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  • Potent Inhibition of Hendra Virus Infection via RNA Interference and Poly I:C Immune Activation

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    Author(s)
    McCaskill, Jana L
    Marsh, Glenn A
    Monaghan, Paul
    Wang, Lin-Fa
    Doran, Timothy
    McMillan, Nigel AJ
    Griffith University Author(s)
    McMillan, Nigel
    Year published
    2013
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    Abstract
    Hendra virus (HeV) is a highly pathogenic zoonotic paramyxovirus that causes fatal disease in a wide range of species, including humans. HeV was first described in Australia in 1994, and has continued to re-emerge with increasing frequency. HeV is of significant concern to human health due to its high mortality rate, increasing emergence, absence of vaccines and limited post exposure therapies. Here we investigate the use of RNA interference (RNAi) based therapeutics targeting HeV in conjunction with the TLR3 agonist Poly I:C and show that they are potent inhibitors of HeV infection in vitro. We found that short interfering ...
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    Hendra virus (HeV) is a highly pathogenic zoonotic paramyxovirus that causes fatal disease in a wide range of species, including humans. HeV was first described in Australia in 1994, and has continued to re-emerge with increasing frequency. HeV is of significant concern to human health due to its high mortality rate, increasing emergence, absence of vaccines and limited post exposure therapies. Here we investigate the use of RNA interference (RNAi) based therapeutics targeting HeV in conjunction with the TLR3 agonist Poly I:C and show that they are potent inhibitors of HeV infection in vitro. We found that short interfering RNAs (siRNAs) targeting the abundantly expressed N, P and M genes of HeV caused over 95% reduction of HeV virus titre, protein and mRNA. Furthermore, we found that the combination of HeV targeting siRNA and Poly I:C had an additive effect in suppressing HeV infection. Our results demonstrate for the first time that RNAi and type I interferon stimulation are effective inhibitors of HeV replication in vitro and may provide an effective therapy for this highly lethal, zoonotic pathogen.
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    Journal Title
    PLoS One
    Volume
    8
    Issue
    5
    DOI
    https://doi.org/10.1371/journal.pone.0064360
    Copyright Statement
    © 2013 McCaskill et al. This is an Open Access article distributed under the terms of the Creative Commons Attribution License CCAL. (http://www.plos.org/journals/license.html)
    Subject
    Gene and Molecular Therapy
    Publication URI
    http://hdl.handle.net/10072/54750
    Collection
    • Journal articles

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