Dengue reporter viruses reveal viral dynamics in interferon receptor-deficient mice and sensitivity to interferon effectors in vitro

John W. Schoggins, Marcus Dorner, Michael Feulner, Naoko Imanaka, Mary Y. Murphy, Alexander Ploss, Charles M. Rice

Research output: Contribution to journalArticle

91 Citations (Scopus)

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 firefl y 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.

Original languageEnglish (US)
Pages (from-to)14610-14615
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume109
Issue number36
DOIs
StatePublished - Sep 4 2012

Fingerprint

Interferon Receptors
Dengue Virus
Interferons
Antiviral Agents
Viruses
Vaccines
Virus Diseases
Green Fluorescent Proteins
In Vitro Techniques
Neutralizing Antibodies
Life Cycle Stages
Luciferases
Libraries

Keywords

  • Antiviral screening
  • Flavivirus
  • In vivo imaging
  • Interferon-stimulated gene

ASJC Scopus subject areas

  • General

Cite this

Dengue reporter viruses reveal viral dynamics in interferon receptor-deficient mice and sensitivity to interferon effectors in vitro. / Schoggins, John W.; Dorner, Marcus; Feulner, Michael; Imanaka, Naoko; Murphy, Mary Y.; Ploss, Alexander; Rice, Charles M.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 109, No. 36, 04.09.2012, p. 14610-14615.

Research output: Contribution to journalArticle

Schoggins, John W. ; Dorner, Marcus ; Feulner, Michael ; Imanaka, Naoko ; Murphy, Mary Y. ; Ploss, Alexander ; Rice, Charles M. / Dengue reporter viruses reveal viral dynamics in interferon receptor-deficient mice and sensitivity to interferon effectors in vitro. In: Proceedings of the National Academy of Sciences of the United States of America. 2012 ; Vol. 109, No. 36. pp. 14610-14615.
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