Transgenic expression of the HERV-W envelope protein leads to polarized glial cell populations and a neurodegenerative environment

Gruchot, Joel; Lewen, Isabel; Dietrich, Michael; Reiche, Laura; Sindi, Mustafa; Hecker, Christina; Herrero, Felisa; Charvet, Benjamin; Weber-Stadlbauer, Ulrike; Hartung, Hans-Peter; Albrecht, Philipp; Perron, Hervé; Meyer, Urs; Küry, Patrick

doi:10.5167/uzh-253485

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Gruchot, J., Lewen, I., Dietrich, M., Reiche, L., Sindi, M., Hecker, C., Herrero, F., Charvet, B., Weber-Stadlbauer, U., Hartung, H.-P., Albrecht, P., Perron, H., Meyer, U., & Küry, P. (2023). Transgenic expression of the HERV-W envelope protein leads to polarized glial cell populations and a neurodegenerative environment. Proceedings of the National Academy of Sciences of the United States of America, 120, e2308187120. https://doi.org/10.1073/pnas.2308187120

Abstract

The human endogenous retrovirus type W (HERV-W) has been identified and repeatedly confirmed as human-specific pathogenic entity affecting many cell types in multiple sclerosis (MS). Our recent contributions revealed the encoded envelope (ENV) protein to disturb myelin repair by interfering with oligodendroglial precursor differentiation and by polarizing microglial cells toward an axon-damage phenotype. Indirect proof of ENV’s antiregenerative and degenerative activities has been gathered recently in clinical trials using a neutraliz