tetano
Editor, Senior Moderator
AMB Express. 2016 Dec;6(1):16. doi: 10.1186/s13568-016-0187-y. Epub 2016 Feb 24.
[h=1]Inhibiting avian influenza virus shedding using a novel RNAi antiviral vector technology: proof of concept in an avian cell model.[/h] Linke LM[SUP]1,[/SUP][SUP]2[/SUP], Wilusz J[SUP]3[/SUP], Pabilonia KL[SUP]4,[/SUP][SUP]5[/SUP], Fruehauf J[SUP]6[/SUP], Magnuson R[SUP]7,[/SUP][SUP]8[/SUP], Olea-Popelka F[SUP]9[/SUP], Triantis J[SUP]10,[/SUP][SUP]11,[/SUP][SUP]12[/SUP], Landolt G[SUP]13[/SUP], Salman M[SUP]14,[/SUP][SUP]15[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] 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.
[h=4]KEYWORDS:[/h] Avian influenza; Bacterial vector; Influenza antiviral; Transkingdom RNAi; siRNA delivery
PMID: 26910902 [PubMed]
[h=1]Inhibiting avian influenza virus shedding using a novel RNAi antiviral vector technology: proof of concept in an avian cell model.[/h] Linke LM[SUP]1,[/SUP][SUP]2[/SUP], Wilusz J[SUP]3[/SUP], Pabilonia KL[SUP]4,[/SUP][SUP]5[/SUP], Fruehauf J[SUP]6[/SUP], Magnuson R[SUP]7,[/SUP][SUP]8[/SUP], Olea-Popelka F[SUP]9[/SUP], Triantis J[SUP]10,[/SUP][SUP]11,[/SUP][SUP]12[/SUP], Landolt G[SUP]13[/SUP], Salman M[SUP]14,[/SUP][SUP]15[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] 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.
[h=4]KEYWORDS:[/h] Avian influenza; Bacterial vector; Influenza antiviral; Transkingdom RNAi; siRNA delivery
PMID: 26910902 [PubMed]