ArticleJournal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research2018
Constitutively Active MDA5 Proteins Are Inhibited by Paramyxovirus V Proteins.
Article in Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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Who cites it
6 citing papers in PubMed, 10 citations in OpenAlex.
- Emerging roles of the Protein Phosphatase 1 (PP1) in the context of viral infections.Cell communication and signaling : CCS · 2024Review
- Molecular biology of canine parainfluenza virus V protein and its potential applications in tumor immunotherapy.Frontiers in microbiology · 2023Review
- MDA5 disease variant M854K prevents ATP-dependent structural discrimination of viral and cellular RNA.Nature communications · 2021Article
- Innate Inhibiting Proteins Enhance Expression and Immunogenicity of Self-Amplifying RNA.Molecular therapy : the journal of the American Society of Gene Therapy · 2021Article
- MDA5 cleavage by the Leader protease of foot-and-mouth disease virus reveals its pleiotropic effect against the host antiviral response.Cell death & disease · 2020Article
- Review
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Excessive interferon (IFN) production and signaling can lead to immunological and developmental defects giving rise to autoimmune diseases referred to collectively as "type I interferonopathies." A subset of these diseases is caused by monogenic mutations affecting proteins involved in nucleic acid sensing, homeostasis, and metabolism. Interferonopathic mutations in the cytosolic antiviral sensor MDA5 render it constitutively hyperactive, resulting in chronic IFN production and IFN-stimulated gene expression. Few therapeutic options are available for patients with interferonopathic diseases, but a large number of IFN evasion and antagonism strategies have evolved in viral pathogens that can counteract IFN production and signaling to enhance virus replication. To test the hypothesis that these natural IFN suppressors could be used to subdue the activity of interferonopathic signaling proteins, hyperactive MDA5 variants were assessed for susceptibility to a family of viral MDA5 inhibitors. In this study, Paramyxovirus V proteins were tested for their ability to counteract constitutively active MDA5 proteins. Results indicate that the V proteins are able to bind to and disrupt the signaling activity of these MDA5 proteins, irrespective of their specific mutations, reducing IFN production and IFN-stimulated gene expression to effectively suppress the hyperactive antiviral response.
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Registered trials
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