ArticleThe EMBO journal2023
ER stress induces caspase-2-tBID-GSDME-dependent cell death in neurons lytically infected with herpes simplex virus type 2.
Article in The EMBO journal, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers, 1 of them a synthesis that pooled it.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
19 citing papers in PubMed, 1 synthesis or guideline pooled it, 18 citations in OpenAlex.
- Pyroptosis in Peripheral Neuropathy: From Molecular Mechanisms to Therapeutic Targeting.CNS neuroscience & therapeutics · 2026Pooled it
- HIGH DOSE GAMMAHERPESVIRUS INFECTION IN MACROPHAGES RESULTS IN INFLAMMATORY MULTIMODAL CELL DEATH.bioRxiv : the preprint server for biology · 2026Article
- Cell death network regulation in HSV infection: immune evasion versus host defense.Apoptosis : an international journal on programmed cell death · 2026Review
- Endoplasmic Reticulum Stress-Induced Endothelial Cell Pyroptosis Contributes to Pulmonary Vascular Remodeling and Pulmonary Arterial Hypertension via IRE1α/Caspase-3/GSDME Pathway.Journal of the American Heart Association · 2026Article
- The challenge of cell death switching in inflammasome-targeted therapies for bacterial and viral infections.Communications biology · 2026Review
- Herpes simplex virus type 2 encephalitis in critically ill adults: A retrospective analysis of EURECA and Herpetics cohort studies.Critical care (London, England) · 2026Article
- Role for NF-κB in herpes encephalitis pathology in mice genocopying an inborn error of IRF3-IFN immunity.The Journal of experimental medicine · 2026Article
- Oncolytic virus and immunogenic cell death in cancer therapy.Tumour virus research · 2025Review
- Pyroptosis: inflammatory cell death mechanism and its pathological roles in neurological diseases and injuries.Apoptosis : an international journal on programmed cell death · 2025Review
- ATG7 in innate immune cells is required for host defense against nontuberculous mycobacterial pulmonary infections.Nature communications · 2025Article
- Pyroptosis, a double-edged sword during pathogen infection: a review.Cell death discovery · 2025Review
- Mechanistic insights into gasdermin-mediated pyroptosis.Nature reviews. Molecular cell biology · 2025Review
- Hantaan virus infection induces human mucosal-associated invariant T cell pyroptosis through IRE1α pathway.Communications biology · 2025Article
- Bid Protein: A Participant in the Apoptotic Network with Roles in Viral Infections.International journal of molecular sciences · 2025Review
- Role of VDAC1 in hepatocyte apoptosis during acute liver injury in rats induced by obstructive jaundice.Iranian journal of basic medical sciences · 2025Article
- Differentiation of Human Neurons and Neuron-Like Cells to Study VZV Neuronal Infection.Methods in molecular biology (Clifton, N.J.) · 2025Article
- Mechanisms of ferroptosis and the relationship between ferroptosis and ER stress after JEV and HSV infection.Frontiers in microbiology · 2024Review
- Advances in research on the impact and mechanisms of pathogenic microorganism infections on pyroptosis.Frontiers in microbiology · 2024Review
- ER stress induces caspase-2-tBID-GSDME-dependent cell death in neurons lytically infected with herpes simplex virus type 2.The EMBO journal · 2023Article
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 3 countries.
Funding
Abstract
Neurotropic viruses, including herpes simplex virus (HSV) types 1 and 2, have the capacity to infect neurons and can cause severe diseases. This is associated with neuronal cell death, which may contribute to morbidity or even mortality if the infection is not controlled. However, the mechanistic details of HSV-induced neuronal cell death remain enigmatic. Here, we report that lytic HSV-2 infection of human neuron-like SH-SY5Y cells and primary human and murine brain cells leads to cell death mediated by gasdermin E (GSDME). HSV-2-induced GSDME-mediated cell death occurs downstream of replication-induced endoplasmic reticulum stress driven by inositol-requiring kinase 1α (IRE1α), leading to activation of caspase-2, cleavage of the pro-apoptotic protein BH3-interacting domain death agonist (BID), and mitochondria-dependent activation of caspase-3. Finally, necrotic neurons released alarmins, which activated inflammatory responses in human iPSC-derived microglia. In conclusion, lytic HSV infection in neurons activates an ER stress-driven pathway to execute GSDME-mediated cell death and promote inflammation.
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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 Socratic graph.