title: Protection against Rift Valley fever virus infection in mice upon administration of interferon-inducing RNA transcripts from the FMDV genome.
abstract: In this work we have addressed the effect of synthetic, non-infectious, RNA transcripts, mimicking structural domains of the non-coding regions (NCRs) of the foot-and-mouth disease virus (FMDV) genome on the infection of mice with Rift Valley fever virus (RVFV). Groups of 5 mice were inoculated intraperitoneally (i.p.) with 200 μg of synthetic RNA resembling the 5'-terminal S region, the internal ribosome entry site (IRES) or the 3'-NCR of the FMDV genome. RNA inoculation was performed 24h before (-24 h), 24 h after (+24 h) or simultaneously to the challenge with a lethal dose of RVFV. Administration of the IRES RNA afforded higher survival rates than administration of S or 3'NCR transcripts either at -24h or +24h after challenge. In contrast, when RNA inoculation and viral challenge were performed simultaneously, all mice survived in both IRES- and 3'NCR-inoculated groups, with an 80% survival in mice receiving the S RNA. Among survivors, a complete correlation between significant anti-RVFV circulating antibody titers and resistance to a second lethal challenge with the virus was observed, supporting a limited viral replication in the RNA-inoculated animals upon the first challenge. All three RNA transcripts were able to induce the production of systemic antiviral and pro-inflammatory cytokines. These data show that triggering of intracellular pathogen sensing pathways constitutes a promising approach towards development of novel RVF preventive or therapeutic strategies.
authors: Centro de Investigación en Sanidad Animal - INIA, Valdeolmos 28130, Madrid, Spain.
authors: Gema
authors: G
authors: Lorenzo
authors: Centro de Biología Molecular "Severo Ochoa" (CSIC-UAM), Cantoblanco 28049, Madrid, Spain.
authors: Miguel
authors: M
authors: Rodríguez-Pulido
authors: Centro de Investigación en Sanidad Animal - INIA, Valdeolmos 28130, Madrid, Spain.
authors: Elena
authors: E
authors: López-Gil
authors: Centro de Biología Molecular "Severo Ochoa" (CSIC-UAM), Cantoblanco 28049, Madrid, Spain.
authors: Francisco
authors: F
authors: Sobrino
authors: Centro de Investigación en Sanidad Animal - INIA, Valdeolmos 28130, Madrid, Spain.
authors: Belén
authors: B
authors: Borrego
authors: Centro de Biología Molecular "Severo Ochoa" (CSIC-UAM), Cantoblanco 28049, Madrid, Spain.
authors: Margarita
authors: M
authors: Sáiz
authors: Centro de Investigación en Sanidad Animal - INIA, Valdeolmos 28130, Madrid, Spain. Electronic address: brun@inia.es.
authors: Alejandro
authors: A
authors: Brun
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000276:immunology; D056738:Cross Protection; D029544:Foot-and-Mouth Disease Virus / Q000235:genetics* / Q000276:immunology; D016679:Genome, Viral; D006801:Humans; D007372:Interferons / Q000008:administration & dosage*; D051379:Mice; D008807:Mice, Inbred BALB C; D012367:RNA, Viral / Q000008:administration & dosage / Q000138:chemical synthesis / Q000235:genetics / Q000276:immunology*; D012295:Rift Valley Fever / Q000276:immunology / Q000517:prevention & control* / Q000821:virology; D012296:Rift Valley fever virus / Q000276:immunology* / Q000502:physiology; D014611:Vaccination; D014765:Viral Vaccines / Q000008:administration & dosage / Q000138:chemical synthesis / Q000235:genetics / Q000276:immunology*; D014779:Virus Replication
chemical_list: D000914:Antibodies, Viral; D012367:RNA, Viral; D014765:Viral Vaccines; D007372:Interferons
keywords: Foot and mouth disease virus; Innate immunity; Non coding RNA regions; Rift Valley fever