Gamma interferon augments Fc gamma receptor-mediated dengue virus infection of human monocytic cells

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Abstract
It has been reported that anti-dengue antibodies at subneutralizing concentrations augment dengue virus infection of monocytic cells. This is due to the increased uptake of dengue virus in the form of virus-antibody complexes by cells via Fc.gamma. receptors. We analyzed the effects of recombinant human gamma interferon (rIFN-.gamma.) on dengue virus infection of human monocytic cells. U937 cells, a human monocytic cell line, were infected with dengue virus in the form of virus-antibody complexes after rIFN-.gamma. treatment. Pretreatment of U937 cells with rIFN-.gamma. resulted in a significant increase in the nunber of dengue virus-infected cells and in the yield of infectious virus. rIFN-.gamma. did not augment dengue virus infection when cells were infected with virus in the absence of anti-dengue antibodies. Gamma interferon ((IFN-.gamma.) produced by peripheral blood lymphocytes from dengue-immune donors after in vitro stimulation with dengue antigens also augmented dengue virus infection of U937 cells. IFN-.gamma. did not augment dengue virus infections when cells were infected with virus in the presence of F(ab'')2 prepared from anti-dengue immunoglobulin G. Human immunoglobulin inhibited IFN-.gamma.-induced augmentation. IFN-.gamma. increased the number of Fc.gamma. receptors on U937 cells. The increase in the percentage of dengue antigen-positive cells correlated with the increase in the number of Fc.gamma. receptors after rIFN-.gamma.treatment. These results indicate that IFN-.gamma.-induced augmentation of dengue virus infection is Fcy receptor mediated. Based on these results we conclude that IFN-.gamma. increases the number of Fc.gamma. receptors and that this leads to an augmented uptake of dengue virus in the form of dengue virus-antibody complexes, which results in augmented dengue virus infection.