Sub-neutralizing concentrations of antibody to dengue virus (DENV) enhance DENV infection of Fc receptor-expressing cells. This phenomenon, referred to as antibody-dependent enhancement (ADE), has been hypothesized to be responsible for the severe form of DENV infection, including dengue haemorrhagic fever and dengue shock syndrome. To analyse further the mechanisms of ADE , this study introduced a series of cytoplasmic mutants into human FcRIIA. The mutated FcRIIA was then expressed on COS-7 cells to see whether these mutants could enhance DENV infection. Wild-type FcRIIA enhanced DENV infection, consistent with previous reports using FcR-positive monocytes. Disruption of the immune tyrosine activation motif (ITAM) in the cytoplasmic domain of FcRIIA or removing the sequences between the two ITAM regions eliminated ADE. These findings suggest that the specific structure of the FcRIIA cytoplasmic domain is essential for the ability of FcRIIA to mediate ADE.


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