The development of a compelling murine model of dengue virus (DENV) infection has been challenging, because DENV clinical isolates do not readily replicate or cause pathology in immunocompetent mice. However, research using immunocompromised mice and/or mouse-adapted viruses allows investigation of questions that may be impossible to address in human studies. In this review, we discuss the potential strengths and limitations of existing mouse models of dengue disease. Human studies are descriptive by nature; moreover, the strain, time, and sequence of infection are often unknown. In contrast, in mice, the conditions of infection are well defined and a large number of experimental parameters can be varied at will. Therefore, mouse models offer an opportunity to experimentally test hypotheses that are based on epidemiological observations. In particular, gain-of-function or loss-of-function models can be established to assess how different components of the immune system (either alone or in combination) contribute to protection or pathogenesis during secondary infections or after vaccination. In addition, mouse models have been used for pre-clinical testing of anti-viral drugs or for vaccine development studies. Conclusions based on mouse experiments must be extrapolated to DENV-infection in humans with caution due to the inherent limitations of animal models. However, research in mouse models is a useful complement to in vitro and epidemiological data, and may delineate new areas that deserve attention during future human studies.
Keywords: dengue, vaccines, mouse models, antibody-dependent enhancement, adaptive immunity
Citation: Zellweger RM and Shresta S (2014) Mouse models to study dengue virus immunology and pathogenesis. Front. Immunol. 5:151. doi: 10.3389/fimmu.2014.00151
Received: 31 January 2014; Accepted: 21 March 2014;
Published online: 10 April 2014.
Edited by:Scott B. Halstead, International Vaccine Institute, South Korea
Reviewed by:Lishan Su, University of North Carolina at Chapel Hill, USA
Copyright: © 2014 Zellweger and Shresta. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
*Correspondence: Sujan Shresta, Division of Vaccine Discovery, La Jolla Institute for Allergy and Immunology, 9420 Athena Circle, La Jolla, CA 92037, USA e-mail: firstname.lastname@example.org