Potent inhibition of Hendra virus infection via RNA interference and poly I:C immune activation

PLoS One. 2013 May 14;8(5):e64360. doi: 10.1371/journal.pone.0064360. Print 2013.

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 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • HeLa Cells
  • Hendra Virus / immunology*
  • Hendra Virus / physiology
  • Henipavirus Infections / genetics*
  • Henipavirus Infections / immunology*
  • Humans
  • Poly I-C / immunology*
  • RNA Interference*
  • Toll-Like Receptor 3 / deficiency
  • Toll-Like Receptor 3 / genetics
  • Viral Load / genetics
  • Viral Load / immunology

Substances

  • TLR3 protein, human
  • Toll-Like Receptor 3
  • Poly I-C

Grants and funding

This work was supported by program grant APP 1040904 and 631402 from the National Health and Medical Research Council (NHMRC) of Australia. JM was supported by UQ Diamantina Institute, Australian Postgraduate Award and the Australian Federation of Graduate Women Fellowship. The authors acknowledge the support of the Australian Microscopy and Microanalysis Research Facility. The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.