ArticleScientific reports2016
Activation of innate antiviral immune response via double-stranded RNA-dependent RLR receptor-mediated necroptosis.
Article in Scientific reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 17 citations in OpenAlex.
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- Synthetic double-stranded RNA in antiviral immunity and vaccine adjuvant: insights into poly(I:C) and poly(A:U).Frontiers in immunology · 2026Review
- Red Blood Cell Membrane Vesicles for siRNA Delivery: A Biocompatible Carrier With Passive Tumor Targeting and Prolonged Plasma Residency.International journal of nanomedicine · 2025Article
- Human Melanoma and Glioblastoma Cells Express Cathepsins Supporting Reovirus Moscow Strain Infection.Viruses · 2024Article
- Evaluation of the TLR3 involvement during Schistosoma japonicum-induced pathology.BMC immunology · 2024Article
- Immune evasion of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2); molecular approaches.Molecular immunology · 2023Review
- Native RNA Purification Method for Small RNA Molecules Based on Asymmetrical Flow Field-Flow Fractionation.Pharmaceuticals (Basel, Switzerland) · 2022Article
- Opposite Effects of Apoptotic and Necroptotic Cellular Pathways on Rotavirus Replication.Journal of virology · 2022Article
- Formation of Double Stranded RNA Provokes Smooth Muscle Contractions and Structural Modifications in Bladder Ischemia.Research and reports in urology · 2022Article
- The role of lysosome in regulated necrosis.Acta pharmaceutica Sinica. B · 2020Review
- Trial watch: TLR3 agonists in cancer therapy.Oncoimmunology · 2020Review
- Neuroprotective Effects of Necrostatin-1 Against Oxidative Stress-Induced Cell Damage: an Involvement of Cathepsin D Inhibition.Neurotoxicity research · 2020Article
- Analysis of tick-borne encephalitis virus-induced host responses in human cells of neuronal origin and interferon-mediated protection.The Journal of general virology · 2017Article
- Pore-forming toxin-mediated ion dysregulation leads to death receptor-independent necroptosis of lung epithelial cells during bacterial pneumonia.Cell death and differentiation · 2017Article
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 2 countries.
Funding
Abstract
Viruses induce double-stranded RNA (dsRNA) in the host cells. The mammalian system has developed dsRNA-dependent recognition receptors such as RLRs that recognize the long stretches of dsRNA as PAMPs to activate interferon-mediated antiviral pathways and apoptosis in severe infection. Here we report an efficient antiviral immune response through dsRNA-dependent RLR receptor-mediated necroptosis against infections from different classes of viruses. We demonstrated that virus-infected A549 cells were efficiently killed in the presence of a chimeric RLR receptor, dsCARE. It measurably suppressed the interferon antiviral pathway but promoted IL-1β production. Canonical cell death analysis by morphologic assessment, phosphatidylserine exposure, caspase cleavage and chemical inhibition excluded the involvement of apoptosis and consistently suggested RLR receptor-mediated necroptosis as the underlying mechanism of infected cell death. The necroptotic pathway was augmented by the formation of RIP1-RIP3 necrosome, recruitment of MLKL protein and the activation of cathepsin D. Contributing roles of RIP1 and RIP3 were confirmed by gene knockdown. Furthermore, the necroptosis inhibitor necrostatin-1 but not the pan-caspase inhibitor zVAD impeded dsCARE-dependent infected cell death. Our data provides compelling evidence that the chimeric RLR receptor shifts the common interferon antiviral responses of infected cells to necroptosis and leads to rapid death of the virus-infected cells. This mechanism could be targeted as an efficient antiviral strategy.
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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.