title: A Versatile Vector for In Vivo Monitoring of Type I Interferon Induction and Signaling.
abstract: Development of reporter systems for in vivo examination of IFN-β induction or signaling of type I interferon (IFN-I) pathways is of great interest in order to characterize biological responses to different inducers such as viral infections. Several reporter mice have been developed to monitor the induction of both pathways in response to different agonists. However, alternative strategies that do not require transgenic mice breeding have to date not been reported. In addition, detection of these pathways in vivo in animal species other than mice has not yet been addressed. Herein we describe a simple method based on the use of an adeno-associated viral vector (AAV8-3xIRF-ISRE-Luc) containing an IFN-β induction and signaling-sensitive promoter sequence controlling the expression of the reporter gene luciferase. This vector is valid for monitoring IFN-I responses in vivo elicited by diverse stimuli in different organs. Intravenous administration of the vector in C57BL/6 mice and Syrian hamsters was able to detect activation of the IFN pathway in the liver upon systemic treatment with different pro-inflammatory agents and infection with Newcastle disease virus (NDV). In addition, intranasal instillation of AAV8-3xIRF-ISRE-Luc showed a rapid and transient IFN-I response in the respiratory tract of mice infected with the influenza A/PR8/34 virus lacking the NS1 protein. In comparison, this response was delayed and exacerbated in mice infected with influenza A/PR/8 wild type virus. In conclusion, the AAV8-3xIRF-ISRE-Luc vector offers the possibility of detecting IFN-I activation in response to different stimuli and in different animal models with no need for reporter transgenic animals.
authors.affiliation: Gene Therapy and Regulation of Gene Expression Program, Center for Applied Medical Research (CIMA), University of Navarra, Pamplona, Spain.|IdiSNA Navarra Institute for Health Research, Pamplona, Spain.
authors.forename: Estanislao
authors.initials: E
authors.lastname: Nistal-Villan
authors.affiliation: Gene Therapy and Regulation of Gene Expression Program, Center for Applied Medical Research (CIMA), University of Navarra, Pamplona, Spain.|IdiSNA Navarra Institute for Health Research, Pamplona, Spain.
authors.forename: Joanna
authors.initials: J
authors.lastname: Poutou
authors.affiliation: Gene Therapy and Regulation of Gene Expression Program, Center for Applied Medical Research (CIMA), University of Navarra, Pamplona, Spain.|IdiSNA Navarra Institute for Health Research, Pamplona, Spain.
authors.forename: Estefania
authors.initials: E
authors.lastname: Rodríguez-Garcia
authors.affiliation: Gene Therapy and Regulation of Gene Expression Program, Center for Applied Medical Research (CIMA), University of Navarra, Pamplona, Spain.|IdiSNA Navarra Institute for Health Research, Pamplona, Spain.
authors.forename: Maria
authors.initials: M
authors.lastname: Buñuales
authors.affiliation: Gene Therapy and Regulation of Gene Expression Program, Center for Applied Medical Research (CIMA), University of Navarra, Pamplona, Spain.|IdiSNA Navarra Institute for Health Research, Pamplona, Spain.
authors.forename: Beatriz
authors.initials: B
authors.lastname: Carte-Abad
authors.affiliation: Gene Therapy and Regulation of Gene Expression Program, Center for Applied Medical Research (CIMA), University of Navarra, Pamplona, Spain.|IdiSNA Navarra Institute for Health Research, Pamplona, Spain.
authors.forename: Jesus
authors.initials: J
authors.lastname: Prieto
authors.affiliation: Gene Therapy and Regulation of Gene Expression Program, Center for Applied Medical Research (CIMA), University of Navarra, Pamplona, Spain.|IdiSNA Navarra Institute for Health Research, Pamplona, Spain.
authors.forename: Gloria
authors.initials: G
authors.lastname: Gonzalez-Aseguinolaza
authors.affiliation: Gene Therapy and Regulation of Gene Expression Program, Center for Applied Medical Research (CIMA), University of Navarra, Pamplona, Spain.|IdiSNA Navarra Institute for Health Research, Pamplona, Spain.
authors.forename: Ruben
authors.initials: R
authors.lastname: Hernandez-Alcoceba
authors.affiliation: Instituto de Salud Tropical, University of Navarra, Pamplona, Spain.|IdiSNA Navarra Institute for Health Research, Pamplona, Spain.
authors.forename: Esther
authors.initials: E
authors.lastname: Larrea
mesh_terms: D000818:Animals; D001717:Birds; D000229:Dependovirus / Q000235:genetics / Q000502:physiology; D005260:Female; D017930:Genes, Reporter / Q000235:genetics / Q000502:physiology; D005822:Genetic Vectors / Q000235:genetics / Q000502:physiology; D006801:Humans; D009980:Influenza A virus / Q000276:immunology / Q000502:physiology; D007370:Interferon Type I / Q000502:physiology*; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D008647:Mesocricetus; D051379:Mice; D008810:Mice, Inbred C57BL; D009521:Newcastle Disease; D009522:Newcastle disease virus / Q000276:immunology / Q000502:physiology; D009976:Orthomyxoviridae Infections / Q000276:immunology / Q000503:physiopathology; D011401:Promoter Regions, Genetic / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology*
chemical_list: D007370:Interferon Type I; D008156:Luciferases