ArticleJournal of virology2009
Vaccinia virus E3 suppresses expression of diverse cytokines through inhibition of the PKR, NF-kappaB, and IRF3 pathways.
Article in Journal of virology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers.
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Who cites it
56 citing papers in PubMed, 79 citations in OpenAlex.
- Kinetics of serum cytokines after primary or repeat vaccination with the smallpox vaccine.The Journal of infectious diseases · 2010Trial
- Synergistic Oncolytic Effect of HSVtk- and IL-15Rα-Armed Vaccinia Viruses Inducing Systemic Antitumor Immunity.International journal of molecular sciences · 2026Article
- Genome-wide CRISPR/Cas9 screening identifies host factors critical for antiviral defense against equine herpesvirus type 1.Frontiers in immunology · 2026Article
- Review
- Contagious ecthyma in small ruminants: from etiology to vaccine challenges - a review.Veterinary research communications · 2025Review
- The Nucleocapsid Proteins of SARS-CoV-2 and Its Close Relative Bat Coronavirus RaTG13 Are Capable of Inhibiting PKR- and RNase L-Mediated Antiviral Pathways.Microbiology spectrum · 2023Article
- Vaccinia virus BTB-Kelch proteins C2 and F3 inhibit NF-κB activation.The Journal of general virology · 2022Article
- Single Immunization with Recombinant ACAM2000 Vaccinia Viruses Expressing the Spike and the Nucleocapsid Proteins Protects Hamsters against SARS-CoV-2-Caused Clinical Disease.Journal of virology · 2022Article
- A class of viral inducer of degradation of the necroptosis adaptor RIPK3 regulates virus-induced inflammation.Immunity · 2021Article
- Identification of protective T-cell antigens for smallpox vaccines.Cytotherapy · 2020Article
- Review
- Naturally Occurring and Engineered Alphaviruses Sensitive to Double-Stranded-RNA-Activated Protein Kinase Show Restricted Translation in Mammalian Cells, Increased Sensitivity to Interferon, and Marked Oncotropism.Journal of virology · 2020Article
- The Role of the Z-DNA Binding Domain in Innate Immunity and Stress Granules.Frontiers in immunology · 2020Review
- Messenger RNA translation enhancement by immune evasion proteins: a comparative study between EKB (vaccinia virus) and NS1 (influenza A virus).Scientific reports · 2019Article
- Translational control during poxvirus infection.Wiley interdisciplinary reviews. RNA · 2019Review
- Article
- Poxviral protein E3-altered cytokine production reveals that DExD/H-box helicase 9 controls Toll-like receptor-stimulated immune responses.The Journal of biological chemistry · 2018Article
- Review
- A parapoxviral virion protein targets the retinoblastoma protein to inhibit NF-κB signaling.PLoS pathogens · 2017Article
- SPI-2/CrmA inhibits IFN-β induction by targeting TBK1/IKKε.Scientific reports · 2017Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The vaccinia virus double-stranded RNA binding protein E3 has been demonstrated to inhibit the expression of cytokines, including beta interferon (IFN-beta) and tumor necrosis factor alpha (TNF-alpha). However, few details regarding the molecular mechanisms of this inhibition have been described. Using real-time PCR arrays, we found that E3 suppressed the induction of a diverse array of cytokines representing members of the IFN, interleukin (IL), TNF, and transforming growth factor cytokine families. We discovered that the factor(s) responsible for the induction of IL-6, TNF-alpha, and inhibin beta A (INHBA) was associated with the early and late phases of virus infection. In contrast, the factor(s) which regulates IFN-beta induction was associated with the late phase of replication. We have found that expression of these cytokines can be induced by transfection of cells with RNA isolated from vaccinia virus-infected cells. Moreover, we provide evidence that E3 antagonizes both PKR-dependent and PKR-independent pathways to regulate cytokine expression. PKR-dependent activation of p38 and NF-kappaB was required for vaccinia virus-induced INHBA expression, whereas induction of TNF-alpha required only PKR-dependent NF-kappaB activation. In contrast, induction of IL-6 and IFN-beta was largely PKR independent. IL-6 induction is regulated by NF-kappaB, while IFN-beta induction is mediated by IFN-beta promoter stimulator 1 and IFN regulatory factor 3/NF-kappaB. Collectively, these results indicate that E3 suppresses distinct but interlinked host signaling pathways to inhibit the expression of a diverse array of cytokines.
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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.