Modelling the Host Immune Response to Mature and Immature Dengue Viruses

Abstract

Immature dengue virions contained in patient blood samples are essentially not infectious because the uncleaved surface protein prM renders them incompetent for membrane fusion. However, the immature virions regain full infectivity when they interact with anti-prM antibodies, and once opsonised virion fusion into Fc receptor-expressing cells is facilitated. We propose a within-host mathematical model for the immune response which takes into account the dichotomy between mature infectious and immature noninfectious dengue virions. The model accounts for experimental observations on the different interactions of plasmacytoid dendritic cells with infected cells producing virions with different infectivity. We compute the basic reproduction number as a function of the proportion of infected cells producing noninfectious virions and use numerical simulations to compare the host’s immune response in a primary and a secondary dengue infections. The results can be placed in the immunoregulatory framework with plasmacytoid dendritic cells serving as a bridge between the innate and adaptive immune response, and pose questions for potential experimental work to validate hypothesis about the evolutionary context whereby the virus strives to maximise its chance for transmission from the human host to the mosquito vector.