Of Mice and Men: Characterizing Dengue Virus Infection in Tissue Specific STAT1 Knockout Mice

Abstract

Dengue Virus (DENV) is a positive sense RNA virus with four serotypes and transmitted via Aedes aegypti and Aedes albopictus mosquitos. Over half of the world’s population is at risk for contracting DENV, which has symptom severity manifesting anywhere from flu-like symptoms to hemorrhagic fever and death. Secondary, heterologous infection is particularly concerning because no cross-protection exists between serotypes and disease symptoms during secondary infections are often more severe. There are no specific treatments for Dengue Virus infection, though promising steps have been made towards developing a tetravalent vaccine. Study of the complex biology of Dengue disease as well as the development of more effective therapies has been hampered by the lack of a suitable small animal model that faithfully recapitulates the human disease phenotype. In this paper we describe a series of assays and use them to characterize a novel model for DENV infection and pathology—mice that are STAT1 deficient within all hematopoietic cells. These mice are both susceptible and permissive to DENV infection and replication but show immunity when re-challenged with a homologous serotype. Serum isolated from VAV-Cre mice also shows elements of antibody-mediated memory protection. While we have started to characterize this model, more work must be done. Our long-term objectives are to define the barriers of Dengue species tropism and to develop a model system where Dengue can replicate in the presence of a fully competent immune system.