ArticleAnnals of neurology2022
Human Endogenous Retrovirus K Envelope in Spinal Fluid of Amyotrophic Lateral Sclerosis Is Toxic.
Article in Annals of neurology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 48 citations in OpenAlex.
- The therapeutic potential of transposable element activity modulation.EMBO molecular medicine · 2026Review
- Plasma exosomal HERV-K transcripts are increased in amyotrophic lateral sclerosis.BMC neuroscience · 2026Article
- Transcriptional landscapes of dengue patients reveal associations between HERV activity and disease severity.NAR molecular medicine · 2026Article
- Crystal structure of HERV-K envelope glycoprotein surface subunit.Journal of virology · 2026Article
- TDP-43: [GU]-ardian of the transcriptome.Molecular neurodegeneration · 2026Review
- Downregulation of miRNAs Accompanies Increased HERV-K (HML-2) Expression in Amyotrophic Lateral Sclerosis.Molecular neurobiology · 2026Article
- NeuroViOme: a viral orfeome collection for studies of neurodegenerative disease.Journal of neurovirology · 2026Review
- Cutting-edge treatments in amyotrophic lateral sclerosis: the role of molecular pathogenesis in targeted therapies.Stem cell research & therapy · 2025Review
- Strict retroelement regulation is frequently lost following cancer transformation and generates a promising reservoir of cancer biomarkers.Mobile DNA · 2025Article
- Machine learning predicts distinct biotypes of amyotrophic lateral sclerosis.European journal of human genetics : EJHG · 2025Article
- Transposable elements in health and disease: Molecular basis and clinical implications.Chinese medical journal · 2025Review
- Human endogenous retrovirus K (HERV-K) envelope structures in pre- and postfusion by cryo-EM.Science advances · 2025Article
- The prefusion structure of the HERV-K (HML-2) Env spike complex.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Human Endogenous Retroviruses as Novel Therapeutic Targets in Neurodegenerative Disorders.Vaccines · 2025Review
- Retrotransposon: an insight into neurological disorders from perspectives of neurodevelopment and aging.Translational neurodegeneration · 2025Review
- Brain virome dysbiosis in Parkinson's disease and multiple system atrophy.Frontiers in microbiology · 2025Article
- Endogenous retroviruses are dysregulated in ALS.iScience · 2024Article
- Review
- TDP-43 proteinopathy in ALS is triggered by loss of ASRGL1 and associated with HML-2 expression.Nature communications · 2024Article
- Endogenous Retroviruses Unveiled: A Comprehensive Review of Inflammatory Signaling/Senescence-Related Pathways and Therapeutic Strategies.Aging and disease · 2024Review
Corrections and comments
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Authors and funding
20 authors at 3 institutions in 3 countries.
Funding
Abstract
objectiveHuman endogenous retroviruses have been implicated in neurodegenerative diseases including amyotrophic lateral sclerosis (ALS). Expression of human endogenous retrovirus K (HERV-K) subtype HML-2 envelope (Env) in human neuronal cultures and in transgenic mice results in neurotoxicity and neurodegeneration, and mice expressing HML-2 Env display behavioral and neuromuscular characteristics resembling ALS. This study aims to characterize the neurotoxic properties of HML-2 Env.
methodsEnv neurotoxicity was detected in ALS cerebrospinal fluid and confirmed using recombinant Env protein in a cell-based assay and a mouse model. The mechanism of neurotoxicity was assessed with immunoprecipitation followed by mass spectrometry and Western blot, and by screening a panel of inhibitors.
resultsWe observed that recombinant HML-2 Env protein caused neurotoxicity resulting in neuronal cell death, retraction of neurites, and decreased neuronal electrical activity. Injection of the Env protein into the brains of mice also resulted in neuronal cell death. HML-2 Env protein was also found in the cerebrospinal fluid of patients with sporadic ALS. The neurotoxic properties of the Env and the cerebrospinal fluid could be rescued with the anti-Env antibody. The Env was found to bind to CD98HC complexed to β1 integrin on the neuronal cell surface. Using a panel of compounds to screen for their ability to block Env-induced neurotoxicity, we found that several compounds were protective and are linked to the β1 integrin pathway.
interpretationHERV-K Env is released extracellularly in ALS and causes neurotoxicity via a novel mechanism. Present results pave the way for new treatment strategies in sporadic ALS. ANN NEUROL 2022;92:545-561.
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