Protection against West Nile virus infection in mice after inoculation with type I interferon-inducing RNA transcripts

PLoS One. 2012;7(11):e49494. doi: 10.1371/journal.pone.0049494. Epub 2012 Nov 14.

Abstract

West Nile virus (WNV) is a neurovirulent single stranded RNA mosquito-borne flavivirus, whose main natural hosts are birds, but it also infects humans and horses. Nowadays, no human vaccine is commercially available and clinical treatment is only supportive. Recently, it has been shown that RNA transcripts, mimicking structural domains in the non-coding regions (NCRs) of the foot-and mouth disease virus (FMDV) induce a potent IFN response and antiviral activity in transfected cultured cells, and also reduced mice susceptibility to FMDV. By using different transcripts combinations, administration schedules, and infecting routes and doses, we have demonstrated that these FMDV RNA transcripts protect suckling and adult mice against lethal challenge with WNV. The protective activity induced by the transcripts was systemic and dependent on the infection route and dose. These results confirm the antiviral potential of these synthetic RNAs for fighting viruses of different families relevant for human and animal health.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Gene Expression Regulation, Viral
  • Immunity, Innate
  • Interferon Type I / blood*
  • Interferon Type I / immunology
  • Mice
  • RNA, Untranslated / genetics
  • RNA, Viral / genetics*
  • West Nile Fever / immunology*
  • West Nile Fever / mortality
  • West Nile Fever / prevention & control*
  • West Nile virus / genetics*
  • West Nile virus / immunology*

Substances

  • Interferon Type I
  • RNA, Untranslated
  • RNA, Viral

Grants and funding

Work was supported by grants Recursos y Tecnologías Agrarias (RTA2011-00036) from Instituto Nacional de Investigación Agraria y Alimentaria, Biomedicina (BIO2011-24351) and Agricultura (AGL2011-24509) from the Spanish Ministerio de Ciencia e Innovación (MICINN), an Institutional grant from Fundación Ramón Areces, and by the Network of Animal Disease Infectiology and Research-European Union NADIR-EU-228394. MRP is the recipient of a “Juan de la Cierva” fellowship from MICINN and MAMA of a Junta de Ampliación de Estudios (JAE)-Doctoral fellowship from Spanish Research Council (CSIC). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.