ArticlePLoS pathogens2022
RIPK3 and caspase 8 collaborate to limit herpes simplex encephalitis.
Article in PLoS pathogens, 2022. 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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The trial behind it
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Who cites it
22 citing papers in PubMed, 29 citations in OpenAlex.
- Z-Nucleic Acid-Binding Protein (ZBP)1 (DAI/DLM1) Regulation in Antiviral Cell Death Pathways.Pathogens (Basel, Switzerland) · 2026Review
- Cell death network regulation in HSV infection: immune evasion versus host defense.Apoptosis : an international journal on programmed cell death · 2026Review
- Time-Course Transcriptomic Analysis Reveals PANoptosis-CCL2 Axis in Herpes Simplex Keratitis.Investigative ophthalmology & visual science · 2026Article
- Article
- Analysis of the Clinical Features of HSV-2 Encephalitis Confirmed by the mNGS Technique: Insights Derived from Seven Patient Studies.Infection and drug resistance · 2026Article
- NINJ1 blocks HSV-1 entry into macrophages to impact viral replication and immunity.EMBO reports · 2026Article
- Astrocytic RIPK3 exerts protective anti-inflammatory activity in mice with viral encephalitis by transcriptional induction of serpins.Science signaling · 2025Article
- Article
- Targeting SARM1 as a novel neuroprotective therapy in neurotropic viral infections.Journal of neuroinflammation · 2025Article
- The kinase RIPK3 promotes neuronal survival by suppressing excitatory neurotransmission during central nervous system viral infection.Immunity · 2025Article
- A Better Understanding of the Clinical and Pathological Changes in Viral Retinitis: Steps to Improve Visual Outcomes.Microorganisms · 2024Review
- Caspase-8 activity mediates TNFα production and restrictsInfection and immunity · 2024Article
- Article
- RIPK3 signaling and its role in regulated cell death and diseases.Cell death discovery · 2024Review
- RIPK3 promotes neuronal survival by suppressing excitatory neurotransmission during CNS viral infection.bioRxiv : the preprint server for biology · 2024Article
- Caspase-8 activity mediates TNFα production and restrictsbioRxiv : the preprint server for biology · 2024Article
- Herpes simplex virus infection induces necroptosis of neurons and astrocytes in human fetal organotypic brain slice cultures.Journal of neuroinflammation · 2024Article
- RIPK3 promotes brain region-specific interferon signaling and restriction of tick-borne flavivirus infection.PLoS pathogens · 2023Article
- The Host-Pathogen Interplay: A Tale of Two Stories within the Cornea and Posterior Segment.Microorganisms · 2023Review
- Programmed Necrosis in Host Defense.Current topics in microbiology and immunology · 2023Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Invasion of the brain by herpes simplex virus 1 (HSV1) can lead to the development of herpes simplex encephalitis (HSE) that is often associated with significant morbidity and mortality regardless of therapeutic intervention. Both virus and host immune factors dictate HSE onset and progression. Because programmed cell death pathways including necroptosis are important antiviral defense mechanisms in HSV1-associated peripheral diseases, they might also play critical roles in HSV1 neuropathogenesis. HSV1-encoded ICP6 prevents receptor-interacting protein kinase 3 (RIPK3)-mediated necroptosis during infection of human cells, but it also acts as a species-dependent inducer of necroptosis in murine cells and thereby restricts virus replication. We therefore used an established mouse model of HSE to investigate RIPK3-mediated necroptosis impact on HSV1 neuropathogenesis. Following corneal HSV1 inoculation, RIPK3 knockout mice showed increased susceptibility to HSE when compared with wildtype mice indicating RIPK3 helps to limit HSE progression. RIPK3-mediated defense against HSE was found to be independent of the kinase domain necessary to drive necroptosis implicating that a death independent function of RIPK3 protects against HSE. Conversely the pro-necroptotic kinase function RIPK3 served to limit viral replication in corneal tissue implicating a tissue-specific RIPK3 function in limiting HSV1. Further evaluation of the kinase-independent mechanism to restrict HSE revealed that the RIPK3 signaling partner, caspase 8, contributes to limiting HSE neuropathogenesis. Increased HSE susceptibility from loss of caspase 8 and RIPK3 correlated with decreased levels of chemokines, cytokines, and antiviral lymphocytes recruitment to the brain. We conclude that RIPK3 contributes toward host control of HSV1 replication in a tissue-specific fashion. Whereas RIPK3-mediated necroptosis restricts virus replication within the cornea, kinase-independent induction of inflammation by RIPK3 in collaboration with caspase 8 restricts virus replication within the brain during HSE neuropathogenesis.
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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.