Dengue reporter viruses reveal viral dynamics in interferon receptor-deficient mice and sensitivity to interferon effectors in vitro.
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.
Laboratory of Virology and Infectious Disease, Center for the Study of Hepatitis C, The Rockefeller University, New York, NY 10065, USA.
John W
JW
Schoggins
Marcus
M
Dorner
Michael
M
Feulner
Naoko
N
Imanaka
Mary Y
MY
Murphy
Alexander
A
Ploss
Charles M
CM
Rice
D000704:Analysis of Variance; D000818:Animals; D002522:Chlorocebus aethiops; D003715:Dengue / Q000503:physiopathology*; D003716:Dengue Virus / Q000235:genetics* / Q000378:metabolism; D005434:Flow Cytometry; D015723:Gene Library; D017930:Genes, Reporter; D005818:Genetic Engineering / Q000379:methods*; D049452:Green Fluorescent Proteins / Q000235:genetics* / Q000378:metabolism; D057166:High-Throughput Screening Assays / Q000379:methods*; D066298:In Vitro Techniques; D049409:Luciferases, Firefly / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D010957:Plasmids / Q000235:genetics; D014709:Vero Cells
D049452:Green Fluorescent Proteins; D049409:Luciferases, Firefly