ArticleJournal of immunology (Baltimore, Md. : 1950)2014
SARS-coronavirus open reading frame-9b suppresses innate immunity by targeting mitochondria and the MAVS/TRAF3/TRAF6 signalosome.
Article in Journal of immunology (Baltimore, Md. : 1950), 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04397172 (Characterization of ARDS, Critical Illness Myopathy and Their Long-term Consequences in Patients With Covid-19 Disease), which is not on this map. Cited by 324 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Characterization of ARDS, Critical Illness Myopathy and Their Long-term Consequences in Patients With Covid-19 Disease: Effects of Inflammation, Mitochondrial Dysfunction and Plasma Concentrations of Various Sedative Drugs
Who cites it
324 citing papers in PubMed, 490 citations in OpenAlex.
- Exploring Key Regulators of Mitochondrial Dynamics and Immune Response in SARS-CoV-2 Infection.Viruses · 2026Article
- Induction of mitochondrial fission and mtDNA leakage via the Smad3/Drp1 axis by PEDV infection activates the TLR9/NF-κB/IL-1β inflammatory pathway.Virologica Sinica · 2026Article
- Modulation of Host Innate Immune Response by Highly Pathogenic Human Coronaviruses during Viral Infection.Journal of microbiology and biotechnology · 2026Review
- N6-methyladenosine modification of FZR1 mRNA positively regulates antiviral innate immunity by targeting the MAVS-TRAF3/6 axis.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- The Role of Immunosenescence and Inflammaging in the Susceptibility of Older Adults to SARS-CoV-2 Infection.Current pharmaceutical biotechnology · 2026Review
- Mitochondrial quality control: a new mechanism for antiviral therapy.Frontiers in immunology · 2026Review
- Heterologous expression of HCoV-HKU1 ORF 7b by mouse hepatitis virus protects against severe disease during murine infection.PLoS pathogens · 2025Article
- The bittersweet link between glucose metabolism, cellular microenvironment and viral infection.Virulence · 2025Review
- Brucella abortus induces dynamin-related protein 1 (DRP1)-dependent mitochondrial fission in infected macrophages via stress sensor IRE1α altering metabolic function.Journal of immunology (Baltimore, Md. : 1950) · 2025Article
- Article
- Mitochondrial Reactive Oxygen Species: A Unifying Mechanism in Long COVID and Spike Protein-Associated Injury: A Narrative Review.Biomolecules · 2025Review
- Pattern Recognition Receptors (PRRs) Expression and Activation in COVID-19 and Long COVID: From SARS-CoV-2 Escape Mechanisms to Emerging PRR-Targeted Immunotherapies.Microorganisms · 2025Review
- Shaping Viral Infection Outcomes via Organelle Remodeling.Annual review of virology · 2025Review
- Comparative immunological study of Plasmodium knowlesi infections in humans and macaques: insights into cytokine dynamics.Malaria journal · 2025Article
- Pattern recognition receptors: function, regulation and therapeutic potential.Signal transduction and targeted therapy · 2025Review
- Understanding the mechanisms of mitochondrial rewiring during viral infections.The Journal of general virology · 2025Review
- Mitochondrial haplogroup A2 is associated with increased COVID-19 mortality in an admixed Brazilian population.Scientific reports · 2025Article
- Anti-interferon armamentarium of human coronaviruses.Cellular and molecular life sciences : CMLS · 2025Review
- Betacoronavirus internal protein: role in immune evasion and viral pathogenesis.Journal of virology · 2025Review
- The Essential Role of Mitochondrial Dynamics in Viral Infections.International journal of molecular sciences · 2025Review
264 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 4 institutions in 1 country.
Funding
Abstract
Coronaviruses (CoV) have recently emerged as potentially serious pathogens that can cause significant human morbidity and death. The severe acute respiratory syndrome (SARS)-CoV was identified as the etiologic agent of the 2002-2003 international SARS outbreak. Yet, how SARS evades innate immune responses to cause human disease remains poorly understood. In this study, we show that a protein encoded by SARS-CoV designated as open reading frame-9b (ORF-9b) localizes to mitochondria and causes mitochondrial elongation by triggering ubiquitination and proteasomal degradation of dynamin-like protein 1, a host protein involved in mitochondrial fission. Also, acting on mitochondria, ORF-9b targets the mitochondrial-associated adaptor molecule MAVS signalosome by usurping PCBP2 and the HECT domain E3 ligase AIP4 to trigger the degradation of MAVS, TRAF3, and TRAF 6. This severely limits host cell IFN responses. Reducing either PCBP2 or AIP4 expression substantially reversed the ORF-9b-mediated reduction of MAVS and the suppression of antiviral transcriptional responses. Finally, transient ORF-9b expression led to a strong induction of autophagy in cells. The induction of autophagy depended upon ATG5, a critical autophagy regulator, but the inhibition of MAVS signaling did not. These results indicate that SARS-CoV ORF-9b manipulates host cell mitochondria and mitochondrial function to help evade host innate immunity. This study has uncovered an important clue to the pathogenesis of SARS-CoV infection and illustrates the havoc that a small ORF can cause in cells.
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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.