ArticleiScience2023
The SARS-CoV-2 protein ORF3c is a mitochondrial modulator of innate immunity.
Article in iScience, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 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.
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Who cites it
22 citing papers in PubMed, 26 citations in OpenAlex.
- SARS-CoV-2 Infection-Induced Alterations in ADAR Editing Patterns Differ Between Patients Who Developed Critical Compared to Non-Critical COVID-19.International journal of molecular sciences · 2026Article
- Targeting SARS-CoV-2 Structural and Accessory Proteins: Emerging Opportunities for Small-Molecule Coronavirus Antivirals.Pharmaceutics · 2026Review
- Modulation of Host Innate Immune Response by Highly Pathogenic Human Coronaviruses during Viral Infection.Journal of microbiology and biotechnology · 2026Review
- Potential causal role of mitochondrial biological effects in COVID-19: Evidence from Mendelian randomization study.Medicine · 2026Article
- Mechanisms of Mitochondrial Impairment by SARS-CoV-2 Proteins: A Nexus of Pathogenesis with Significant Biochemical and Clinical Implications.International journal of molecular sciences · 2025Review
- SARS-CoV-2-derived RNA replicons as safe and effective vaccines.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- SLIRP amplifies antiviral signaling via positive feedback regulation and contributes to autoimmune diseases.Cell reports · 2025Article
- SARS-CoV-2 infection primes cross-protective respiratory IgA in a MyD88- and MAVS-dependent manner.NPJ vaccines · 2025Article
- Examining the feasibility of replacing ORF3a with fluorescent genes to construct SARS-CoV-2 reporter viruses.The Journal of general virology · 2025Article
- Dynamic Cellular Proteome Remodeling during SARS-CoV-2 Infection. Identification of Plasma Protein Readouts.Journal of proteome research · 2025Article
- Innate immunity in tumors: roles and therapeutic targets.Frontiers in immunology · 2025Review
- Analysis of phosphomotifs coupled to phosphoproteome and interactome unveils potential human kinase substrate proteins in SARS-CoV-2.Frontiers in cellular and infection microbiology · 2025Article
- The innate immune response in SARS-CoV2 infection: focus on toll-like receptor 4 in severe disease outcomes.Frontiers in immunology · 2025Review
- Hidden players of COVID-19: the evolving roles of SARS-CoV-2 accessory proteins.Frontiers in immunology · 2025Review
- Review
- Mitochondrial dysfunction in long COVID: mechanisms, consequences, and potential therapeutic approaches.GeroScience · 2024Review
- SARS-CoV-2 biology and host interactions.Nature reviews. Microbiology · 2024Review
- Article
- SARS-CoV-2 and innate immunity: the good, the bad, and the "goldilocks".Cellular & molecular immunology · 2024Review
- The HLA-II immunopeptidome of SARS-CoV-2.Cell reports · 2024Article
Corrections and comments
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Authors and funding
22 authors at 6 institutions in 3 countries.
Funding
Abstract
The SARS-CoV-2 genome encodes a multitude of accessory proteins. Using comparative genomic approaches, an additional accessory protein, ORF3c, has been predicted to be encoded within the ORF3a sgmRNA. Expression of ORF3c during infection has been confirmed independently by ribosome profiling. Despite ORF3c also being present in the 2002-2003 SARS-CoV, its function has remained unexplored. Here we show that ORF3c localizes to mitochondria, where it inhibits innate immunity by restricting IFN-β production, but not NF-κB activation or JAK-STAT signaling downstream of type I IFN stimulation. We find that ORF3c is inhibitory after stimulation with cytoplasmic RNA helicases RIG-I or MDA5 or adaptor protein MAVS, but not after TRIF, TBK1 or phospho-IRF3 stimulation. ORF3c co-immunoprecipitates with the antiviral proteins MAVS and PGAM5 and induces MAVS cleavage by caspase-3. Together, these data provide insight into an uncharacterized mechanism of innate immune evasion by this important human pathogen.
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What OpenQuestion holds
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.