ArticleVirologica Sinica2024
Ancient dormant virus remnant ERVW-1 drives ferroptosis via degradation of GPX4 and SLC3A2 in schizophrenia.
Article in Virologica Sinica, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 23 citations in OpenAlex.
- Iron dyshomeostasis and its neurobiological mechanisms in psychiatric disorders.Molecular psychiatry · 2026Review
- Transcriptional landscapes of dengue patients reveal associations between HERV activity and disease severity.NAR molecular medicine · 2026Article
- TARDBP Mediates the MAP3K11/SLC3A2/GPX4 Axis in Alzheimer's Disease Rats by Enhancing KRAS mRNA Stability.Journal of cellular and molecular medicine · 2026Article
- ERVWE1 Impairs Mitochondrial Homeostasis and Promotes Neuronal Apoptosis via the miR-27b-3p/BNIP3 Axis in Schizophrenia.Viruses · 2026Article
- Research progress on the regulation of ferroptosis in NPC (Review).Oncology reports · 2026Review
- Recent progress in understanding ferroptosis mechanisms in infectious diseases.Frontiers in cellular and infection microbiology · 2026Review
- Targeting glutathione peroxidase 4 in ferroptosis: from immune regulation to pharmacological development and translational applications.Frontiers in pharmacology · 2026Review
- Review
- The relationship between HERVs and exogenous viral infections: A focus on the value of HERVs in disease prediction and treatment.Virulence · 2025Review
- A study on the transcriptional characteristics of novel HERV gene in the blood of children with Kawasaki disease and its correlation with the disease.Microbiology spectrum · 2025Article
- Unravelling the Viral Hypothesis of Schizophrenia: A Comprehensive Review of Mechanisms and Evidence.International journal of molecular sciences · 2025Review
- African swine fever virus A151R downregulates cGAS-STING-mediated IFN-β production by promoting lipid peroxidation through ferritinophagy-induced ferroptosis.Cellular and molecular life sciences : CMLS · 2025Article
- Human endogenous retrovirus W family envelope protein (ERVWE1) regulates macroautophagy activation and micromitophagy inhibition via NOXA1 in schizophrenia.Virologica Sinica · 2025Article
- Retrotransposon: an insight into neurological disorders from perspectives of neurodevelopment and aging.Translational neurodegeneration · 2025Review
- Ferroptosis in schizophrenia: Mechanisms and therapeutic potentials (Review).Molecular medicine reports · 2025Review
- Neuroimaging stratification reveals the striatal vulnerability to stress as a risk for schizophrenia.Translational psychiatry · 2025Article
- The role of ferroptosis and oxidative stress in cognitive deficits among chronic schizophrenia patients: a multicenter investigation.Schizophrenia (Heidelberg, Germany) · 2025Article
- HERV-W Env Induces Neuron Pyroptosis via the NLRP3-CASP1-GSDMD Pathway in Recent-Onset Schizophrenia.International journal of molecular sciences · 2025Article
- Human endogenous retroviruses in schizophrenia: clinical evidence, molecular mechanisms, and implications.Frontiers in cellular and infection microbiology · 2025Review
- Ancestral retrovirus envelope protein ERVWE1 upregulates circ_0001810, a potential biomarker for schizophrenia, and induces neuronal mitochondrial dysfunction via activating AK2.Cell & bioscience · 2024Article
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Human endogenous retroviruses (HERVs) are remnants of retroviral infections in human germline cells from millions of years ago. Among these, ERVW-1 (also known as HERV-W-ENV, ERVWE1, or ENVW) encodes the envelope protein of the HERV-W family, which contributes to the pathophysiology of schizophrenia. Additionally, neuropathological studies have revealed cell death and disruption of iron homeostasis in the brains of individuals with schizophrenia. Here, our bioinformatics analysis showed that differentially expressed genes in the human prefrontal cortex RNA microarray dataset (GSE53987) were mainly related to ferroptosis and its associated pathways. Clinical data demonstrated significantly lower expression levels of ferroptosis-related genes, particularly Glutathione peroxidase 4 (GPX4) and solute carrier family 3 member 2 (SLC3A2), in schizophrenia patients compared to normal controls. Further in-depth analyses revealed a significant negative correlation between ERVW-1 expression and the levels of GPX4/SLC3A2 in schizophrenia. Studies indicated that ERVW-1 increased iron levels, malondialdehyde (MDA), and transferrin receptor protein 1 (TFR1) expression while decreasing glutathione (GSH) levels and triggering the loss of mitochondrial membrane potential, suggesting that ERVW-1 can induce ferroptosis. Ongoing research has shown that ERVW-1 reduced the expression of GPX4 and SLC3A2 by inhibiting their promoter activities. Moreover, Ferrostatin-1 (Fer-1), the ferroptosis inhibitor, reversed the iron accumulation and mitochondrial membrane potential loss, as well as restored the expressions of ferroptosis markers GSH, MDA, and TFR1 induced by ERVW-1. In conclusion, ERVW-1 could promote ferroptosis by downregulating the expression of GPX4 and SLC3A2, revealing a novel mechanism by which ERVW-1 contributes to neuronal cell death in schizophrenia.
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