Mouse models for dengue vaccines and antivirals

• Models of dengue infection in nonhuman primates and most mouse strains, including mouse–human chimeras, do not develop severe dengue disease.
• Interferon receptor-deficient mice can support DENV replication and develop severe dengue disease manifestations.
• Interferon receptor-deficient mice can be used as a stringent, in vivo challenge assay for evaluating certain antiviral and vaccine candidates.

Dengue virus (DENV) has substantial global impact, with an estimated 390 million people infected each year. In spite of this, there is currently no approved DENV-specific vaccine or antiviral. One reason for this is the difficulty involved with development of an adequate animal model. While non-human primates support viral replication, they do not exhibit signs of clinical disease. A mouse model is an ideal alternative; however, wild-type mice are resistant to DENV-induced disease. Infection of interferon receptor-deficient mice results in disease that recapitulates key features of severe dengue disease in humans. For the development of vaccines, interferon receptor-deficient mice provide a stringent model for testing vaccine-induced immune components from vaccinated wild-type mice.