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Cited by 482Amyotrophic Lateral Sclerosis ResearchAlzheimer's disease research and treatmentsHereditary Neurological Disorders

Human endogenous retrovirus-K contributes to motor neuron disease

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Li, Wenxue, Lee, Myoung-Hwa, Henderson, Lisa, Tyagi, Richa, Bachani, Muzna, Steiner, Joseph, Campanac, Emilie, Hoffman, Dax A. +10 more·2015·Science Translational Medicine
DOI 10.1126/scitranslmed.aac8201PMC PMC6344353
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Abstract

Human endogenous retrovirus-K is activated in the cortical neurons of patients with amyotrophic lateral sclerosis, and expression of the viral envelope protein in mouse brain reproduces the clinical and pathological phenotype of this disease.

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Crossref · 10.1126/scitranslmed.aac8201

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  • A causal association between HERV-K and neuronal dysfunction has previously been established, as ectopic expression of HERV-K or the retroviral envelope protein decreases synaptic activity and induces progressive motor dysfunction in mice.

    “A causal association between HERV-K and neuronal dysfunction has previously been established, as ectopic expression of HERV-K or the retroviral envelope protein that it encodes decreases synaptic activity and induces progressive motor dysfunction in mice8”

    From Pathogenic tau-induced piRNA depletion promotes neuronal death through transposable element dysregulation in neurodegenerative tauopathies (2018) · cites this paper as [8]

    The Results section (“HERV-K env transgenic animals develop motor dysfunction”; page not supplied) reports progressive motor dysfunction and a decrease in spontaneous excitatory postsynaptic current amplitude in mice expressing HERV-K env. It does not show those outcomes in mice expressing the entire HERV-K genome; the Results section reports whole-genome expression only in human neuronal cultures. “Decreases synaptic activity” is also broader than the specific synaptic measure that fell. (LLM, conf=0.84)

    Experimental — accuracy not yet measured

  • The extent to which transposable elements are involved in human disorders and drive disease pathogenesis is currently unknown.

    “While transposable element activation has also been implicated in cancer6, and TDP-43 mediated neurodegeneration7–9, the extent to which transposable elements are involved in human disorders and drive disease pathogenesis is currently unknown.”

    From Pathogenic tau-induced piRNA depletion promotes neuronal death through transposable element dysregulation in neurodegenerative tauopathies (2018) · cites this paper as [8]

  • Elevated HERV-K transcripts are associated with amyotrophic lateral sclerosis and many human cancers.

    “Elevated HERV-K transcripts are associated with amyotrophic lateral sclerosis (ALS)8 and many human cancers, including melanoma, breast cancer, germ cell tumors, renal cancer, and ovarian cancer42”

    From Pathogenic tau-induced piRNA depletion promotes neuronal death through transposable element dysregulation in neurodegenerative tauopathies (2018) · cites this paper as [8]

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Research works printed but not linked: 46

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Authors
Li, W., Lee, M.-H., Henderson, L., Tyagi, R., Bachani, M., Steiner, J., Campanac, E., Hoffman, D. A., von Geldern, G., Johnson, K., Maric, D., Morris, H. D., Lentz, M., Pak, K., Mammen, A., Ostrow, L., Rothstein, J., & Nath, A.
Affiliations
  • National Institutes of Health (US)
  • Section of Infections of the Nervous System, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA.
  • Johns Hopkins University (US)
Corresponding author
  • Li, Wenxue
  • Lee, Myoung-Hwa
  • Nath, Avindra
ORCID
Venue
Science Translational Medicine
Publisher
American Association for the Advancement of Science (AAAS)
Published
2015-09-30
Volume
7
Issue
307
Pages
307ra153-307ra153
ISSN
  • 1946-6234 (ISSN-L)
  • 1946-6242
DOI
10.1126/scitranslmed.aac8201
PMC
PMC6344353
OpenAlex
W2236767140
Cited by
482
References
2
Citations by year
2026: 28 · 2025: 41 · 2024: 43 · 2023: 43 · 2022: 53 · 2021: 65 · 2020: 47 · 2019: 40 · 2018: 49 · 2017: 36 · 2016: 29 · 2015: 8
FWCI
28.67
Type
journal article
Language
en
Open access
Licence
www.sciencemag.org/about/science-licenses-journal-article-reuse (vor, 366 d)
Locations
  • Science Translational Medicine (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Institute of Arthritis, Musculoskeletal and Skin Diseases
  • National Institute of Neurological Disorders and Stroke
  • NICHD of the NIH
Topics
  • Health Sciences › Medicine › Neurology › Amyotrophic Lateral Sclerosis Research
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Hereditary Neurological Disorders
Keywords
HERV-K, amyotrophic lateral sclerosis, motor neuron disease, retroviral envelope protein, neurodegeneration, long terminal repeat, neurite retraction, DNA damage, anterior horn motor neurons, transgenic mouse model, pathogenesis
MeSH terms
Amyotrophic Lateral Sclerosis, Animals, Behavior, Animal, Binding Sites, Brain, DNA-Binding Proteins, Humans, Mice, Transgenic, Motor Neurons, Nerve Degeneration, Phenotype, Virus Activation, Motor Neuron Disease, Endogenous Retroviruses, Terminal Repeat Sequences

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