ArticlePLoS pathogens2011
Induction of Noxa-mediated apoptosis by modified vaccinia virus Ankara depends on viral recognition by cytosolic helicases, leading to IRF-3/IFN-β-dependent induction of pro-apoptotic Noxa.
Article in PLoS pathogens, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 53 citations in OpenAlex.
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- Pandora's Box of AML: HowBiomedicines · 2025Review
- Quantitative proteomics defines mechanisms of antiviral defence and cell death during modified vaccinia Ankara infection.Nature communications · 2023Article
- Subversion of Programed Cell Death by Poxviruses.Current topics in microbiology and immunology · 2023Article
- Poxviruses and the immune system: Implications for monkeypox virus.International immunopharmacology · 2022Review
- Pattern Recognition Receptors of Nucleic Acids Can Cause Sublethal Activation of the Mitochondrial Apoptosis Pathway during Viral Infection.Journal of virology · 2022Article
- Viral-mediated activation and inhibition of programmed cell death.PLoS pathogens · 2022Review
- The BH3-only protein NOXA serves as an independent predictor of breast cancer patient survival and defines susceptibility to microtubule targeting agents.Cell death & disease · 2021Article
- Diversity of cell death signaling pathways in macrophages upon infection with modified vaccinia virus Ankara (MVA).Cell death & disease · 2021Article
- Importance of Bcl-2-family proteins in murine hematopoietic progenitor and early B cells.Cell death & disease · 2021Article
- Cell death signalling in virus infection.Cellular signalling · 2020Review
- MARCH5 requires MTCH2 to coordinate proteasomal turnover of the MCL1:NOXA complex.Cell death and differentiation · 2020Article
- Apoptosis Functions in Defense against Infection of Mammalian Cells with Environmental Chlamydiae.Infection and immunity · 2020Article
- The involvement of regulated cell death forms in modulating the bacterial and viral pathogenesis.International review of cell and molecular biology · 2020Review
- A non-death function of the mitochondrial apoptosis apparatus in immunity.The EMBO journal · 2019Article
- Innate immune sensor laboratory of genetics and physiology 2 suppresses tumor cell growth and functions as a prognostic marker in neuroblastoma.Cancer science · 2018Article
- Expression of the Vaccinia Virus Antiapoptotic F1 Protein Is Blocked by Protein Kinase R in the Absence of the Viral E3 Protein.Journal of virology · 2018Article
- Structural and Functional Insight into Canarypox Virus CNP058 Mediated Regulation of Apoptosis.Viruses · 2017Article
- Review
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Authors and funding
11 authors at 6 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Viral infection is a stimulus for apoptosis, and in order to sustain viral replication many viruses are known to carry genes encoding apoptosis inhibitors. F1L, encoded by the orthopoxvirus modified vaccinia virus Ankara (MVA) has a Bcl-2-like structure. An MVA mutant lacking F1L (MVAΔF1L) induces apoptosis, indicating that MVA infection activates and F1L functions to inhibit the apoptotic pathway. In this study we investigated the events leading to apoptosis upon infection by MVAΔF1L. Apoptosis largely proceeded through the pro-apoptotic Bcl-2 family protein Bak with some contribution from Bax. Of the family of pro-apoptotic BH3-only proteins, only the loss of Noxa provided substantial protection, while the loss of Bim had a minor effect. In mice, MVA preferentially infected macrophages and DCs in vivo. In both cell types wt MVA induced apoptosis albeit more weakly than MVAΔF1L. The loss of Noxa had a significant protective effect in macrophages, DC and primary lymphocytes, and the combined loss of Bim and Noxa provided strong protection. Noxa protein was induced during infection, and the induction of Noxa protein and apoptosis induction required transcription factor IRF3 and type I interferon signalling. We further observed that helicases RIG-I and MDA5 and their signalling adapter MAVS contribute to Noxa induction and apoptosis in response to MVA infection. RNA isolated from MVA-infected cells induced Noxa expression and apoptosis when transfected in the absence of viral infection. We thus here describe a pathway leading from the detection of viral RNA during MVA infection by the cytosolic helicase-pathway, to the up-regulation of Noxa and apoptosis via IRF3 and type I IFN signalling.
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