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The interferon stimulated gene viperin, restricts Shigella. flexneri in vitro
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 mech...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6821890/ https://www.ncbi.nlm.nih.gov/pubmed/31666594 http://dx.doi.org/10.1038/s41598-019-52130-8 |
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author | Helbig, K. J. Teh, M. Y. Crosse, K. M. Monson, E. A. Smith, M. Tran, E. N. Standish, A. J. Morona, R. Beard, M. R. |
author_facet | Helbig, K. J. Teh, M. Y. Crosse, K. M. Monson, E. A. Smith, M. Tran, E. N. Standish, A. J. Morona, R. Beard, M. R. |
author_sort | Helbig, K. J. |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-6821890 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-68218902019-11-05 The interferon stimulated gene viperin, restricts Shigella. flexneri in vitro Helbig, K. J. Teh, M. Y. Crosse, K. M. Monson, E. A. Smith, M. Tran, E. N. Standish, A. J. Morona, R. Beard, M. R. Sci Rep Article 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. Nature Publishing Group UK 2019-10-30 /pmc/articles/PMC6821890/ /pubmed/31666594 http://dx.doi.org/10.1038/s41598-019-52130-8 Text en © The Author(s) 2019 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Helbig, K. J. Teh, M. Y. Crosse, K. M. Monson, E. A. Smith, M. Tran, E. N. Standish, A. J. Morona, R. Beard, M. R. The interferon stimulated gene viperin, restricts Shigella. flexneri in vitro |
title | The interferon stimulated gene viperin, restricts Shigella. flexneri in vitro |
title_full | The interferon stimulated gene viperin, restricts Shigella. flexneri in vitro |
title_fullStr | The interferon stimulated gene viperin, restricts Shigella. flexneri in vitro |
title_full_unstemmed | The interferon stimulated gene viperin, restricts Shigella. flexneri in vitro |
title_short | The interferon stimulated gene viperin, restricts Shigella. flexneri in vitro |
title_sort | interferon stimulated gene viperin, restricts shigella. flexneri in vitro |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6821890/ https://www.ncbi.nlm.nih.gov/pubmed/31666594 http://dx.doi.org/10.1038/s41598-019-52130-8 |
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