AN INVESTIGATION OF THE ROLE OF FC GAMMA RECEPTORS IN DENGUE VIRUS NEUTRALIZATION

Abstract

Dengue disease is a burden on most of the tropical nations and currently there is no licensed vaccine or therapeutic for it. In humans, dengue virus (DENV) has been shown to infect monocytes, macrophages and dendritic cells, which express activating Fc gamma receptors (FcyR). Consequently, neutralization of DENV by antibodies should be understood in the context of these cell types. Using cells expressing FcyRI and/or FcyRII, this thesis examined how different activating FcyRs influence the amount of antibody required to completely neutralize DENV. Experimental data indicates that the amount of antibody needed for complete DENV neutralization is significantly lower when immune complexes(IC) are phagocytosed by FcyRI than by FcyRIIA. Moreover, FcyRI is preferentially engaged by DENV when opsonized with neutralizing levels of antibody by clustering this receptor. Finally, we also show that lower antibody concentration required when DENV IC is phagocytosed by FcyRI instead of FcyRIIA cannot be explained by an antiviral response triggered by FcyRI signaling. Collectively, data from this thesis suggests that phagocytosis by FcyRI is a more efficient pathway for viral clearance.