ArticleProceedings of the National Academy of Sciences of the United States of America2019
pHERV-W envelope protein fuels microglial cell-dependent damage of myelinated axons in multiple sclerosis.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 71 papers.
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Who cites it
71 citing papers in PubMed, 114 citations in OpenAlex.
- Multiple Sclerosis and Viruses: « Liaisons Dangereuses ».Reviews in medical virology · 2026Review
- The therapeutic potential of transposable element activity modulation.EMBO molecular medicine · 2026Review
- Viral associations in multiple sclerosis: pathogenetic mechanisms and therapeutic implications.Virology journal · 2026Review
- Human Endogenous Retroviruses in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Emerging Roles in Pathogenesis, Immunity, Biomarkers and Therapeutics.International journal of molecular sciences · 2026Review
- Nucleoside-Analog Reverse-Transcriptase Inhibitors (NRTIs) Against Multiple Sclerosis: Comprehensive Review on a Possible Novel Therapeutic Approach.Neurology international · 2026Review
- Alterations of placental HERV expression as a result of gestational COVID-19 disease.Frontiers in microbiology · 2026Article
- The relationship between HERVs and exogenous viral infections: A focus on the value of HERVs in disease prediction and treatment.Virulence · 2025Review
- Human Endogenous Retroviruses and Diseases.MedComm · 2025Review
- Exosomal pHERV-W ENV as a dynamic biomarker for relapse prediction and prognosis in multiple sclerosis.Journal of neuroinflammation · 2025Article
- Recapitulation and reversal of neuropsychiatric phenotypes in a mouse model of human endogenous retrovirus type W expression.Molecular psychiatry · 2025Article
- Human endogenous retrovirus W family envelope protein (ERVWE1) regulates macroautophagy activation and micromitophagy inhibition via NOXA1 in schizophrenia.Virologica Sinica · 2025Article
- Human Endogenous Retroviruses as Novel Therapeutic Targets in Neurodegenerative Disorders.Vaccines · 2025Review
- Multiple sclerosis and infection: history, EBV, and the search for mechanism.Microbiology and molecular biology reviews : MMBR · 2025Review
- An integrated approach for the accurate detection of HERV-K HML-2 transcription and protein synthesis.Nucleic acids research · 2025Article
- Human endogenous retroviruses in schizophrenia: clinical evidence, molecular mechanisms, and implications.Frontiers in cellular and infection microbiology · 2025Review
- Interaction of HERVs with PAMPs in Dysregulation of Immune Response Cascade Upon SARS-CoV-2 Infections.International journal of molecular sciences · 2024Review
- Multiple sclerosis: a narrative overview of current pharmacotherapies and emerging treatment prospects.Pharmacological reports : PR · 2024Review
- Review
- Human endogenous retrovirus W in multiple sclerosis: transcriptional activity is associated with decline in oligodendrocyte proportions in the white matter of the brain.Journal of neurovirology · 2024Article
- HERV-W upregulation expression in bipolar disorder and schizophrenia: unraveling potential links to systemic immune/inflammation status.Retrovirology · 2024Article
11 more citing papers are in PubMed but not listed here.
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14 authors at 3 institutions in 3 countries.
Funding
Abstract
Axonal degeneration is central to clinical disability and disease progression in multiple sclerosis (MS). Myeloid cells such as brain-resident microglia and blood-borne monocytes are thought to be critically involved in this degenerative process. However, the exact underlying mechanisms have still not been clarified. We have previously demonstrated that human endogenous retrovirus type W (HERV-W) negatively affects oligodendroglial precursor cell (OPC) differentiation and remyelination via its envelope protein pathogenic HERV-W (pHERV-W) ENV (formerly MS-associated retrovirus [MSRV]-ENV). In this current study, we investigated whether pHERV-W ENV also plays a role in axonal injury in MS. We found that in MS lesions, pHERV-W ENV is present in myeloid cells associated with axons. Focusing on progressive disease stages, we could then demonstrate that pHERV-W ENV induces a degenerative phenotype in microglial cells, driving them toward a close spatial association with myelinated axons. Moreover, in pHERV-W ENV-stimulated myelinated cocultures, microglia were found to structurally damage myelinated axons. Taken together, our data suggest that pHERV-W ENV-mediated microglial polarization contributes to neurodegeneration in MS. Thus, this analysis provides a neurobiological rationale for a recently completed clinical study in MS patients showing that antibody-mediated neutralization of pHERV-W ENV exerts neuroprotective effects.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.