title: Gamma interferon augments Fc gamma receptor-mediated dengue virus infection of human monocytic cells.
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 number 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 Fc gamma 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.
authors: Department of Medicine, University of Massachusetts Medical Center, Worcester 01605.
authors: U
authors: U
authors: Kontny
authors: I
authors: I
authors: Kurane
authors: F A
authors: FA
authors: Ennis
mesh_terms: D000911:Antibodies, Monoclonal / Q000494:pharmacology; D000914:Antibodies, Viral / Q000502:physiology*; D000943:Antigens, Differentiation / Q000096:biosynthesis*; D002460:Cell Line; D003716:Dengue Virus / Q000276:immunology / Q000472:pathogenicity*; D006801:Humans; D007074:Immunoglobulin G / Q000502:physiology; D007371:Interferon-gamma / Q000276:immunology / Q000494:pharmacology*; D009000:Monocytes / Q000382:microbiology; D011961:Receptors, Fc / Q000096:biosynthesis*; D017452:Receptors, IgG; D011994:Recombinant Proteins; D005719:gamma-Globulins / Q000494:pharmacology
chemical_list: D000911:Antibodies, Monoclonal; D000914:Antibodies, Viral; D000943:Antigens, Differentiation; D007074:Immunoglobulin G; D011961:Receptors, Fc; D017452:Receptors, IgG; D011994:Recombinant Proteins; D005719:gamma-Globulins; D007371:Interferon-gamma