ArticleJCI insight2020
Human endogenous retrovirus HERV-K(HML-2) RNA causes neurodegeneration through Toll-like receptors.
Article in JCI insight, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 86 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
86 citing papers in PubMed, 130 citations in OpenAlex.
- An Integrated Analysis of Manganese Metabolism-Related Genes and Their Association With Biomarkers, Immune Infiltration, and Clinical Subtypes in Alzheimer's Disease.Genes, brain, and behavior · 2026Article
- TLR7 in systemic lupus erythematosus: genetics and emerging therapies.Nature reviews. Rheumatology · 2026Review
- Long-read sequencing maps transposable element variation and its regulatory and epigenetic effects in the human brain.bioRxiv : the preprint server for biology · 2026Article
- ERVK activity in CD8Journal of neuroinflammation · 2026Article
- Immune landscape of the affected brain in Rasmussen encephalitis.Scientific reports · 2026Article
- Viral Mimicry of Alzheimer's Disease: Innate Sensing of Self-Nucleic Acids as a Driver of Glial Senescence.Journal of molecular neuroscience : MN · 2026Review
- Downregulation of miRNAs Accompanies Increased HERV-K (HML-2) Expression in Amyotrophic Lateral Sclerosis.Molecular neurobiology · 2026Article
- Sex Differences in Metabolite-Immune Circuits of Neuroinflammation.Immunological reviews · 2026Review
- Implications of virus-induced stress granules in tauopathies.Translational neurodegeneration · 2026Review
- Review
- Epigenetic dysregulation of transposable elements in cognitive impairment and Alzheimer's disease.GeroScience · 2025Article
- Human Endogenous Retroviruses and Diseases.MedComm · 2025Review
- Transposable elements in health and disease: Molecular basis and clinical implications.Chinese medical journal · 2025Review
- Article
- Immune System-Tumor Crosstalk Under Microgravity: Mechanistic Insights, Challenges, and Translational Perspectives.Cancers · 2025Review
- Endogenous Retroviruses in Host-Virus Coevolution: From Genomic Domestication to Functional Innovation.Genes · 2025Review
- Glial reactivity and cognitive decline follow chronic heterochromatin loss in neurons.Nature communications · 2025Article
- Activation of intestinal endogenous retroviruses by alcohol exacerbates liver disease.The Journal of clinical investigation · 2025Article
- Sex differences in adenosine deaminase activity associate with disparities in SARS-CoV-2 innate immunity.iScience · 2025Article
- Neurodegenerative disease-associated microRNAs acting as signaling molecules modulate CNS neuron structure and viability.Cell communication and signaling : CCS · 2025Article
26 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
26 authors at 7 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Although human endogenous retroviruses (HERVs) represent a substantial proportion of the human genome and some HERVs, such as HERV-K(HML-2), are reported to be involved in neurological disorders, little is known about their biological function. We report that RNA from an HERV-K(HML-2) envelope gene region binds to and activates human Toll-like receptor (TLR) 8, as well as murine Tlr7, expressed in neurons and microglia, thereby causing neurodegeneration. HERV-K(HML-2) RNA introduced into the cerebrospinal fluid (CSF) of either C57BL/6 wild-type mice or APPPS1 mice, a mouse model for Alzheimer's disease (AD), resulted in neurodegeneration and microglia accumulation. Tlr7-deficient mice were protected against neurodegenerative effects but were resensitized toward HERV-K(HML-2) RNA when neurons ectopically expressed murine Tlr7 or human TLR8. Transcriptome data sets of human AD brain samples revealed a distinct correlation of upregulated HERV-K(HML-2) and TLR8 RNA expression. HERV-K(HML-2) RNA was detectable more frequently in CSF from individuals with AD compared with controls. Our data establish HERV-K(HML-2) RNA as an endogenous ligand for species-specific TLRs 7/8 and imply a functional contribution of human endogenous retroviral transcripts to neurodegenerative processes, such as AD.
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Registered trials
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.