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Inhibiting avian influenza virus shedding using a novel RNAi antiviral vector technology: proof of concept in an avian cell model
Influenza A viruses pose significant health and economic threats to humans and animals. Outbreaks of avian influenza virus (AIV) are a liability to the poultry industry and increase the risk for transmission to humans. There are limitations to using the AIV vaccine in poultry, creating barriers to c...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Springer Berlin Heidelberg
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4766140/ https://www.ncbi.nlm.nih.gov/pubmed/26910902 http://dx.doi.org/10.1186/s13568-016-0187-y |
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author | Linke, Lyndsey M. Wilusz, Jeffrey Pabilonia, Kristy L. Fruehauf, Johannes Magnuson, Roberta Olea-Popelka, Francisco Triantis, Joni Landolt, Gabriele Salman, Mo |
author_facet | Linke, Lyndsey M. Wilusz, Jeffrey Pabilonia, Kristy L. Fruehauf, Johannes Magnuson, Roberta Olea-Popelka, Francisco Triantis, Joni Landolt, Gabriele Salman, Mo |
author_sort | Linke, Lyndsey M. |
collection | PubMed |
description | Influenza A viruses pose significant health and economic threats to humans and animals. Outbreaks of avian influenza virus (AIV) are a liability to the poultry industry and increase the risk for transmission to humans. There are limitations to using the AIV vaccine in poultry, creating barriers to controlling outbreaks and a need for alternative effective control measures. Application of RNA interference (RNAi) techniques hold potential; however, the delivery of RNAi-mediating agents is a well-known obstacle to harnessing its clinical application. We introduce a novel antiviral approach using bacterial vectors that target avian mucosal epithelial cells and deliver (small interfering RNA) siRNAs against two AIV genes, nucleoprotein (NP) and polymerase acidic protein (PA). Using a red fluorescent reporter, we first demonstrated vector delivery and intracellular expression in avian epithelial cells. Subsequently, we demonstrated significant reductions in AIV shedding when applying these anti-AIV vectors prophylactically. These antiviral vectors provided up to a 10,000-fold reduction in viral titers shed, demonstrating in vitro proof-of-concept for using these novel anti-AIV vectors to inhibit AIV shedding. Our results indicate this siRNA vector technology could represent a scalable and clinically applicable antiviral technology for avian and human influenza and a prototype for RNAi-based vectors against other viruses. |
format | Online Article Text |
id | pubmed-4766140 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Springer Berlin Heidelberg |
record_format | MEDLINE/PubMed |
spelling | pubmed-47661402016-03-29 Inhibiting avian influenza virus shedding using a novel RNAi antiviral vector technology: proof of concept in an avian cell model Linke, Lyndsey M. Wilusz, Jeffrey Pabilonia, Kristy L. Fruehauf, Johannes Magnuson, Roberta Olea-Popelka, Francisco Triantis, Joni Landolt, Gabriele Salman, Mo AMB Express Original Article Influenza A viruses pose significant health and economic threats to humans and animals. Outbreaks of avian influenza virus (AIV) are a liability to the poultry industry and increase the risk for transmission to humans. There are limitations to using the AIV vaccine in poultry, creating barriers to controlling outbreaks and a need for alternative effective control measures. Application of RNA interference (RNAi) techniques hold potential; however, the delivery of RNAi-mediating agents is a well-known obstacle to harnessing its clinical application. We introduce a novel antiviral approach using bacterial vectors that target avian mucosal epithelial cells and deliver (small interfering RNA) siRNAs against two AIV genes, nucleoprotein (NP) and polymerase acidic protein (PA). Using a red fluorescent reporter, we first demonstrated vector delivery and intracellular expression in avian epithelial cells. Subsequently, we demonstrated significant reductions in AIV shedding when applying these anti-AIV vectors prophylactically. These antiviral vectors provided up to a 10,000-fold reduction in viral titers shed, demonstrating in vitro proof-of-concept for using these novel anti-AIV vectors to inhibit AIV shedding. Our results indicate this siRNA vector technology could represent a scalable and clinically applicable antiviral technology for avian and human influenza and a prototype for RNAi-based vectors against other viruses. Springer Berlin Heidelberg 2016-02-24 /pmc/articles/PMC4766140/ /pubmed/26910902 http://dx.doi.org/10.1186/s13568-016-0187-y Text en © Linke et al. 2016 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided 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. |
spellingShingle | Original Article Linke, Lyndsey M. Wilusz, Jeffrey Pabilonia, Kristy L. Fruehauf, Johannes Magnuson, Roberta Olea-Popelka, Francisco Triantis, Joni Landolt, Gabriele Salman, Mo Inhibiting avian influenza virus shedding using a novel RNAi antiviral vector technology: proof of concept in an avian cell model |
title | Inhibiting avian influenza virus shedding using a novel RNAi antiviral vector technology: proof of concept in an avian cell model |
title_full | Inhibiting avian influenza virus shedding using a novel RNAi antiviral vector technology: proof of concept in an avian cell model |
title_fullStr | Inhibiting avian influenza virus shedding using a novel RNAi antiviral vector technology: proof of concept in an avian cell model |
title_full_unstemmed | Inhibiting avian influenza virus shedding using a novel RNAi antiviral vector technology: proof of concept in an avian cell model |
title_short | Inhibiting avian influenza virus shedding using a novel RNAi antiviral vector technology: proof of concept in an avian cell model |
title_sort | inhibiting avian influenza virus shedding using a novel rnai antiviral vector technology: proof of concept in an avian cell model |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4766140/ https://www.ncbi.nlm.nih.gov/pubmed/26910902 http://dx.doi.org/10.1186/s13568-016-0187-y |
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