The interferon stimulated gene viperin, restricts Shigella. flexneri in vitro
Autor: | Ebony A. Monson, Keaton M. Crosse, Elizabeth Ngoc Hoa Tran, Renato Morona, Monique Smith, Michael R. Beard, Min Yan Teh, Alistair J. Standish, Karla J. Helbig |
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Jazyk: | angličtina |
Rok vydání: | 2019 |
Předmět: |
Transcriptional Activation
0301 basic medicine Oxidoreductases Acting on CH-CH Group Donors lcsh:Medicine Biology Microbiology Article Cell Line Shigella flexneri 03 medical and health sciences Interferon medicine Humans lcsh:Science Innate immunity Regulation of gene expression Multidisciplinary 030102 biochemistry & molecular biology Intracellular parasite Interferon-stimulated gene lcsh:R Proteins Bacteriology Antimicrobial responses biology.organism_classification Cholesterol 030104 developmental biology Gene Expression Regulation Viperin Ectopic expression lcsh:Q Interferons Intracellular medicine.drug |
Zdroj: | Scientific Reports, Vol 9, Iss 1, Pp 1-12 (2019) Scientific Reports |
ISSN: | 2045-2322 |
Popis: | The role of interferon and interferon stimulated genes (ISG) in limiting bacterial infection is controversial, and the role of individual ISGs in the control of the bacterial life-cycle is limited. Viperin, is a broad acting anti-viral ISGs, which restricts multiple viral pathogens with diverse mechanisms. Viperin is upregulated early in some bacterial infections, and using the intracellular bacterial pathogen, S. flexneri, we have shown for the first time that viperin inhibits the intracellular bacterial life cycle. S. flexneri replication in cultured cells induced a predominantly type I interferon response, with an early increase in viperin expression. Ectopic expression of viperin limited S. flexneri cellular numbers by as much as 80% at 5hrs post invasion, with similar results also obtained for the intracellular pathogen, Listeria monocytogenes. Analysis of viperins functional domains required for anti-bacterial activity revealed the importance of both viperin’s N-terminal, and its radical SAM enzymatic function. Live imaging of S. flexneri revealed impeded entry into viperin expressing cells, which corresponded to a loss of cellular cholesterol. This data further defines viperin’s multi-functional role, to include the ability to limit intracellular bacteria; and highlights the role of ISGs and the type I IFN response in the control of bacterial pathogens. |
Databáze: | OpenAIRE |
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