ArticlePLoS pathogens2020
Varicella zoster virus encodes a viral decoy RHIM to inhibit cell death.
Article in PLoS pathogens, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 62 citations in OpenAlex.
- Biological consequences of Z-nucleic acid sensing by ZBP1 and ADAR1.RNA biology · 2026Review
- Mechanisms, regulation and clinical relevance of necroptosis.Nature reviews. Molecular cell biology · 2026Review
- Functional amyloids as molecular switches: emerging roles in diverse signalling pathways.Biochemical Society transactions · 2026Review
- Review
- De novo cyclic peptides allow visualisation of the monomeric and functional amyloid conformations of the kinase RIPK3.The Biochemical journal · 2026Article
- vIRA Inhibition of Antiviral Necroptosis and RIPK3 Binding Are Separable Events.Pathogens (Basel, Switzerland) · 2026Article
- ZBP1 as a dynamic monitor of viral replication: implications for therapeutic strategies.Frontiers in cellular and infection microbiology · 2026Review
- Innate Immune Sensors and Cell Death-Frontiers Coordinating Homeostasis, Immunity, and Inflammation in Skin.Viruses · 2025Review
- Bat RNA viruses employ viral RHIMs orchestrating species-specific cell death programs linked to Z-RNA sensing and ZBP1-RIPK3 signaling.iScience · 2024Article
- ZBP1 inhibits the replication of Senecavirus A by enhancing NF-κB signaling pathway mediated antiviral response in porcine alveolar macrophage 3D4/21 cells.Cellular & molecular biology letters · 2024Article
- Viruses and amyloids - a vicious liaison.Prion · 2023Review
- Phosphorylation-dependent pseudokinase domain dimerization drives full-length MLKL oligomerization.Nature communications · 2023Article
- The Z-nucleic acid sensor ZBP1 in health and disease.The Journal of experimental medicine · 2023Article
- PANoptosome signaling and therapeutic implications in infection: central role for ZBP1 to activate the inflammasome and PANoptosis.Current opinion in immunology · 2023Review
- The VEGFR/PDGFR tyrosine kinase inhibitor, ABT-869, blocks necroptosis by targeting RIPK1 kinase.The Biochemical journal · 2023Article
- Low complexity domains of the nucleocapsid protein of SARS-CoV-2 form amyloid fibrils.Nature communications · 2023Article
- Programmed Necrosis in Host Defense.Current topics in microbiology and immunology · 2023Article
- ZBP1-Mediated Necroptosis: Mechanisms and Therapeutic Implications.Molecules (Basel, Switzerland) · 2022Review
- ZBP1: A Powerful Innate Immune Sensor and Double-Edged Sword in Host Immunity.International journal of molecular sciences · 2022Review
- Necroptosis at a glance.Journal of cell science · 2022Article
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Authors and funding
11 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Herpesviruses are known to encode a number of inhibitors of host cell death, including RIP Homotypic Interaction Motif (RHIM)-containing proteins. Varicella zoster virus (VZV) is a member of the alphaherpesvirus subfamily and is responsible for causing chickenpox and shingles. We have identified a novel viral RHIM in the VZV capsid triplex protein, open reading frame (ORF) 20, that acts as a host cell death inhibitor. Like the human cellular RHIMs in RIPK1 and RIPK3 that stabilise the necrosome in TNF-induced necroptosis, and the viral RHIM in M45 from murine cytomegalovirus that inhibits cell death, the ORF20 RHIM is capable of forming fibrillar functional amyloid complexes. Notably, the ORF20 RHIM forms hybrid amyloid complexes with human ZBP1, a cytoplasmic sensor of viral nucleic acid. Although VZV can inhibit TNF-induced necroptosis, the ORF20 RHIM does not appear to be responsible for this inhibition. In contrast, the ZBP1 pathway is identified as important for VZV infection. Mutation of the ORF20 RHIM renders the virus incapable of efficient spread in ZBP1-expressing HT-29 cells, an effect which can be reversed by the inhibition of caspases. Therefore we conclude that the VZV ORF20 RHIM is important for preventing ZBP1-driven apoptosis during VZV infection, and propose that it mediates this effect by sequestering ZBP1 into decoy amyloid assemblies.
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