Paradoxical Role of Dengue Virus Envelope Protein Domain III Antibodies in Dengue Virus Infection.

Every year, approximately 100 million individuals are infected with dengue viral infections. Severe dengue infection, characterized as dengue hemorrhagic fever, leads to loss of intravascular fluids and severe bleeding. During dengue virus (DENV) secondary infection, the body produces neutralizing antibodies that cause a strong immune response, resulting in severe hemolysis and plasma leakage. DENV infections in humans stimulate production of virus serotype-specific and cross-reactive antibodies. The envelope (E) protein of DENV contains potent antigenic sites, with one known as E protein domain III (EDIII). Studies of DENV EDIII in mouse models have shown that strongly neutralizing mouse monoclonal antibodies (mAbs) are DENV-serotype specific and bind to an epitope on EDIII that is unique to each serotype. Unlike DENV-serotype-specific mouse mAbs, cross-reactive mAbs that bind to EDIII have moderate-to-weak neutralizing activity. Studies with mouse mAbs resulted in identification and mapping of different epitopes on the lateral ridge of DENV EDIII.