{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,15]],"date-time":"2026-06-15T23:42:45Z","timestamp":1781566965155,"version":"3.54.5"},"reference-count":45,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2015,7,17]],"date-time":"2015-07-17T00:00:00Z","timestamp":1437091200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>The innate immune system is the first line of defense against viral infections. Exploiting innate responses for antiviral, therapeutic and vaccine adjuvation strategies is being extensively explored. We have previously described, the ability of small in vitro RNA transcripts, mimicking the sequence and structure of different domains in the non-coding regions of the foot-and-mouth disease virus (FMDV) genome (ncRNAs), to trigger a potent and rapid innate immune response. These synthetic non-infectious molecules have proved to have a broad-range antiviral activity and to enhance the immunogenicity of an FMD inactivated vaccine in mice. Here, we have studied the involvement of pattern-recognition receptors (PRRs) in the ncRNA-induced innate response and analyzed the antiviral and cytokine profiles elicited in swine cultured cells, as well as peripheral blood mononuclear cells (PBMCs).<\/jats:p>","DOI":"10.3390\/v7072807","type":"journal-article","created":{"date-parts":[[2015,7,17]],"date-time":"2015-07-17T11:18:48Z","timestamp":1437131928000},"page":"3954-3973","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Synthetic RNAs Mimicking Structural Domains in the Foot-and-Mouth Disease Virus Genome Elicit a Broad Innate Immune Response in Porcine Cells Triggered by RIG-I and TLR Activation"],"prefix":"10.3390","volume":"7","author":[{"given":"Bel\u00e9n","family":"Borrego","sequence":"first","affiliation":[{"name":"Centro de Investigaci\u00f3n en Sanidad Animal, CISA-INIA, Valdeolmos, Madrid 28130, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2101-8974","authenticated-orcid":false,"given":"Miguel","family":"Rodr\u00edguez-Pulido","sequence":"additional","affiliation":[{"name":"Centro de Biolog\u00eda Molecular Severo Ochoa (CISC-UAM), Cantoblanco, Madrid 28049, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Concepci\u00f3n","family":"Revilla","sequence":"additional","affiliation":[{"name":"Dpto. de Biotecnolog\u00eda, Instituto Nacional de Investigaci\u00f3n y Tecnolog\u00eda Agraria y Alimentaria (INIA), Ctra de la Coru\u00f1a Km 7.5, Madrid 28040, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bel\u00e9n","family":"\u00c1lvarez","sequence":"additional","affiliation":[{"name":"Dpto. de Biotecnolog\u00eda, Instituto Nacional de Investigaci\u00f3n y Tecnolog\u00eda Agraria y Alimentaria (INIA), Ctra de la Coru\u00f1a Km 7.5, Madrid 28040, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francisco","family":"Sobrino","sequence":"additional","affiliation":[{"name":"Centro de Biolog\u00eda Molecular Severo Ochoa (CISC-UAM), Cantoblanco, Madrid 28049, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Javier","family":"Dom\u00ednguez","sequence":"additional","affiliation":[{"name":"Dpto. de Biotecnolog\u00eda, Instituto Nacional de Investigaci\u00f3n y Tecnolog\u00eda Agraria y Alimentaria (INIA), Ctra de la Coru\u00f1a Km 7.5, Madrid 28040, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margarita","family":"S\u00e1iz","sequence":"additional","affiliation":[{"name":"Centro de Biolog\u00eda Molecular Severo Ochoa (CISC-UAM), Cantoblanco, Madrid 28049, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2015,7,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1146\/annurev-immunol-031210-101340","article-title":"Nucleic acid recognition by the innate immune system","volume":"29","author":"Barbalat","year":"2011","journal-title":"Annu. Rev. Immunol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"4999","DOI":"10.3390\/v6124999","article-title":"Interferon induction by rna viruses and antagonism by viral pathogens","volume":"6","author":"Nan","year":"2014","journal-title":"Viruses"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1246","DOI":"10.1016\/j.jmb.2013.11.024","article-title":"Toll-like receptors in antiviral innate immunity","volume":"426","author":"Lester","year":"2014","journal-title":"J. Mol. Biol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1016\/B978-0-12-410524-9.00004-9","article-title":"Intracellular pathogen detection by RIG-I-like receptors","volume":"117","author":"Dixit","year":"2013","journal-title":"Adv. Immunol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1322","DOI":"10.1016\/j.imbio.2013.06.007","article-title":"Master sensors of pathogenic RNA\u2014RIG-I like receptors","volume":"218","author":"Schlee","year":"2013","journal-title":"Immunobiology"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"855","DOI":"10.1016\/j.immuni.2013.05.007","article-title":"Cytosolic sensing of viruses","volume":"38","author":"Goubau","year":"2013","journal-title":"Immunity"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"386","DOI":"10.1111\/cmi.12061","article-title":"Structural basis of innate immune recognition of viral RNA","volume":"15","author":"Berke","year":"2013","journal-title":"Cell. Microbiol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"546","DOI":"10.1038\/nri3713","article-title":"Assembly and localization of toll-like receptor signalling complexes","volume":"14","author":"Gay","year":"2014","journal-title":"Nat. Rev. Immunol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"5598","DOI":"10.1073\/pnas.0400937101","article-title":"Recognition of single-stranded rna viruses by toll-like receptor 7","volume":"101","author":"Lund","year":"2004","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1586\/erv.11.189","article-title":"Pattern recognition receptors: Sentinels in innate immunity and targets of new vaccine adjuvants","volume":"11","author":"Olive","year":"2012","journal-title":"Expert Rev. Vaccines"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1016\/j.ejcb.2011.01.015","article-title":"Sensing of viral nucleic acids by RIG-I: From translocation to translation","volume":"91","author":"Schmidt","year":"2012","journal-title":"Eur. J. Cell Biol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"6492","DOI":"10.1128\/JVI.00599-11","article-title":"RNA structural domains in non-coding regions of foot-and-mouth disease virus genome trigger innate immunity in porcine cells and mice","volume":"85","author":"Borrego","year":"2011","journal-title":"J. Virol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"500","DOI":"10.1016\/j.antiviral.2011.10.005","article-title":"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","volume":"92","author":"Sobrino","year":"2011","journal-title":"Antivir. Res."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"e49494","DOI":"10.1371\/journal.pone.0049494","article-title":"Protection against west nile virus infection in mice after inoculation with type I interferon-inducing rna transcripts","volume":"7","author":"Blazquez","year":"2012","journal-title":"PLoS ONE"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1016\/j.antiviral.2014.06.010","article-title":"Protection against rift valley fever virus infection in mice upon administration of interferon-inducing rna transcripts from the FMDV genome","volume":"109","author":"Lorenzo","year":"2014","journal-title":"Antivir. Res."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"3013","DOI":"10.1099\/vir.0.82059-0","article-title":"The 3\u2032 end of the foot-and-mouth disease virus genome establishes two distinct long-range RNA-RNA interactions with the 5\u2032 end region","volume":"87","author":"Serrano","year":"2006","journal-title":"J. Gen. Virol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"5079","DOI":"10.1093\/nar\/29.24.5079","article-title":"Conserved rna secondary structures in picornaviridae genomes","volume":"29","author":"Witwer","year":"2001","journal-title":"Nucleic Acids Res."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1016\/j.virusres.2015.01.012","article-title":"Picornavirus ires elements: Rna structure and host protein interactions","volume":"206","author":"Lozano","year":"2015","journal-title":"Virus Res."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1016\/0168-1702(92)90151-X","article-title":"Modifications of the 5\u2032 untranslated region of foot-and-mouth disease virus after prolonged persistence in cell culture","volume":"26","author":"Escarmis","year":"1992","journal-title":"Virus Res."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"4375","DOI":"10.1016\/j.vaccine.2013.07.008","article-title":"Delivery of synthetic RNA can enhance the immunogenicity of vaccines against foot-and-mouth disease virus (FMDV) in mice","volume":"31","author":"Borrego","year":"2013","journal-title":"Vaccine"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1016\/0165-2427(90)90133-D","article-title":"Inhibitory effect of african swine fever virus on lectin-dependent swine lymphocyte proliferation","volume":"26","author":"Gonzalez","year":"1990","journal-title":"Vet. Immunol. Immunopathol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"20252","DOI":"10.1074\/jbc.M109.089912","article-title":"Negative role of RIG-I serine 8 phosphorylation in the regulation of interferon-beta production","volume":"285","author":"Gack","year":"2010","journal-title":"J. Biol. Chem."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"514","DOI":"10.1128\/JVI.01265-06","article-title":"Inhibition of retinoic acid-inducible gene i-mediated induction of \u03b2 interferon by the NS1 protein of influenza a virus","volume":"81","author":"Mibayashi","year":"2007","journal-title":"J. Virol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"16303","DOI":"10.1073\/pnas.1005077107","article-title":"Preference of RIG-I for short viral rna molecules in infected cells revealed by next-generation sequencing","volume":"107","author":"Baum","year":"2010","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1374","DOI":"10.1017\/S1355838299991240","article-title":"Long-range RNA interactions between structural domains of the aphthovirus internal ribosome entry site (IRES)","volume":"5","author":"Ramos","year":"1999","journal-title":"RNA"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1016\/j.virol.2004.01.027","article-title":"Immunogenicity and T cell recognition in swine of foot-and-mouth disease virus polymerase 3D","volume":"322","author":"Blanco","year":"2004","journal-title":"Virology"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"2077","DOI":"10.1007\/s00705-003-0182-x","article-title":"Expression at mRNA level of cytokines and A238l gene in porcine blood-derived macrophages infected in vitro with african swine fever virus (ASFV) isolates of different virulence","volume":"148","author":"Gil","year":"2003","journal-title":"Arch. Virol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1111\/j.1365-2567.2004.01856.x","article-title":"Type-A CpG oligonucleotides activate exclusively porcine natural interferon-producing cells to secrete interferon-\u03b1, tumour necrosis factor-\u03b1 and interleukin-12","volume":"112","author":"Balmelli","year":"2004","journal-title":"Immunology"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"372","DOI":"10.1006\/excr.1999.4426","article-title":"Distribution and characteristics of betaii tubulin-enriched microtubules in interphase cells","volume":"248","author":"Parrales","year":"1999","journal-title":"Exp. Cell Res."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"601","DOI":"10.1016\/j.it.2004.08.010","article-title":"Ifn-inducible gtpases and immunity to intracellular pathogens","volume":"25","author":"MacMicking","year":"2004","journal-title":"Trends Immunol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1146\/annurev-immunol-031210-101345","article-title":"Plasmacytoid dendritic cells: Recent progress and open questions","volume":"29","author":"Reizis","year":"2011","journal-title":"Annu. Rev. Immunol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1615\/CritRevImmunol.v28.i1.40","article-title":"The role of plasmacytoid dendritic cell-derived ifn alpha in antiviral immunity","volume":"28","author":"Szabo","year":"2008","journal-title":"Crit. Rev. Immunol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1016\/j.dci.2008.05.005","article-title":"The porcine dendritic cell family","volume":"33","author":"Summerfield","year":"2009","journal-title":"Dev. Comp. Immunol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"807","DOI":"10.1002\/eji.201343806","article-title":"Self-priming determines high type I IFN production by plasmacytoid dendritic cells","volume":"44","author":"Kim","year":"2014","journal-title":"Eur. J. Immunol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1999","DOI":"10.1084\/jem.20060401","article-title":"Properties regulating the nature of the plasmacytoid dendritic cell response to toll-like receptor 9 activation","volume":"203","author":"Guiducci","year":"2006","journal-title":"J. Exp. Med."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1111\/imr.12109","article-title":"Immunity to viruses","volume":"255","author":"Braciale","year":"2013","journal-title":"Immunol. Rev."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"466","DOI":"10.1111\/j.1365-2567.2011.03412.x","article-title":"Regulation of effector and memory T-cell functions by type I interferon","volume":"132","author":"Huber","year":"2011","journal-title":"Immunology"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"498","DOI":"10.1038\/icb.2012.10","article-title":"Role of type i interferons in the activation of autoreactive b cells","volume":"90","author":"Kiefer","year":"2012","journal-title":"Immunol. Cell Biol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"492","DOI":"10.1038\/icb.2012.7","article-title":"Modulation of T-cell function by type i interferon","volume":"90","author":"Tough","year":"2012","journal-title":"Immunol. Cell Biol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"4279","DOI":"10.4049\/jimmunol.169.8.4279","article-title":"Coordinated and distinct roles for IFN-\u03b1 \u03b2, IL-12, and IL-15 regulation of NK cell responses to viral infection","volume":"169","author":"Nguyen","year":"2002","journal-title":"J. Immunol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1084\/jem.20051720","article-title":"Yellow fever vaccine YF-17D activates multiple dendritic cell subsets via TLR2, 7, 8, and 9 to stimulate polyvalent immunity","volume":"203","author":"Querec","year":"2006","journal-title":"J. Exp. Med."},{"key":"ref_42","first-page":"103","article-title":"Natural and vaccine induced immunity to fmd","volume":"288","author":"Doel","year":"2005","journal-title":"Curr. Top. Microbiol. Immunol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1080\/10495398.2014.902850","article-title":"Both foot-and-mouth disease virus and bovine viral diarrhea virus replication are inhibited by MX1 protein originated from porcine","volume":"26","author":"Shi","year":"2015","journal-title":"Anim. Biotechnol."},{"key":"ref_44","first-page":"11","article-title":"Production of transgenic pigs over-expressing the antiviral gene MX1","volume":"3","author":"Yan","year":"2014","journal-title":"Cell Regen Lond."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"2063","DOI":"10.1128\/JVI.01874-09","article-title":"Interferon-induced protection against foot-and-mouth disease virus infection correlates with enhanced tissue-specific innate immune cell infiltration and interferon-stimulated gene expression","volume":"84","author":"Moraes","year":"2010","journal-title":"J. Virol."}],"container-title":["Viruses"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4915\/7\/7\/2807\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T20:49:19Z","timestamp":1760215759000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4915\/7\/7\/2807"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,7,17]]},"references-count":45,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2015,7]]}},"alternative-id":["v7072807"],"URL":"https:\/\/doi.org\/10.3390\/v7072807","relation":{},"ISSN":["1999-4915"],"issn-type":[{"value":"1999-4915","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,7,17]]}}}