ArticleCell death & disease2018
SARS-Coronavirus Open Reading Frame-3a drives multimodal necrotic cell death.
Article in Cell death & disease, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 161 papers, 1 of them a synthesis that pooled it.
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Who cites it
161 citing papers in PubMed, 1 synthesis or guideline pooled it, 242 citations in OpenAlex.
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- Nonlytic Egress and Transmission in the Virus World.Annual review of biochemistry · 2025Review
- Dysregulated TFEB-autophagy-lysosome pathway links acute COVID-19 immunopathology to Long COVID sequelae.Frontiers in immunology · 2025Review
- Implementation of an Immunoassay Based on the MVA-T7pol-Expression System for Rapid Identification of Immunogenic SARS-CoV-2 Antigens: A Proof-of-Concept Study.International journal of molecular sciences · 2024Article
- VCP Inhibition Augments NLRP3 Inflammasome Activation.Inflammation · 2024Article
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- An Overview of SARS-CoV-2 Potential Targets, Inhibitors, and Computational Insights to Enrich the Promising Treatment Strategies.Current microbiology · 2024Review
- SARS-CoV-2 and its ORF3a, E and M viroporins activate inflammasome in human macrophages and induce of IL-1α in pulmonary epithelial and endothelial cells.Cell death discovery · 2024Article
- Mitochondria protective and anti-apoptotic effects of peripheral benzodiazepine receptor and its ligands on the treatment of asthma in vitro and vivo.Journal of inflammation (London, England) · 2024Article
- Vitamin D regulates COVID-19 associated severity by suppressing the NLRP3 inflammasome pathway.PloS one · 2024Article
- Interaction between coronaviruses and the autophagic response.Frontiers in cellular and infection microbiology · 2024Review
- The Role of the NRF2 Pathway in the Pathogenesis of Viral Respiratory Infections.Pathogens (Basel, Switzerland) · 2023Review
- SARS-CoV-2 envelope protein induces necroptosis and mediates inflammatory response in lung and colon cells through receptor interacting protein kinase 1.Apoptosis : an international journal on programmed cell death · 2023Article
101 more citing papers are in PubMed but not listed here.
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
Abstract
The molecular mechanisms underlying the severe lung pathology that occurs during SARS-CoV infections remain incompletely understood. The largest of the SARS-CoV accessory protein open reading frames (SARS 3a) oligomerizes, dynamically inserting into late endosomal, lysosomal, and trans-Golgi-network membranes. While previously implicated in a non-inflammatory apoptotic cell death pathway, here we extend the range of SARS 3a pathophysiologic targets by examining its effects on necrotic cell death pathways. We show that SARS 3a interacts with Receptor Interacting Protein 3 (Rip3), which augments the oligomerization of SARS 3a helping drive necrotic cell death. In addition, by inserting into lysosomal membranes SARS 3a triggers lysosomal damage and dysfunction. Consequently, Transcription Factor EB (TFEB) translocates to the nucleus increasing the transcription of autophagy- and lysosome-related genes. Finally, SARS 3a activates caspase-1 either directly or via an enhanced potassium efflux, which triggers NLRP3 inflammasome assembly. In summary, Rip3-mediated oligomerization of SARS 3a causes necrotic cell death, lysosomal damage, and caspase-1 activation-all likely contributing to the clinical manifestations of SARS-CoV infection.
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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.