Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 109, Issue 36, Pages 14610-14615Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1212379109
Keywords
in vivo imaging; antiviral screening; flavivirus; interferon-stimulated gene
Categories
Funding
- National Institutes of Health [AI057158, AI091707]
- Green-berg Medical Research Institute
- Starr Foundation
- Ronald A. Shellow Memorial Fund
- National Institute of Diabetes and Digestive and Kidney Diseases National Research Service Award [DK082155]
- German Research Foundation
- Infectious Disease Society of America
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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.
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