Scientific reports, 2019-06, Vol.9 (1), p.9413-10, Article 9413
2019
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- Autor(en) / Beteiligte
- Titel
- Manassantin B shows antiviral activity against coxsackievirus B3 infection by activation of the STING/TBK-1/IRF3 signalling pathway
- Ist Teil von
- Scientific reports, 2019-06, Vol.9 (1), p.9413-10, Article 9413
- Ort / Verlag
- England: Nature Publishing Group
- Erscheinungsjahr
- 2019
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- Coxsackievirus B3 (CVB3) is an important human pathogen associated with the development of acute pancreatitis, myocarditis, and type 1 diabetes. Currently, no vaccines or antiviral therapeutics are approved for the prevention and treatment of CVB3 infection. We found that Saururus chinensis Baill extract showed critical antiviral activity against CVB3 infection in vitro. Further, manassantin B inhibited replication of CVB3 and suppressed CVB3 VP1 protein expression in vitro. Additionally, oral administration of manassantin B in mice attenuated CVB3 infection-associated symptoms by reducing systemic production of inflammatory cytokines and chemokines including TNF-α, IL-6, IFN-γ, CCL2, and CXCL-1. We found that the antiviral activity of manassantin B is associated with increased levels of mitochondrial ROS (mROS). Inhibition of mROS generation attenuated the antiviral activity of manassantin B in vitro. Interestingly, we found that manassantin B also induced cytosolic release of mitochondrial DNA based on cytochrome C oxidase DNA levels. We further confirmed that STING and IRF-3 expression and STING and TBK-1 phosphorylation were increased by manassantin B treatment in CVB3-infected cells. Collectively, these results suggest that manassantin B exerts antiviral activity against CVB3 through activation of the STING/TKB-1/IRF3 antiviral pathway and increased production of mROS.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 2045-2322eISSN: 2045-2322DOI: 10.1038/s41598-019-45868-8Titel-ID: cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_6599049
- Format
- –
- Schlagworte
- Animals, Antiviral activity, Antiviral Agents - pharmacology, Beta cells, Chemokines, Chlorocebus aethiops, Coxsackievirus Infections - drug therapy, Coxsackievirus Infections - metabolism, Coxsackievirus Infections - virology, Coxsackieviruses, Cytochrome-c oxidase, Cytokines - metabolism, Diabetes mellitus, Diabetes mellitus (insulin dependent), Electron Transport Chain Complex Proteins - antagonists & inhibitors, Enterovirus B, Human - drug effects, Female, Furans - pharmacology, Heart diseases, Humans, Infections, Inflammation, Inflammation Mediators - metabolism, Interferon regulatory factor 3, Interferon Regulatory Factor-3 - metabolism, Interleukin 6, Membrane Proteins - metabolism, Mice, Mitochondria - metabolism, Mitochondrial DNA, Monocyte chemoattractant protein 1, Myocarditis, Oral administration, Pancreatitis, Phosphorylation, Plant Extracts - pharmacology, Protein-Serine-Threonine Kinases - metabolism, Reactive oxygen species, Signal transduction, Signal Transduction - drug effects, Tumor necrosis factor-α, Vero Cells, Virus Replication - drug effects, VP1 protein, γ-Interferon