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.
journal_name
Proc Natl Acad Sci U S Aauthors
Schoggins JW,Dorner M,Feulner M,Imanaka N,Murphy MY,Ploss A,Rice CMdoi
10.1073/pnas.1212379109subject
Has Abstractpub_date
2012-09-04 00:00:00pages
14610-5issue
36eissn
0027-8424issn
1091-6490pii
1212379109journal_volume
109pub_type
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