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Dengue reporter viruses reveal viral dynamics in interferon receptor-deficient mice and sensitivity to interferon effectors in vitro
- Source :
- Proceedings of the National Academy of Sciences of the United States of America. 109(36)
- Publication Year :
- 2012
-
Abstract
- Dengue virus (DENV) is a global disease threat for which there are no approved antivirals or vaccines. Establishing state-of-the-art screening systems that rely on fluorescent or luminescent reporters may accelerate the development of anti-DENV therapeutics. However, relatively few reporter DENV platforms exist. Here, we show that DENV can be genetically engineered to express a green fluorescent protein or firefly luciferase. Reporter viruses are infectious in vitro and in vivo and are sensitive to antiviral compounds, neutralizing antibodies, and interferons. Bioluminescence imaging was used to follow the dynamics of DENV infection in mice and revealed that the virus localized predominantly to lymphoid and gut-associated tissues. The high-throughput potential of reporter DENV was demonstrated by screening a library of more than 350 IFN-stimulated genes for antiviral activity. Several antiviral effectors were identified, and they targeted DENV at two distinct life cycle steps. These viruses provide a powerful platform for applications ranging from validation of vaccine candidates to antiviral discovery.
- Subjects :
- viruses
Green Fluorescent Proteins
Dengue virus
In Vitro Techniques
medicine.disease_cause
Virus
Dengue
Mice
Interferon
Genes, Reporter
Luciferases, Firefly
Chlorocebus aethiops
medicine
Bioluminescence imaging
Animals
Luciferase
Vero Cells
Gene Library
Analysis of Variance
Multidisciplinary
biology
Interferon-stimulated gene
virus diseases
biochemical phenomena, metabolism, and nutrition
Dengue Virus
Biological Sciences
biology.organism_classification
Flow Cytometry
Virology
High-Throughput Screening Assays
Flavivirus
Vero cell
Genetic Engineering
medicine.drug
Plasmids
Subjects
Details
- ISSN :
- 10916490
- Volume :
- 109
- Issue :
- 36
- Database :
- OpenAIRE
- Journal :
- Proceedings of the National Academy of Sciences of the United States of America
- Accession number :
- edsair.doi.dedup.....4ac1e3651378f961ec1642c606cb1352