ArticlePLoS pathogens2014
Modified vaccinia virus Ankara triggers type I IFN production in murine conventional dendritic cells via a cGAS/STING-mediated cytosolic DNA-sensing pathway.
Article in PLoS pathogens, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 107 papers.
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Who cites it
107 citing papers in PubMed, 170 citations in OpenAlex.
- Molecular mechanism of 2',3'-cGAMP degradation by monkeypox virus poxin-schlafen protein.The Journal of biological chemistry · 2026Article
- Antiviral innate immunity and adaptive immune responses against monkeypox and viral immune evasion.World journal of virology · 2026Review
- Non-cytolytic re-engineering of a viral vaccine vector enables durable effector-memory T cell immunity by reinforcing type I IFN induction.Molecular therapy. Nucleic acids · 2026Article
- Insights into Monkeypox Virus: Host Immunity, Viral Immune Evasion, Recent Advances in Vaccines, Therapeutic Development, and Future Perspectives.Microorganisms · 2026Review
- Treatment sequence of stem cell delivered heterologous oncolytic virus impact on tumor microenvironment in immunocompetent ovarian cancer model.Frontiers in immunology · 2026Article
- Vaccinia virus for lung cancer therapy: preclinical progress and prospects as a systemic immunotherapy platform.Frontiers in immunology · 2026Review
- Mpox virus poxin-schlafen fusion protein suppresses innate antiviral response by sequestering STAT2.Emerging microbes & infections · 2025Article
- Review
- STING-mediated antiviral response: insights into MVA replication control in avian cells.Microbiology spectrum · 2025Article
- The tegument protein VP22 of pseudorabies virus inhibits cGAS condensation by inducing nuclear-to-cytoplasmic translocation of DDX21.PLoS pathogens · 2025Article
- MPXV infection activates cGAS-STING signaling and IFN-I treatment reduces pathogenicity of mpox in CAST/EiJ mice and rhesus macaques.Cell reports. Medicine · 2025Article
- Double-stranded RNA orbivirus disrupts the DNA-sensing cGAS-sting axis to prevent type I IFN induction.Cellular and molecular life sciences : CMLS · 2025Article
- DNA PAMPs as Molecular Tools for the cGAS-STING Signaling Pathways.Methods in molecular biology (Clifton, N.J.) · 2025Article
- The unique immune evasion mechanisms of the mpox virus and their implication for developing new vaccines and immunotherapies.Virologica Sinica · 2024Review
- The monkeypox virus-host interplays.Cell insight · 2024Review
- Poxin-deficient poxviruses are sensed by cGAS prior to genome replication.The Journal of general virology · 2024Article
- cGAS activation in classical dendritic cells causes autoimmunity in TREX1-deficient mice.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Multi-omics characterization of the monkeypox virus infection.Nature communications · 2024Article
- Vaccinia Virus: Mechanisms Supporting Immune Evasion and Successful Long-Term Protective Immunity.Viruses · 2024Review
- Article
47 more citing papers are in PubMed but not listed here.
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Authors and funding
12 authors at 4 institutions in 2 countries.
Funding
Abstract
Modified vaccinia virus Ankara (MVA) is an attenuated poxvirus that has been engineered as a vaccine against infectious agents and cancers. Our goal is to understand how MVA modulates innate immunity in dendritic cells (DCs), which can provide insights to vaccine design. In this study, using murine bone marrow-derived dendritic cells, we assessed type I interferon (IFN) gene induction and protein secretion in response to MVA infection. We report that MVA infection elicits the production of type I IFN in murine conventional dendritic cells (cDCs), but not in plasmacytoid dendritic cells (pDCs). Transcription factors IRF3 (IFN regulatory factor 3) and IRF7, and the positive feedback loop mediated by IFNAR1 (IFN alpha/beta receptor 1), are required for the induction. MVA induction of type I IFN is fully dependent on STING (stimulator of IFN genes) and the newly discovered cytosolic DNA sensor cGAS (cyclic guanosine monophosphate-adenosine monophosphate synthase). MVA infection of cDCs triggers phosphorylation of TBK1 (Tank-binding kinase 1) and IRF3, which is abolished in the absence of cGAS and STING. Furthermore, intravenous delivery of MVA induces type I IFN in wild-type mice, but not in mice lacking STING or IRF3. Treatment of cDCs with inhibitors of endosomal and lysosomal acidification or the lysosomal enzyme Cathepsin B attenuated MVA-induced type I IFN production, indicating that lysosomal enzymatic processing of virions is important for MVA sensing. Taken together, our results demonstrate a critical role of the cGAS/STING-mediated cytosolic DNA-sensing pathway for type I IFN induction in cDCs by MVA. We present evidence that vaccinia virulence factors E3 and N1 inhibit the activation of IRF3 and the induction of IFNB gene in MVA-infected cDCs.
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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.