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 (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 - PNAS, 120(38), e2308187120. National Academy of Sciences 10.1073/pnas.2308187120
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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 neutralizing anti-ENV therapeutic antibody. Yet direct proof of its mode of action can only be presented here based on transgenic ENV expression in mice. Upon demyelination, we observed myelin repair deficits, neurotoxic microglia and astroglia, and increased axon degeneration. Experimental autoimmune encephalomyelitis activity progressed faster in mutant mice equally accompanied by activated glial cells. This study therefore provides direct evidence on HERV-W ENV's contribution to the overall negative impact of this activated viral entity in MS.
Item Type: |
Journal Article (Original Article) |
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Division/Institute: |
04 Faculty of Medicine > Department of Head Organs and Neurology (DKNS) > Clinic of Neurology |
UniBE Contributor: |
Küry, Patrick |
Subjects: |
600 Technology > 610 Medicine & health |
ISSN: |
1091-6490 |
Publisher: |
National Academy of Sciences |
Language: |
English |
Submitter: |
Pubmed Import |
Date Deposited: |
21 Sep 2023 08:17 |
Last Modified: |
21 Dec 2023 15:00 |
Publisher DOI: |
10.1073/pnas.2308187120 |
PubMed ID: |
37695891 |
Uncontrolled Keywords: |
endogenous retrovirus glia multiple sclerosis myelin repair neurodegeneration |
BORIS DOI: |
10.48350/186234 |
URI: |
https://boris.unibe.ch/id/eprint/186234 |
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