ArticleFASEB journal : official publication of the Federation of American Societies for Experimental Biology2019
Severe acute respiratory syndrome coronavirus ORF3a protein activates the NLRP3 inflammasome by promoting TRAF3-dependent ubiquitination of ASC.
Article in FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 331 papers, 1 of them a synthesis that pooled it.
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331 citing papers in PubMed, 1 synthesis or guideline pooled it, 517 citations in OpenAlex.
- COVID-19 pandemic: the delta variant, T-cell responses, and the efficacy of developing vaccines.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2022Pooled it
- The accessory protein ORF3a hijacks the CLCC1 chloride channel to disrupt ER homeostasis in betacoronavirus pathogenesis.Cell discovery · 2026Article
- ZDHHC18-Mediated Palmitoylation of ORF3a Promotes SARS-CoV-2 Pathogenesis by Antagonizing TRIM16-Mediated Ubiquitination and Proteasomal Degradation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Temporal Dynamics of Innate Immune Activation and Viral Interference During Sequential Co-Infection with Influenza A Virus and SARS-CoV-2: Molecular Mechanisms, Clinical Evidence, and Therapeutic Implications.International journal of molecular sciences · 2026Review
- Modulation of Host Innate Immune Response by Highly Pathogenic Human Coronaviruses during Viral Infection.Journal of microbiology and biotechnology · 2026Review
- TRIM21 facilitates inflammasome assembly and contributes to autoinflammatory disease.Nature communications · 2026Article
- Sensing the spectrum: diverse stimuli for the NLRP3 inflammasome.Communications biology · 2026Review
- NLR Inflammasomes in Viral Infections: From Molecular Mechanisms to Therapeutic Interventions.Viruses · 2026Review
- Macrophage makeover extreme viral edition: mechanisms of immune subversion and therapeutic perspectives.The Journal of general virology · 2026Review
- Cardiovascular sequelae of Long COVID: immune dysregulation inflammation as central drivers.Frontiers in immunology · 2026Review
- Comparative progress on the mechanisms of airway mucosal injury induced by different pathogens: SARS-CoV-2, influenza A virus, and Mycoplasma pneumoniae.Frontiers in cellular and infection microbiology · 2026Review
- ORF3 Depletion Attenuates SADS-CoV Virulence and Retains Partial Maternally Mediated Protection in Suckling Mice.Transboundary and emerging diseases · 2026Article
- Gastrointestinal inflammation and cancer: viral and bacterial interplay.Gut microbes · 2025Review
- Association of RBD mutations with COVID-19 disease severity in the Iranian population.Virus genes · 2025Article
- Article
- Effects ofiMetaOmics · 2025Article
- Activity and cellular distribution of ORF3a mutants of SARS-CoV-2 variants of concern.The Journal of general virology · 2025Article
- SARS-CoV-2 encoded ORF3a interacts with YY1 to promote latent HCMV reactivation.PLoS pathogens · 2025Article
- Potential Predictors of the Outcome of Tocilizumab Treatment in Patients with COVID-19-Associated Hyperinflammation.Infectious diseases & clinical microbiology · 2025Article
- SARS-CoV-2 accessory proteins ORF3a and ORF6 alter the miRNome of human lung epithelial cells.Molecular biology reports · 2025Article
271 more citing papers are in PubMed but not listed here.
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Authors and funding
11 authors at 3 institutions in 2 countries.
Funding
Abstract
Severe acute respiratory syndrome coronavirus (SARS-CoV) is capable of inducing a storm of proinflammatory cytokines. In this study, we show that the SARS-CoV open reading frame 3a (ORF3a) accessory protein activates the NLRP3 inflammasome by promoting TNF receptor-associated factor 3 (TRAF3)-mediated ubiquitination of apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC). SARS-CoV and its ORF3a protein were found to be potent activators of pro-IL-1β gene transcription and protein maturation, the 2 signals required for activation of the NLRP3 inflammasome. ORF3a induced pro-IL-1β transcription through activation of NF-κB, which was mediated by TRAF3-dependent ubiquitination and processing of p105. ORF3a-induced elevation of IL-1β secretion was independent of its ion channel activity or absent in melanoma 2 but required NLRP3, ASC, and TRAF3. ORF3a interacted with TRAF3 and ASC, colocalized with them in discrete punctate structures in the cytoplasm, and facilitated ASC speck formation. TRAF3-dependent K63-linked ubiquitination of ASC was more pronounced in SARS-CoV-infected cells or when ORF3a was expressed. Taken together, our findings reveal a new mechanism by which SARS-CoV ORF3a protein activates NF-κB and the NLRP3 inflammasome by promoting TRAF3-dependent ubiquitination of p105 and ASC.-Siu, K.-L., Yuen, K.-S., Castaño-Rodriguez, C., Ye, Z.-W., Yeung, M.-L., Fung, S.-Y., Yuan, S., Chan, C.-P., Yuen, K.-Y., Enjuanes, L., Jin, D.-Y. Severe acute respiratory syndrome coronavirus ORF3a protein activates the NLRP3 inflammasome by promoting TRAF3-dependent ubiquitination of ASC.
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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.