Dengue fever is a mosquito-borne tropical disease caused by the dengue virus (DENV). Antibody-dependent enhancement (ADE) was thought to be the mechanism through which DENV infectively propagate itself and infect more immune cells leading to the development of dengue fever (Guzman & Vazquez, 2010). FcγR mediates DENVAb complex binding to the host’s immune cells thus facilitates DENV infection through ADE. The cross-reaction of activating FcγRs by DENVAb complexes results in an activating intracellular signalling cascade through the phosphorylation of immunoreceptor tyrosine based activating motifs (ITAMs) of the cytoplasmic or γchain domain of FcR. The Fcγ receptors attach the DENVAb complexes to mononuclear phagocytes, thus enhancing the efficiency of infection and thereby increasing the number of infected mononuclear phagocytes (Smith and Clatworthy, 2010). Studies have shown that cytoplasmic domain immunoreceptor tyrosine based inhibitory motifs or immunoreceptor tyrosine based activating motifs (ITIM or ITAM) of the receptor plays the central role in the infectivity of dengue virus and subsequent development of fever. In a genetic swapping experiments, it was demonstrated that respective cytoplasmic domains of activating FcγRIIa and inhibitory FcγRIIb largely determine DENVADE (Boonnak et al., 2013).
Therefore, the major determinant for the effective function of Fc(ɣ)gamma receptor is dependent on the component of its cytoplasmic domain.
KEY WORDS; Fcɣ receptor, Antibody-dependent enhancement, Dengue virus, Cytoplasmic domain.