NEURAMINIDASE AUGMENTS FC-GAMMA RECEPTOR II-MEDIATED ANTIBODY-DEPENDENT ENHANCEMENT OF DENGUE VIRUS-INFECTION

Antibody-dependent enhancement (ADE) of dengue virus infection occurs when neutralizing antibodies at sub-neutralizing concentrations or non -neutralizing antibodies form complexes with the virus. These virus-an tibody complexes can then attach to a Fcgamma receptor-bearing cell, v ia the Fc portion of the immunoglobulin, resulting in an increased num ber of infected cells. ADE may be responsible in part for the most sev ere clinical manifestations of dengue virus infection which include ha emorrhage and shock. Three classes of human Fcgamma receptors exist, F cgammaRI, FcgammaRII and FCgammaRIII. In this study, we examined the e ffects of neuraminidase on ADE of dengue virus infection mediated by t he low-affinity FcgammaRII. K562 cells, which express only FcgammaRII, treated with neuraminidase resulted in augmentation of ADE of dengue virus infection by human anti-dengue antibodies. This augmented ADE of infection could be blocked by anti-FcgammaRII monoclonal antibody IV. 3. Incubation of neuraminidase-treated K562 cells with IgG-coated hum an red blood cells resulted in an increase in the percentage of rosett e formations compared with the untreated K562 cells. A bispecific anti body directed against FcgammaRII and dengue virus (IV. 3 x 2H2) enhanc ed virus infection. Neuraminidase also augmented ADE mediated by this antibody, but to a much lesser degree (by 50%) compared with that seen using conventional human anti-dengue antibody (by 200 to 300%). Fluor escence-activated cell sorting analysis of neuraminidase-treated K562 cells showed that the number of FcgammaRII-specific antibodies that bi nd to FcgammaRII increases by 15 to 20% after treatment with neuramini dase. These results indicate that neuraminidase augments ADE of dengue virus infection and that the augmented ADE is mediated through Fcgamm aRII.