ArticleJournal of immunology (Baltimore, Md. : 1950)2014
Simian virus 40 large T antigen induces IFN-stimulated genes through ATR kinase.
Article in Journal of immunology (Baltimore, Md. : 1950), 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 36 citations in OpenAlex.
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- Epigenetic regulation of IFITM1 expression in lipopolysaccharide-stimulated human mesenchymal stromal cells.Stem cell research & therapy · 2020Article
- Checkpoint inhibitor blockade and epigenetic reprogrammability in CD8Therapeutic advances in vaccines and immunotherapy · 2020Review
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- ATR-mediated proteome remodeling is a major determinant of homologous recombination capacity in cancer cells.Nucleic acids research · 2018Article
- Differential Responses by Human Respiratory Epithelial Cell Lines to Respiratory Syncytial Virus Reflect Distinct Patterns of Infection Control.Journal of virology · 2018Article
- Topoisomerase 1 Inhibition Promotes Cyclic GMP-AMP Synthase-Dependent Antiviral Responses.mBio · 2017Article
- The Importance of Physiologically Relevant Cell Lines for Studying Virus-Host Interactions.Viruses · 2016Review
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Polyomaviruses encode a large T Ag (LT), a multifunctional protein essential for the regulation of both viral and host cell gene expression and productive viral infection. Previously, we have shown that stable expression of LT protein results in upregulation of genes involved in the IFN induction and signaling pathway. In this study, we focus on the cellular signaling mechanism that leads to the induction of IFN responses by LT. Our results show that ectopic expression of SV40 LT results in the induction of IFN-stimulated genes (ISGs) in human fibroblasts and confers an antiviral state. We describe a LT-initiated DNA damage response (DDR) that activates IFN regulatory factor 1, causing IFN-β production and consequent ISG expression in human cells. This IFN-β and ISG induction is dependent on ataxia-telangiectasia mutated and Rad3-related (ATR) kinase, but independent of ATM. ATR kinase inhibition using a selective kinase inhibitor (ETP-46464) caused a decrease in IFN regulatory factor 1 stabilization and ISG expression. Furthermore, expression of a mutant LT that does not induce DDR also does not induce IFN-β and ISGs. These results show that, in the absence of viral infection, LT-initiated activation of ATR-dependent DDR is sufficient for the induction of an IFN-β-mediated innate immune response in human cells. Thus, we have uncovered a novel and critical role for ATR as a mediator of antiviral responses utilizing LT.
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