ArticleProceedings of the National Academy of Sciences of the United States of America2025
SARS-CoV-2 infection induces ZBP1-dependent PANoptosis in bystander cells.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers, 1 of them a synthesis that pooled it.
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Who cites it
27 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Programmed cell death in human respiratory syncytial virus infection.Frontiers in cellular and infection microbiology · 2025Pooled it
- Autophagy determines the fate of immune cells by regulating metabolic remodeling and PANoptosis (Review).International journal of molecular medicine · 2026Review
- Innate immune sensors of inflammasomes and PANoptosomes: structural-mechanistic insights and therapeutic implications.Cell research · 2026Review
- The Role of cGAS-STING-Driven PANoptosis in Neurodegenerative Diseases and Therapeutic Prospects.Cells · 2026Review
- Single-cell evidence for PANoptosome complexes.Nature reviews. Molecular cell biology · 2026Article
- The role of inflammatory cell death in type 1 dominant inflammatory skin diseases.Journal der Deutschen Dermatologischen Gesellschaft = Journal of the German Society of Dermatology : JDDG · 2026Review
- PANoptosis in life and death across cell types: From innate immunity to therapeutic implications.Cell chemical biology · 2026Review
- Decoding PANoptosis: Crosstalk of cell death pathways in immunity and inflammation.Immunologic research · 2026Review
- Programmed Cell Death in Chronic Rhinosinusitis.Clinical and translational allergy · 2026Review
- Defining critical roles for ZBP1 in PANoptosis utilizing a novel genetic tool for disease modeling and therapeutic development.bioRxiv : the preprint server for biology · 2026Article
- Article
- Extracellular cGAMP in health and disease.Molecular biomedicine · 2026Review
- Neu1 inhibition restrains BCoV replication and modulates ZBP1-dependent PANoptosis.Veterinary research · 2026Article
- Nlrp12-driven PANoptosis exacerbates liver injury in ConA-induced autoimmune hepatitis.Genes and immunity · 2026Article
- STING-STAT1-ZBP1 axis orchestrates PANoptotic signaling in ischemia-reperfusion induced acute kidney injury.Cell communication and signaling : CCS · 2026Article
- Pseudorabies Virus Infection Triggers PANoptosis to Enhance Inflammatory Responses Both In Vitro and In Vivo.Microorganisms · 2026Article
- ADAR1: a central regulator of dsRNA sensing in host-virus interactions.Frontiers in immunology · 2026Review
- cGAS-STING and PANoptosis: Interplay, Underlying Mechanisms, and Therapeutic Targets.Drug design, development and therapy · 2026Review
- ZBP1 as a dynamic monitor of viral replication: implications for therapeutic strategies.Frontiers in cellular and infection microbiology · 2026Review
- ZBP1 contributes to IFN-β-induced PANoptosis-related skeletal muscle cell injury in dermatomyositis.Frontiers in immunology · 2026Article
Corrections and comments
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Authors and funding
7 authors.
Funding
Abstract
Virus-induced excessive inflammatory response is a key contributor to pathology in respiratory viral infections. However, the underlying mechanisms by which viral infection provokes intense inflammatory reaction and how sustained inflammation leads to tissue damage are not fully understood. Using severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection as an example, our research demonstrates that SARS-CoV-2 infection can induce PANoptosis in bystander cells, contributing to the persistence of inflammatory responses. Specifically, the activation of cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) in infected cells leads to the secretion of 2'3'cGMP-AMP, TNF-α, and IFN-β. These molecules activate STING-induced autophagy-mediated ADAR1 degradation, resulting in the accumulation of Z-nucleic acid, which subsequently triggers ZBP1-dependent PANoptosis in bystander cells. Additionally, inhibiting the cGAS pathway or knocking out STING effectively reduces PANoptosis and alleviates the pathology associated with SARS-CoV-2 and influenza A virus infection in mouse models. Overall, our findings reveal the unexpected role of PANoptosis in bystander cells during SARS-CoV-2 infection as a mechanism driving pathological damage and persistent inflammatory responses. Targeting this process may offer a promising strategy to mitigate tissue damage in COVID-19 as well as other viral infections and inflammatory conditions.
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