Inhibiting avian influenza virus shedding using a novel RNAi antiviral vector technology: proof of concept in an avian cell model
| Autor: | Joni Triantis, Francisco Olea-Popelka, Gabriele A. Landolt, Jeffrey Wilusz, Mo Salman, Johannes Fruehauf, Kristy L. Pabilonia, Lyndsey M. Linke, Roberta J. Magnuson |
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| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Small interfering RNA siRNA delivery Bacterial vector animal diseases Biophysics Avian influenza medicine.disease_cause Applied Microbiology and Biotechnology 03 medical and health sciences 0302 clinical medicine RNA interference medicine Vector (molecular biology) Transkingdom RNAi Gene Polymerase biology virus diseases Virology Influenza A virus subtype H5N1 In vitro Nucleoprotein 030104 developmental biology 030220 oncology & carcinogenesis Influenza antiviral biology.protein Original Article |
| Zdroj: | AMB Express |
| ISSN: | 2191-0855 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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