W. Recent experimental evidence gathered on a novel transgenic mouse model, mimicking activation and expression of the HERV-W ENV protein, revealed that all glial cell types are impacted and that cellular fates, differentiation, and functions were changed. In order to identify HERV-W-specific signatures in glial cells, the current study analyzed the transcriptome of ENV protein stimulated microglial- and astroglial cells and compared the transcriptomic signatures to lipopolysaccharide (LPS) stimulated cells, owing to the fact that both ligands can activate toll-like receptor-4 (TLR-4). Additionally, a comparison between published disease associated glial signatures and the transcriptome of HERV-W ENV stimulated glial cells was conducted. We, therefore, provide here for the first time a detailed molecular description of specific HERV-W ENV evoked effects on those glial cell populations that are involved in smoldering neuroinflammatory processes relevant for progression of neurodegenerative diseases.enHuman endogenous retrovirus type W glia multiple sclerosis neurodegeneration neuroinflammation600 - Technology::610 - Medicine & healtharticle10.48350/1983163894410910.1016/j.micinf.2024.105382