Inoculation of newborn mice with non-coding regions of foot-and-mouth disease virus RNA can induce a rapid, solid and wide-range protection against viral infection

Antiviral Research In Press, Accepted Manuscript - Note to users doi:10.1016/j.antiviral.2011.10.005 | How to Cite or Link Using DOI   Permissions & Reprints Short communication Inoculation of newborn mice with non-coding regions of foot-and-mouth disease virus RNA can induce a rapid, solid and wide-range protection against viral infection Miguel Rodríguez-Pulidoa, b, Francisco Sobrinob, Belén Borregoc, Margarita Sáizb, ,  Purchase a Centre de Recerca en Sanitat Animal (CReSA), UAB-IRTA, Bellaterra, 08193 Barcelona, Spain b Centro de Biología Molecular Severo Ochoa (CSIC-UAM), Cantoblanco, 28049 Madrid, Spain c CISA-INIA, Valdeolmos, 28130 Madrid, Spain Received 20 June 2011; revised 3 October 2011; Accepted 5 October 2011. Available online 12 October 2011. Abstract We have recently described the ability of in vitro-transcribed RNAs, mimicking structural domains in the 5´ and 3´ non-coding regions (NCRs) of the foot-and-mouth disease virus (FMDV) genome, to trigger the innate immune response in porcine cultured cells and mice. In this work, the antiviral effect exerted in vivo by these small synthetic non-infectious RNA molecules was analyzed extensively. The susceptibility of transfected newborn Swiss mice to FMDV challenge was tested using a wide range of viral doses. The level of protection depended on the specific RNA inoculated and was dose-dependent. The RNA giving the best protection was the internal ribosome entry site (IRES), followed by the transcripts corresponding to the S fragment. The time course of resistance to FMDV of the RNA-transfected mice was studied. Our results show the efficacy of these RNAs to prevent viral infection as well as to contain ongoing FMDV infection in certain time intervals. Protection proved to be independent of the serotype of FMDV used for challenge. These results support the potential use of the FMDV NCR transcripts as both prophylactic and therapeutic molecules for new FMDV control strategies. Highlights ► FMDV NCRs have prophylactic and therapeutic activity against viral infection ► FMDV IRES induces heterotypic protection against virus challenge in suckling mice ► FMDV 5´ and 3´ NCR transcripts induce dose-dependent protection against FMDV Keywords: Foot-and-mouth disease; viral non-coding regions; RNA antiviral activity; anti-FMDV strategies; innate immunity