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Human endogenous retrovirus type W envelope protein inhibits oligodendroglial precursor cell differentiation
Abstract
Objective: Differentiation of oligodendroglial precursor cells is crucial for central nervous system remyelination and is influenced by both extrinsic and intrinsic factors. Recent studies showed that human endogenous retrovirus type W (HERV‐W) contributes significantly to brain damage. In particular, its envelope protein ENV can mediate injury to specific cell types of the brain and immune system. Here, we investigated whether ENV protein affects oligodendroglial differentiation. Methods: Immunostaining and gene expression analyses were performed to establish the expression and regulation of the known ENV receptor, Toll‐like receptor 4 (TLR4), on oligodendroglial precursor cells in human brain tissue and in culture. Cultured primary oligodendroglial precursor cells were stimulated with ENV protein to determine the effects of this ligand/receptor interaction. Results: We demonstrated that the ENV protein is present in close proximity to TLR4‐expressing oligodendroglial precursor cells adjacent to multiple sclerosis lesions. Human and rat oligodendroglial precursor cells expressed TLR4, and the ENV‐mediated activation of TLR4 led to the induction of proinflammatory cytokines and inducible nitric oxide synthase as well as the formation of nitrotyrosine groups and a subsequent reduction in myelin protein expression. Interpretation: Our findings suggest that ENV‐mediated induction of nitrosative stress via activation of TLR4 results in an overall reduction of the oligodendroglial differentiation capacity, thereby contributing to remyelination failure. Therefore, pharmacological or antibody‐mediated inhibition of ENV may prevent the blockade of myelin repair in the diseased or injured central nervous system. Ann Neurol 2013;74:721–732
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“Several exogenous and endogenous viruses have been considered in MS pathogenesis, with the most compelling evidence implicating respectively Epstein-Barr virus (EBV)40 and human endogenous retrovirus type-W (HERV-W)41.”
From Locus for severity implicates CNS resilience in progression of multiple sclerosis (2023) · cites this paper as [41]
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Metadata
- Authors
- Kremer, D., Schichel, T., Förster, M., Tzekova, N., Bernard, C., van der Valk, P., van Horssen, J., Hartung, H., Perron, H., & Küry, P.
- Affiliations
- Heinrich Heine University Düsseldorf (DE)
- GeNeuro Geneva Switzerland
- Amsterdam UMC Location Vrije Universiteit Amsterdam (NL)
- Corresponding author
- Küry, Patrick
- ORCID
- Venue
- Annals of Neurology
- Publisher
- Wiley
- Published
- 2013-09-16
- Volume
- 74
- Issue
- 5
- Pages
- 721-732
- ISSN
- 0364-5134 (ISSN-L)
- 1531-8249
- OpenAlex
- W2103327619
- Cited by
- 178
- References
- 50
- Citations by year
- 2026: 5 · 2025: 10 · 2024: 13 · 2023: 12 · 2022: 12 · 2021: 23 · 2020: 8 · 2019: 25 · 2018: 16 · 2017: 15 · 2016: 16 · 2015: 13 · 2014: 8 · 2013: 2
- FWCI
- 9.74
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Annals of Neurology (publishedVersion)
- PubMed (publishedVersion)
- Amsterdam UMC (VU Amsterdam) - Institutional Repository (publishedVersion)
- Pure Amsterdam UMC (submittedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Funders
- Rose Foundation for Communities and the Environment
- Topics
- Health Sciences › Medicine › Clinical Neurology › Multiple Sclerosis Research Studies
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- cell differentiation, remyelination, TLR4, multiple sclerosis, nitrosative stress, inducible nitric oxide synthase, nitrotyrosine, inflammatory cytokines, central nervous system injury
- MeSH terms
- Animals, Cell Differentiation, Cells, Cultured, Humans, Myelin Sheath, Oligodendroglia, Pregnancy Proteins, Gene Products, env, Toll-Like Receptor 4, Rats, Neural Stem Cells
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