ArticleThe Journal of clinical investigation2021
Brain immune cells undergo cGAS/STING-dependent apoptosis during herpes simplex virus type 1 infection to limit type I IFN production.
Article in The Journal of clinical investigation, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 83 papers.
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Who cites it
83 citing papers in PubMed, 110 citations in OpenAlex.
- The cGAS-STING Pathway: A Double-Edged Regulator of Neuroinflammation and Myelin Regeneration.Molecular neurobiology · 2026Review
- Effects of Kongsheng Zhenzhong Pills on Neuroinflammation and cGAS-STING Pathway Activity in BV-2 Microglia.Biomedicines · 2026Article
- Alpha-herpesvirus UL55 synergizes with ICP27 to suppress type I interferon production through conserved and host-adapted mechanisms.Journal of virology · 2026Article
- Dysfunctional Mitochondria in Microglia Drive Cognitive Aging and Neurodegeneration via cGAS-STING.Neuroscience bulletin · 2026Article
- Cepharanthine hydrochloride alleviates herpesvirus encephalitis by inhibiting Nrf2 degradation.Virologica Sinica · 2026Article
- Article
- Unmasking the hidden catalyst: How infections trigger Alzheimer's disease.Journal of Alzheimer's disease : JAD · 2026Review
- Role for NF-κB in herpes encephalitis pathology in mice genocopying an inborn error of IRF3-IFN immunity.The Journal of experimental medicine · 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
- Role for NF-κB in herpes encephalitis pathology in mice genocopying an inborn error of IRF3-IFN immunity.The Journal of experimental medicine · 2026Article
- A Novel FGFR3-Targeting Antibody-Drug Conjugate Induces Tumor Cell Apoptosis through the cGAS-STING Pathway in Bladder Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- From infection to dysfunction: viral triggers and antiviral immune factors in Alzheimer's disease pathology.Frontiers in immunology · 2026Review
- NINJ1 blocks HSV-1 entry into macrophages to impact viral replication and immunity.EMBO reports · 2026Article
- The cell-mediated adaptive immune response to herpes simplex virus type 1 encephalitis: mechanisms and clinical implications.Frontiers in immunology · 2026Review
- Herpes simplex virus infection and Alzheimer's disease.Frontiers in aging neuroscience · 2026Review
- HSV-1 infections of the prefrontal cortex: regional vulnerability, cellular mechanisms, and neurocognitive consequences.Frontiers in cellular neuroscience · 2026Review
- The Immunogenic Role of Self-DNA in T Cell Immunity.Clinical reviews in allergy & immunology · 2025Review
- STING agonists trigger monocyte death via apoptosis, pyroptosis, caspase-8 activation and mitochondrial dysfunction.Cell death discovery · 2025Article
- STING activates ZBP1-mediated PANoptosis to defend against HSV-1 retinal infection.Journal of neuroinflammation · 2025Article
- The Path Towards Effective Long-Lasting Tissue-Targeted Prime/Pull/Keep Herpes Simplex Therapeutic Vaccines.Vaccines · 2025Review
23 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
21 authors at 6 institutions in 7 countries.
Funding
Abstract
Protection of the brain from viral infections involves the type I IFN (IFN-I) system, defects in which render humans susceptible to herpes simplex encephalitis (HSE). However, excessive cerebral IFN-I levels lead to pathologies, suggesting the need for tight regulation of responses. Based on data from mouse models, human HSE cases, and primary cell culture systems, we showed that microglia and other immune cells undergo apoptosis in the HSV-1-infected brain through a mechanism dependent on the cyclic GMP-AMP synthase/stimulator of interferon genes (cGAS/STING) pathway, but independent of IFN-I. HSV-1 infection of microglia induced cGAS-dependent apoptosis at high viral doses, whereas lower viral doses led to IFN-I responses. Importantly, inhibition of caspase activity prevented microglial cell death and augmented IFN-I responses. Accordingly, HSV-1-infected organotypic brain slices or mice treated with a caspase inhibitor exhibited lower viral load and an improved infection outcome. Collectively, we identify an activation-induced apoptosis program in brain immune cells that downmodulates local immune responses.
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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.