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A Versatile Vector for In Vivo Monitoring of Type I Interferon Induction and Signaling.
- Source :
-
PloS one [PLoS One] 2016 Mar 23; Vol. 11 (3), pp. e0152031. Date of Electronic Publication: 2016 Mar 23 (Print Publication: 2016). - Publication Year :
- 2016
-
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.
- Subjects :
- Animals
Birds
Dependovirus genetics
Dependovirus physiology
Female
Genes, Reporter genetics
Genes, Reporter physiology
Genetic Vectors genetics
Genetic Vectors physiology
Humans
Influenza A virus immunology
Influenza A virus physiology
Luciferases genetics
Luciferases metabolism
Mesocricetus
Mice
Mice, Inbred C57BL
Newcastle Disease
Newcastle disease virus immunology
Newcastle disease virus physiology
Orthomyxoviridae Infections immunology
Orthomyxoviridae Infections physiopathology
Promoter Regions, Genetic physiology
Interferon Type I physiology
Signal Transduction physiology
Subjects
Details
- Language :
- English
- ISSN :
- 1932-6203
- Volume :
- 11
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- PloS one
- Publication Type :
- Academic Journal
- Accession number :
- 27007218
- Full Text :
- https://doi.org/10.1371/journal.pone.0152031