The role of antibody in enhancing dengue virus infection

•We develop mathematical models of primary and secondary dengue virus infections.•We analyze the models using asymptotic analysis techniques.•We fit the secondary infection model to temporal dengue virus.•We make predictions on virus–host interactions that lead to increased disease severity. Dengue virus has four distinct serotypes whose cross-reactive immune responses contribute to increased disease severity following heterologous infections. It was proposed that non-protective cross-reactive antibodies may play a role in disease enhancement. In this study we develop a mathematical model of host–virus interaction and predict the mechanisms responsible for virus expansion and loss during primary and secondary dengue infections. We use the model to determine the role of cross-reactive antibodies during dengue fever and dengue hemorrhagic fever-inducing secondary infections, and then compare the model to published patient data. We predict that the cross-reactive antibodies interfere with the non-neutralizing antibody effects by reducing the phagocyte-mediated removal of antibody-virus immune complexes.