Animal models for studying dengue pathogenesis and therapy

• Good in vivo models of dengue disease are needed to study pathogenesis and test new antiviral therapies.
• Experimental human infection is the most realistic model, but cannot include vascular leak and shock seen in severe dengue.
• Macaques generally develop low viremia and few signs of illness, but marmosets show more features of human disease.
• Humanized mice permit the study of humoral responses to infection, but have not yet reproduced severe dengue.
• Mice lacking a Type I interferon response are currently the best small animal model for testing new drugs against dengue.

Development of a suitable animal model for dengue virus disease is critical for understanding pathogenesis and for preclinical testing of antiviral drugs and vaccines. Many laboratory animal models of dengue virus infection have been investigated, but the challenges of recapitulating the complete disease still remain. In this review, we provide a comprehensive coverage of existing models, from man to mouse, with a specific focus on recent advances in mouse models for addressing the mechanistic aspects of severe dengue in humans. This article forms part of a symposium in Antiviral Research on flavivirus drug discovery.