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-antibody complexes can then attach to a Fc gamma receptor-bearing cell, via the Fc portion of the immunoglobulin, resulting in an increased number of infected cells. ADE may be responsible in part for the most severe clinical manifestations of dengue virus infection which include haemorrhage and shock. Three classes of human Fc gamma receptors exist, Fc gamma RI, Fc gamma RII and Fc gamma RIII. In this study, we examined the effects of neuraminidase on ADE of dengue virus infection mediated by the low-affinity Fc gamma RII. K562 cells, which express only Fc gamma RII, 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-Fc gamma RII monoclonal antibody IV.3. Incubation of neuraminidase-treated K562 cells with IgG-coated human red blood cells resulted in an increase in the percentage of rosette formations compared with the untreated K562 cells. A bispecific antibody directed against Fc gamma RII and dengue virus (IV.3 x 2H2) enhanced 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%). Fluorescence-activated cell sorting analysis of neuraminidase-treated K562 cells showed that the number of Fc gamma RII-specific antibodies that bind to Fc gamma RII increases by 15 to 20% after treatment with neuraminidase. These results indicate that neuraminidase augments ADE of dengue virus infection and that the augmented ADE is mediated through Fc gamma RII.
Mady
B J
BJ
Department of Medicine, University of Massachusetts Medical Center, Worcester 01655.
Kurane
I
I
Erbe
D V
DV
Fanger
M W
MW
Ennis
F A
FA
D000911:Antibodies, Monoclonal / Q000276:immunology; D000914:Antibodies, Viral / Q000276:immunology / Q000378:metabolism*; D003716:Dengue Virus / Q000276:immunology / Q000502:physiology*; D006801:Humans; D009439:Neuraminidase / Q000378:metabolism*; D017455:Receptors, IgE / Q000276:immunology / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D014779:Virus Replication
D000911:Antibodies, Monoclonal; D000914:Antibodies, Viral; D017455:Receptors, IgE; D009439:Neuraminidase