| Dengue virus (DENV) is the most common mosquito-borne viral infection in the world. It may cause disease ranging from mild febrile illness to devastating manifestations including Dengue hemorrhagic fever (DHF) and Dengue shock syndrome (DSS). There is good evidence to indicate that a prior heterosubtypic DENV infection may sensitize individuals for serious illness through a process of antibody-dependent enhancement (ADE) of disease. We propose to investigate the mechanism by which antibodies may either neutralize or enhance infection. Furthermore, we plan to investigate if immature dengue virus particles, and antibodies recognizing them, play an important role in Fc receptor uptake and ADE. We will use cell biology approaches, including single virus tracking in living cells, to address these fundamental question. We expect that the proposed project will provide new insights in disease pathogenesis and will provide guidance for the rational design of effective antibody-based therapeutics and efficacious vaccines that will protect against DENV infection without inducing immune enhancement. |
