ArticleThe Journal of biological chemistry2007
Regulation of IRF-3-dependent innate immunity by the papain-like protease domain of the severe acute respiratory syndrome coronavirus.
Article in The Journal of biological chemistry, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 271 papers, 2 of them syntheses that pooled it.
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Who cites it
271 citing papers in PubMed, 2 syntheses or guidelines pooled it, 418 citations in OpenAlex.
- Time Series Analysis of SARS-CoV-2 Genomes and Correlations among Highly Prevalent Mutations.Microbiology spectrum · 2022Pooled it
- The proteasome as a druggable target with multiple therapeutic potentialities: Cutting and non-cutting edges.Pharmacology & therapeutics · 2020Pooled it
- Interferon-Stimulated Gene-Mediated Defense Against Prion Infection: Noncanonical Function of Oas1a.Viruses · 2026Review
- Cell-autonomous immunity as an integrated immune network against bacterial and viral pathogens.Nature microbiology · 2026Review
- ATG7 Limits Basal Antiviral Gene Expression and Moderately Promotes VSV Replication in Mammalian Non-Immune Cells.Pathogens (Basel, Switzerland) · 2026Article
- YL1004 is a SARS-CoV-2 papain-like protease inhibitor with immunomodulatory and antiviral activity in mice.Nature communications · 2026Article
- Nuclear factor IC promoting porcine reproductive and respiratory syndrome virus (PRRSV) replication and suppressing type I interferon transcription.BMC veterinary research · 2026Article
- Chasing allosteric inhibition of the SARS-CoV-2 PLpro via molecular dynamics simulations with flooding fragments (MDFFr).Journal of computer-aided molecular design · 2025Article
- Article
- Cytokine-independent induction of LGP2/DHX58 in viral infection.The Journal of general virology · 2025Article
- Viral strategies to antagonize the host antiviral innate immunity: an indispensable research direction for emerging virus-host interactions.Emerging microbes & infections · 2024Review
- Flavonoids Derived from the Roots ofPlants (Basel, Switzerland) · 2024Article
- SARS-CoV-2 PLChemistryOpen · 2024Article
- Profiling of coronaviral MProtein science : a publication of the Protein Society · 2024Article
- Viral Factors in Modulation of Host Immune Response: A Route to Novel Antiviral Agents and New Therapeutic Approaches.International journal of molecular sciences · 2024Review
- Viral deubiquitinating proteases and the promising strategies of their inhibition.Virus research · 2024Review
- Mechanism, structural and functional insights into nidovirus-induced double-membrane vesicles.Frontiers in immunology · 2024Review
- Targeting SARS-CoV-2 nonstructural protein 3: Function, structure, inhibition, and perspective in drug discovery.Drug discovery today · 2024Review
- USP2 inhibition prevents infection with ACE2-dependent coronaviruses in vitro and is protective against SARS-CoV-2 in mice.Science translational medicine · 2023Article
- In silico study unfolds inhibitory potential of epicatechin gallate against SARS-CoV-2 entry and replication within the host cell.Mechanobiology in medicine · 2023Article
211 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
11 authors at 5 institutions in 2 countries.
Funding
Abstract
Severe acute respiratory syndrome coronavirus (SARS-CoV) is a novel coronavirus that causes a highly contagious respiratory disease, SARS, with significant mortality. Although factors contributing to the highly pathogenic nature of SARS-CoV remain poorly understood, it has been reported that SARS-CoV infection does not induce type I interferons (IFNs) in cell culture. However, it is uncertain whether SARS-CoV evades host detection or has evolved mechanisms to counteract innate host defenses. We show here that infection of SARS-CoV triggers a weak IFN response in cultured human lung/bronchial epithelial cells without inducing the phosphorylation of IFN-regulatory factor 3 (IRF-3), a latent cellular transcription factor that is pivotal for type I IFN synthesis. Furthermore, SARS-CoV infection blocked the induction of IFN antiviral activity and the up-regulation of protein expression of a subset of IFN-stimulated genes triggered by double-stranded RNA or an unrelated paramyxovirus. In searching for a SARS-CoV protein capable of counteracting innate immunity, we identified the papain-like protease (PLpro) domain as a potent IFN antagonist. The inhibition of the IFN response does not require the protease activity of PLpro. Rather, PLpro interacts with IRF-3 and inhibits the phosphorylation and nuclear translocation of IRF-3, thereby disrupting the activation of type I IFN responses through either Toll-like receptor 3 or retinoic acid-inducible gene I/melanoma differentiation-associated gene 5 pathways. Our data suggest that regulation of IRF-3-dependent innate antiviral defenses by PLpro may contribute to the establishment 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.